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Surgery Insight: surgical management of epilepsy Ruben Kuzniecky* and Orrin Devinsky
S U M M A RY Epilepsy surgery has been shown to be an effective treatment for patients with intractable epilepsy. The only randomized controlled trial conducted in this setting to date found a dramatic advantage for surgery over medical treatment in temporal lobe epilepsy. In carefully selected patients, epilepsy surgery can control seizures, improve quality of life and reduce costs of medical care. Advances in diagnostic techniques are likely to improve patient selection, facilitate localization of epileptic foci and functional areas, and enable better prediction of outcomes. KEYWORDS epilepsy, intractability, morbidity, seizure focus, surgery
REVIEW CRITERIA MEDLINE was searched using OVID for articles published from 1987 to 2007. Search terms included “epilepsy surgery”, “epilepsy surgical techniques” and “epilepsy surgery prognosis”. Abstracts were reviewed and full articles were selected on the basis of relevance. We did not include personal communications or material only available in abstract form.
CME
Continuing Medical Education online Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. Medscape, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide CME for physicians. Medscape, LLC designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To receive credit, please go to http://www.medscape.com/cme/ncp and complete the post-test. Learning objectives Upon completion of this activity, participants should be able to: 1 Define intractable epilepsy and factors that increase resistance to medical treatment of epilepsy. 2 Describe preoperative studies for patients with epilepsy. 3 Describe the efficacy of surgery for epilepsy. 4 Identify the complications associated with surgery for epilepsy.
INTRODUCTION
R Kuzniecky is Professor of Neurology at New York University, and O Devinsky is Professor of Neurology, Neurosurgery and Psychiatry at New York University and Director of the New York University Comprehensive Epilepsy Center, New York, NY, USA. Correspondence *New York University Comprehensive Epilepsy Center, 403 East 34th Street 4th Floor, New York, NY 10016, USA
[email protected]
Epilepsy is a common neurological disorder that is estimated to affect 50,000,000 people worldwide.1 Despite major advances in recent years, epilepsy remains an extraordinary therapeutic challenge. Studies indicate that in one-third of patients with new-onset epilepsy, the seizures will become medically intractable, and more than 5,000,000 individuals worldwide are potential candidates for surgery.2 The effects of chronic uncontrolled epilepsy and multidrug therapy include progressive cognitive and behavioral declines, as well as increased accident and death rates.3,4 In carefully selected patients, epilepsy surgery can control seizures, improve quality of life, and reduce the costs of medical care.5 In this article, we will review the current surgical management of epilepsy, including the identification of candidates, methods for localization of the seizure focus, surgical techniques, and outcomes. THE INTRACTABLE EPILEPSIES
Received 11 July 2007 Accepted 18 September 2007
Epilepsy is defined as intractable when the disorder is disabling and not controllable with
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Box 1 Indications for epilepsy surgery. ■
Medical intractability (failure of two monotherapy drugs and a two-drug trial at the therapeutic level is generally considered to be adequate to define intractability)
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Single epileptogenic focus amenable to resection
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Absence of degenerative disease or nonepileptic seizures
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Focal epileptogenic structural lesion
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Surgically remediable syndrome (e.g. unilateral mesial temporal sclerosis, focal cortical dysplasia or hypothalamic hamartoma)
the recognition that certain epilepsy syndromes respond particularly well to surgery (Box 1). PATIENT SELECTION AND INVESTIGATIONS
standard therapies. Although patients with localization-related (partial) seizures of temporal lobe origin have been traditionally considered the group most likely to benefit from surgery, all seizure types and syndromes that become intractable should be viewed as potential surgical targets unless proven otherwise. The operational definition of medical intractability has evolved from one based on a specified period of medical failure (e.g. >2 years) or number of failed antiepileptic drugs (e.g. more than three) to encompass individualized, multidimensional criteria. These criteria can involve seizure symptoms and frequency, psychosocial impact, cognitive and behavioral consequences, and side effects. For example, simple partial seizures or occasional complex partial seizures that markedly impair quality of life fulfill the criteria for intractable epilepsy.6 Currently, two domains seem to have primary importance in the clinical definition of medical intractability: the rate of failure of tolerable antiepileptic drugs to control seizures, and the pathological substrate. Kwan and Brodie2 demonstrated in a sequential, open-label trial that 47% of patients with new-onset epilepsy became seizure-free on the first antiepileptic drug. Only an additional 13%, however, achieved seizure freedom with a second or third drug on monotherapy or polytherapy; in total, 40% of the patients eventually became medically intractable. Pathological substrates such as hippocampal sclerosis, brain malformation and penetrating head injury are predictive of medical intractability, and they are usually associated with good surgical outcome.7 This fact highlights the importance of early recognition of medical intractability and surgical candidacy. Other factors, such as early age at onset of epilepsy and developmental delay, are also associated with intractability.8–11 In summary, identification of medical intractability is now possible early in the disease course, and this process is encouraged by
674 NATURE CLINICAL PRACTICE NEUROLOGY
Surgical treatment of epilepsy is based on the concept that removal, lesioning or disconnection of a localized brain area that generates seizures will result in complete cessation of—or a reduction in—seizure activity.12 Several different diagnostic techniques can be used to determine the ictal generator and epileptogenic zone.13–16 Structural and functional imaging, neurophysiological techniques and psychological testing help to identify the seizure focus and functional areas. All centers use MRI and video–electroencephalogram (EEG) recordings, whereas other noninvasive (e.g. PET, single-photon emission computed tomography [SPECT] or magnetoencephalography [MEG]) and intracranial electrophysiological recordings and mappings are used to varying degrees at different centers and are often tailored to individual cases.17 Phase I investigations
Presurgical evaluation The neurological history and examination are carried out to identify any underlying disorder and to localize areas of dysfunction.18 Symptoms at seizure onset, during progression, and following a seizure can provide localizing clues. Skin examination can identify neurocutaneous syndromes.19–21 Neurological examination can also provide localizing features. Neurodegenerative disease and nonepileptic seizures are factors that often preclude epilepsy surgery.22–25 Electrophysiology Interictal and ictal scalp EEG recordings are critical determinants of surgical candidacy. Most centers require recording of at least two lateralized and localized seizures before a patient can be considered for surgery.14 Recordings of multiple seizures are required in some patients, especially when functional (e.g. interictal EEG) or imaging (e.g. MRI) data suggest more than one seizure focus.26 Focal interictal abnormalities and concordant ictal EEG and behavioral changes can provide sufficient localization for surgical intervention.27 Identification of a structural or other functional (e.g. PET) imaging abnormality consistent with electrophysiological data is, however, desirable before surgery is performed, especially if surgery without intracranial recordings is being contemplated.28,29
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A
B
C
Figure 1 Surgery for temporal lobe epilepsy. (A, B) Preoperative coronal MRI (T1-weighted and T2-weighted) showing left mesial temporal sclerosis. Note hippocampal atrophy and signal changes in the left hippocampus. (C) Postoperative coronal MRI (T1-weighted) showing left amygdalohippocampectomy. The patient has been seizure-free since surgery.
Neuroimaging Modern neuroimaging has had a major impact on the surgical management of epilepsy.17 A localized limbic or neocortical lesion on MRI correlates strongly with the seizure focus and with good surgical outcome.30,31 Some structural pathologies (e.g. arachnoid cysts and white matter lesions) are not associated with seizures. By contrast, hippocampal sclerosis, which can be detected by MRI with nearly 95% sensitivity, is highly epileptogenic, and is usually the cause of seizures in patients with temporal lobe epilepsy (TLE; Figure 1). Other lesions seen on MRI that can cause epilepsy include malformations of cortical development, benign developmental tumors and vascular malformations. High-resolution MRI at 1.5 T with tailored protocols might increase the yield of subtle lesions in surgical candidates by 30% relative to routine MRI.32 The ability of higher field magnets (3 T) to further increase the rate of detection of pathology in epilepsy is currently under study. Nuclear medicine studies include 2-fluoro-2[18F]-deoxy-d-glucose (FDG)-PET and interictal and ictal SPECT. FDG-PET is highly sensitive in TLE, but its yield is low in extra-temporal lobe epilepsy (E-TLE).33 If MRI and EEG abnormalities colocalize, FDG-PET is unlikely to contribute further to localization, although it remains a valuable procedure in TLE patients with a normal MRI scan.34 Magnetic resonance spectroscopy is an experimental procedure and is not routinely used to assess patients for epilepsy surgery.35–38 Functional MRI for language lateralization and localization is being used increasingly, although the sensitivity and specificity of this technique remain limited, especially in patients with bilateral language representation.39,40
Interictal SPECT has lower sensitivity for localization than does FDG-PET.41 Ictal SPECT with subtraction techniques can, however, provide unique localizing data in patients with normal MRI scans or with large or multiple lesions.41 The localizing value of ictal SPECT is tempered by logistical challenges or isotope availability (most hospitals do not have radioactive tracers available during non-peak hours), seizure duration (
