Introduction

In the majority of patients with epilepsy, seizures can be well controlled with appropriate medication. However, current estimates indicate that 20 - 30% of patients with epilepsy are refractory to all forms of medical therapy. These medically intractable patients are candidates for surgical treatment in an attempt to achieve better seizure control. Another group of patients who might benefit are those whose seizures may be relatively well controlled but who have certain characteristic presentations or lesions that strongly suggest surgical intervention might be curative. Overall, the single most important determinant of a successful surgical outcome is patient selection. This requires detailed presurgical evaluation to characterize seizure type, frequency, site of onset, psychosocial functioning and degree of disability in order to select the most appropriate treatment from a variety of surgical options.

Definitions

There are many types of seizures and different forms of epilepsy. A seizure is defined as a paroxysmal, self-limited change in behaviour associated with excessive electrical discharge from the central nervous system. Epilepsy is defined as a condition of recurrent seizures and medical intractability as recurrent seizures despite optimal treatment under the direction of an experienced neurologist over a two to three year period.

In the past, seizures have been classified based upon their clinical manifestations which had some relevance for patients and physicians but was of limited diagnostic or prognostic value. According to this classification, an epileptic disorder is defined as either being generalized, partial (focal) or undetermined.

 Primary generalized seizures start as a disturbance in both hemispheres synchronously without evidence of a localized onset. The manifestations of these seizures tend to be major motor seizures of a tonic, clonic, tonic-clonic, myoclonic or atonic type. They also include minor events of the petit mal (absence) type.

 Partial forms of epilepsy start in a focal area of the brain and may remain localized without alteration of consciousness. These events are referred to as simple partial seizures and the symptoms vary with the area of the brain affected. If the event spreads and alters consciousness it is referred to as a complex partial seizure. If the event spreads further and leads to a major motor seizure it is referred to as a secondarily generalized seizure and may be quite difficult to distinguish from the primary generalized forms. Partial seizures often arise from the limbic structures of the temporal and frontal lobes but can occur from any cortical region and are often quite refractory to medical therapy alone. In general, patients with partial seizure disorders are the most amenable to surgical intervention.

A second classification divides the clinical epilepsies into idiopathic, symptomatic and syndromic forms based upon their presumed etiologies..

 Idiopathic forms include some of the generalized seizure types that may have familial patterns but without a prominent genetic component such as simple febrile convulsions of childhood.

Symptomatic forms are those caused by a recognized central nervous system (CNS) lesion. Included in this type are cases of known structural pathology, metabolic abnormalities or neurodegenerative processes.

 Syndromic forms include disorders that may be idiopathic or symptomatic but seem to follow a clear and predictable course. These include childhood and juvenile absence epilepsies, juvenile myoclonic epilepsy and the Lennox-Gastaut Syndrome. The ability to place a patient in one or another of the syndromic categories has the advantage of providing a basis for predicting long term prognosis.

 From a surgical point of view however, dividing the seizure types into either generalized or focal appears to be the most useful. This is because most surgical decisions are based upon defining those seizures that originate in one focal area of the brain and localizing that area as a prelude to resection.

Presurgical   Evaluation

The goal of epilepsy surgery is to identify an abnormal area of cortex from which the seizures originate and remove it without causing any significant functional impairment. The primary components of the presurgical evaluation includes a detailed clinical history and physical examination, advanced neuro-imaging, video-EEG monitoring, neuropsychological testing and assessment of psychosocial functioning.  The major surgical questions one hopes to answer with this evaluation are:

1) Are the seizures focal or generalized .

 2) If focal, are they temporal or extratemporal in origin.

 3) Is there a lesion associated with the seizures .

 4) If surgery is undertaken what functional deficits, if any, might be anticipated.

Clinical Features

The presurgical evaluation of a patient with medically intractable epilepsy begins with a complete history and physical examination. One attempts to classify the different kinds of seizures as well as the frequency, severity and duration of each type. The clinical semiology of these events can yield important localizing information to the experienced clinician. It is also important to determine the age of onset, response to treatment and familial tendency to seizures. The pregnancy and delivery history is helpful in assessing congenital or early acquired abnormalities. Other past medical history of significance would include a history of febrile seizures, head injury or intracranial infection. An assessment of the adequacy of medication trials must also be made to ensure that the patient is truly refractory to medical therapy. On examination, the clinician looks for obvious asymmetries of development compatible with an early structural CNS lesion and focal neurologic or cognitive abnormalities suggestive of acquired disease.

Neuro-imaging

Modern neuroimaging is crucial to surgical decision making. In the past, skull x-rays, ventriculograms   and computerized tomography (CT) scans demonstrated indirect evidence of cerebral pathology in the form of focal or diffuse atrophy or space-occupying lesions. Recently, magnetic resonance imaging (MRI) has replaced CT scanning as the imaging study of choice to evaluate patients with epilepsy. MRI is an extremely sensitive tool that can detect abnormalities of the brain with exceptional anatomical detail.  This has been especially true for detecting focal atrophy ( e.g. hippocampal atrophy ), indolent gliomas, cortical dysplasias, cerebral gliosis and small structural lesions of the neocortex. Functional imaging attempts to visualize alterations in cerebral metabolism using Positron Emission Tomography (PET) and Single Photon Emission Computerized Tomography (SPECT). These studies reveal epileptic areas as hypometabolic between seizures and hypermetabolic during seizures. Although they lack the spatial resolution of MRI, PET and SPECT can play an important role in the localization of abnormal cortex.  

Electroencephalographic (EEG) Investigation

Electroencephalographic (EEG) investigation remains the most important aspect of the presurgical evaluation. Analysis of unselected EEG activity between events (interictal ) or of specific activity during events (ictal ) can provide evidence of focal electrical dysfunction. While certain interictal EEG abnormalities (spike and slow wave complexes) can be of localizing value, it is considered extremely important to record the EEG with concommitant videotape during the spontaneous occurrence of the patient's events.

Neuropsychological Testing

Detailed neuropsychological testing is carried out to reveal specific focal or multifocal cognitive deficits that might be correlated with the neuroimaging and EEG. This testing may help in localizing an abnormal area of the brain but also serves as a comparison for post-surgical evaluation. An intracarotid amobarbital test is generally done as a prelude to surgery in order to lateralize language and memory function and to avoid neurocognitive deficits.

Psychosocial Assessment

Psychosocial evaluation is also extremely important to assess current level of functioning and to ensure realistic goals and attitudes are engendered in both the patient and their family prior to surgery.

Diagnostic Surgical Options

When a primary epileptogenic region or seizure focus is suspected but remains obscure despite appropriate neuro-imaging and scalp (non-invasive ) video/EEG recordings, some form of implanted (invasive ) electrodes may be indicated. Intracranial electrodes can be placed in areas not readily sampled by routine surface electrodes and can give more precise EEG information because of their proximity to discharging areas of the brain and the lack of movement/muscle artifact on the recordings. The diagnostic surgical options of implanted electrodes include epidural, subdural and intracerebral or depth electrodes.

Epidural electrodes

Epidural electrodes are used infrequently and generally only for lateralization and approximate localization of seizure onset. These electrodes are placed through tiny openings in the skull with the electrode contact resting on the dura to provide a high amplitude EEG signal without muscle or movement artifact. Because they do not penetrate the dura the risk of infection is minor.

Subdural electrodes

These electrodes are placed subdurally on the surface of the brain in the form of rectangular grids or linear strips with flat metal contact points mounted in flexible plastic. The grids require a craniotomy for placement and therefore are limited to unilateral application. The strip electrodes can be placed through burr holes over the lateral convexity or under the frontal or temporal lobes. The major advantage of subdural electrodes is that they do not penetrate cerebral tissue and can record from a relatively wide area of the cortical surface.

Intracerebral depth electrodes

Intracerebral depth electrodes can be placed stereotactically into deep cerebral structures with the aid of CT, MR and angiography. Most centers employ flexible electrodes with multiple contact points that are placed through small holes in the skull and secured with some form of cranial fixation.  Electrodes are usually targeted towards the amygdala, hippocampus, orbital-frontal and cingulate regions and may be inserted via a lateral or vertex approach. Depth electrode investigation is generally indicated for patients with bitemporal, bifrontal of frontal temporal seizures and can localize a focal area of seizure onset not possible with scalp recordings.

Surgical   Decision Making

If the information obtained during the noninvasive presurgical evaluation consistently points towards a single area of the brain as being the site of seizure onset, then the patient may be taken directly to surgery for resection of that area. If neuro-imaging demonstrates a well-characterized lesion ( i.e. unilateral hippocampal atrophy, cavernous angioma, focal cortical dysplasia, etc.) and is supported by the clinical features of the seizures then surgery may be reasonable without the general requirement for ictal EEG data.. However, if the data gathered from the clinical examination, imaging studies and noninvasive EEG evaluation are conflicting or disparities arise in the presumed localization of the seizure, then invasive intracranial monitoring is warranted.  

Therapeutic Surgical Options

Epilepsy surgery began as removal of gross structural lesions of the brain. With the addition of EEG data from preoperative and intraoperative recordings, areas of removal expanded to include tissue that was grossly normal in appearance but known to give rise to epileptiform activity. Small areas of resection were soon replaced by partial lobectomies and more extensive cortical resection. Newer Surgical options include Vagal Nerve Stimulation and Gamma Knife Surgery.

General considerations

The primary objective of most epilepsy surgical procedures is to accurately localize and then completely excise the epileptogenic region without causing cognitive or neurologic deficit. An important determinant of the risk of surgery is the relationship of the lesion to functionally important or "eloquent" brain regions because injury to these "eloquent" areas can cause irreversible neurologic impairment.

The newest method of localizing cortical function is with functional MRI. This powerful neuroimaging technique can create an anatomical and functional model of an individual patient's brain. By combining detailed anatomical information with precise physiological information, fMRI is capable of creating a structural and functional model of an individual's brain.

Other non invasive cerebral mapping techniques that have evolved to localize functionally important cortical areas are magneto-encephalography (MEG) and positron emission tomography (PET). Both can localize certain cortical functions non-invasively .

Lesionectomy

With the advent of MRI, many patients with recurrent seizures are now discovered to have small, previously unrecognized lesions such as cavernous angiomas, low grade astrocytomas, cortical dysplasias and areas of focal atrophy that are clearly the cause of their seizures. In general, if these are located in extratemporal sites, removal of the lesion and a small rim of surrounding cortex is often successful in controlling seizures. If lesions are located within the temporal lobe, lesionectomy along with temporal lobectomy is carried out including the mesial temporal structures in order to yield good results in 80% of cases.

Temporal resections

 The majority of temporal lobectomies, whether in the dominant or nondominant hemisphere, can now be safely performed under general anesthesia with or without electrocorticography. It is important that the mesial temporal structures are included in the removal. Since almost 80% of temporal lobe seizures originate in the mesial structures, several operative approaches have been designed to reduce the amount of temporal neocortex removed but still resect the amygdala and hippocampus.

Extra-temporal resections

Extra-temporal resections are much less commonly performed with the majority being carried out in the frontal lobe. En bloc standardized resections are not generally suitable and most surgeons guide their resections by detailed electrocorticography, both intra- and extra-operatively along with detailed cortical mapping. Frontal resections range from localized topectomies to complete frontal lobectomies and must be carefully individualized.

Hemispherectomy

Hemispherectomy is another form of cortical excision that is limited to patients with congenital hemiplegia, chronic encephalitis, hemi-megalencephaly or Sturge-Weber syndrome. These patients tend to have severe epilepsy with wide spread independent epileptic discharges that often extend to the contralateral (normal) hemisphere. It is only performed on patients who have a dense hemianopsia and are already hemiplegic with no fine motor activity on the affected side.

     Corpus Callosotomy

Corpus callosotomy has been offered as an alternative to hemispherectomy in epileptic patients with congenital hemiplegia but the results are not as good as with hemispherectomy. It is indicated when the patient has a severely damaged hemisphere but motor, sensory or visual function that would be valuable to preserve. In general, however, corpus callosotomy is most useful for those patients with generalized seizure disorders and bilateral independent epileptic areas in the frontal region. The seizures that respond best to callosotomy are sudden falls or "drop attacks" with injury to the patient.

Multiple Subpial Transections

In patients with seizure onset or epileptic zones located in eloquent cortex, multiple vertical subpial transections have been recommended as an alternative to cortical resection. This technique leaves the vertical columnar arrangement of the cortex intact thereby preserving function but prevents spreading of the seizure discharge in the horizontal plane to reduce seizures.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) is an established treatment of medically refractory partial-onset seizures. Recent data from an open-label multicenter pilot study also suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. Despite the fact that surgery is needed to implant the stimulating device, the option of long-term use largely devoid of severe side effects would give this treatment modality a privileged place in the management of drug-resistant depression.

Vagus nerve stimulation is an effective, safe, and well-tolerated treatment in patients with long-standing, refractory partial-onset seizures, and may also be beneficial in other types of seizures  . However, data indicate that the effect of VNS may be delayed as long as a year and that patients continue to improve during that time.  Problems arising during the implantation procedure are rare and manageable. VNS might not be recommended to patients with cardiac conduction disorder and with sleep apnea.

Gamma Knife Surgery

The first radiosurgical treatments for epilepsy surgery were performed by Talairach in the 1950s; he implanted yttrium in patients with mesial temporal lobe epilepsies (MTLEs) and no space-occupying lesion. The patients had a high rate of seizure control, provided that the seizure foci were confined to the mesial structures of the temporal lobe.

 Gamma knife surgery can reduce or eliminate seizures in patients with medically refractory TLE. The treatment has a good level of safety.  Neuropsychological   testing   before and after radiosurgery shows no deterioration. Significant changes  occurs in the mesial temporal lobe at the time of maximal radiation effect, 1 year after treatment. Some   patients need corticosteroids during the period of maximal radiation-induced changes (9–14 months). The typical effect on seizures occurs at 9 to 12 months, just before the MRI changes.