Background

Epilepsy is one of the most common neurologic diseases, with a worldwide prevalence of approximately 0.8%. In developing countries, antiepileptic drugs (AEDs) are the mainstay of treatment. Nevertheless, many patients with epilepsy never receive treatment that leaves them seizure free. Epilepsy surgery is underutilized in developed, and especially in developing countries, whether because of a lack of resources or because many physicians do not recognize that a treatable syndrome exists.

This article addresses some of the most common surgical procedures performed to treat epilepsy and explains the syndromes for which they are most useful. The type of evaluation required to prepare a patient for epilepsy surgery is discussed. Common procedures and imaging modalities used to aid in the diagnosis and localization of epilepsy before epilepsy surgery are also discussed. Advanced diagnostic techniques—in particular, intracranial electrode placement—are covered in some technical detail.

The following 4 operative procedures are presented as models on which a preliminary understanding of the various surgical strategies can be gained:

Anteromedial temporal resection (AMTR) - This is the most frequently performed operation for a common and well-described disorder—namely, medial temporal lobe epilepsy. It serves as a model for other focal resections.

Corpus callosotomy - This is the only surgical procedure that is applicable to generalized epilepsy syndromes.

Functional hemispherectomy (hemispherotomy)

Multiple subpial transection (MST) - This has limited applications and is being used less in recent years.

For patient education resources, see the Brain and Nervous System Center, as well as Epilepsy.

Reasons for considering surgical intervention

Although intracranial surgery involves inherent risks, these risks do not equal the risks of uncontrolled seizures. The morbidity and mortality of seizures include the following:

Accidental injury

Cognitive decline

Sudden unexplained death in epilepsy (SUDEP)

Psychological, social, and vocational impairment

Accidental injuries commonly include fractures, burns, dental injuries, lacerations, and head injuries. Cognitive decline and memory loss over time has been demonstrated to occur in patients with certain epilepsy syndromes who have recurrent convulsive seizures or episodes of status epilepticus.

Mortality rates for patients with nonconvulsive and convulsive seizures far exceed those for age-matched controls. Among patients with poorly controlled epilepsy, SUDEP can reach a rate of 1 death per 500 patients per year. Risk factors are poorly controlled seizures and low serum antiepileptic drug (AED) levels.

Both depression and anxiety are very common among patients with medically refractory epilepsy. Intractable epilepsy prevents driving, and reduces fertility and marriage rates. Vocational issues include inability to be employed or, if employed, underemployment.

The above factors clearly suggest that for certain forms of epilepsy, continued medical therapy after failure to control seizures with aggressive trials of AEDs is not optimal treatment. In several retrospective trials and 2 prospective, randomized, controlled trials for a well-defined syndrome with a known favorable surgical outcome (ie, mesial temporal lobe epilepsy), the efficacy of surgery significantly exceeds that of continued treatment with AEDs and the morbidity and mortality associated with surgical treatment has been demonstrated to be less than that associated with the disorder. [2, 3, 1]

In addition, surgery yields a better quality of life and reduced depression and anxiety as soon as 3 months after AMTR, compared with continued medical therapy. [3] This improved quality of life is specifically related to the occurrence of complete seizure freedom in both the medical and surgical study groups.

Criteria for surgical intervention

A candidate for epilepsy surgery must have not attained acceptable seizure control with sufficient trials of AEDs and must have a reasonable chance of benefiting from surgery. Adequate AED trials must be considered within the context of the patient’s circumstances and form of epilepsy. The precise numbers and types of AEDs that should be tried before surgery is recommended are unknown for the various epilepsy syndromes.

However, the American Academy of Neurology, the American Association of Neurological Surgeons, and the American Epilepsy Society have recommended the following practice parameters [1] :

Patients with disabling complex partial seizures, with or without secondarily generalized seizures, who have failed appropriate trials of first-line antiepileptic drugs, should be considered for referral to an epilepsy surgery center, although criteria for failure of drug treatment have not been definitely established (level A rating).

Patients referred to an epilepsy center for the reasons stated above who meet established criteria for an anteromedial temporal lobe resection and who will accept the risks and benefits of this procedure, as opposed to continuing pharmacotherapy, should be offered surgical treatment (level A rating).

In 1996, Engel emphasized that the strategy of trying all combinations of drugs is not an acceptable approach to patients with syndromes for which the chances of benefiting from surgical therapy are known to be excellent. [4] For example, with the advent of 9 completely new AEDs since 1993, an estimated 300 years would be required to try all medications in all combinations.

Far more important, subsequent studies of patients with new-onset seizures have shown that only 64% have seizure freedom by the time they try their third AED. [5] Thus, after 3 different AEDs have failed to control seizures, more than 35% of patients continue to have seizures. Therefore, the decision to proceed with surgery must take into consideration both the chance of seizure freedom with additional AED trials and the adverse long-term effects of uncontrolled seizures.

Strategy for surgical planning

Preoperative evaluation for epilepsy has changed substantially in the past few decades, most notably since the advent of long-term video-electroencephalographic (EEG) monitoring in the late 1970s, advanced neuroimaging, and subspecialty epilepsy centers. The preoperative evaluation requires input from many members of an integrated team, which includes neurologists, neurophysiologists, neuropsychologists, social workers, radiologists, nurses, and epilepsy neurosurgeons.

Key aspects of the evaluation include the patient’s history and physical examination findings, social circumstances, seizure syndrome and severity, and diagnostic testing. A surgical plan is usually developed at a multidisciplinary team conference. This allows open discussion among multiple experts so that the surgical approach is unique and is tailored to the individual’s personal needs and epilepsy syndrome.

When all preoperative information points to a unifying location and theory regarding focal seizure onset (also referred to as concordant data), then the patient may proceed directly to resective surgery. When data are inadequate to define a resective strategy, then diagnostic intracranial electrodes may be considered to further define the syndrome or site of seizure onset before any resective surgery.

The concept that epilepsy consists of a focus that can be removed has evolved into a more unified theory in which the neural network, environment, genetic predisposition, and epileptogenic substrate all must be considered during the evaluation of the patient with epilepsy, if surgery is to be effective. [6, 7]

Relevant Anatomy

The brain is composed of 3 main structural divisions: the cerebrum, the brainstem, and the cerebellum. At the base of the brain is the brainstem, which extends from the upper cervical spinal cord to the diencephalon of the cerebrum. The brainstem is divided into the medulla, pons, and midbrain. Posterior to the brainstem lies the cerebellum.

The cerebrum is the largest component of the brain. It is divided into right and left hemispheres. The left and right cerebral hemispheres are separated by the longitudinal cerebral fissure. The principal connection between the 2 hemispheres is the corpus callosum. Each cortical hemisphere can be divided into 4 lobes: frontal, temporal, parietal, and occipital. The frontal lobe can be distinguished from the temporal lobe by the lateral sulcus (Sylvian fissure). The frontal lobe can be distinguished from the parietal lobe by the central sulcus (Rolandic fissure). The parieto-occipital fissure, which is visible on the medial aspect of the hemisphere, divides the parietal and occipital lobes. Within the lateral sulcus is another cortical surface referred to as the insula.

The frontal lobe can then be further divided into the superior, middle, and inferior frontal gyri, which are divided by the superior and inferior frontal sulci, respectively. Similarly, the temporal lobe is divided into the superior, middle, and inferior temporal gyri, which are separated by the superior and inferior temporal sulci. Within the parietal lobe, the superior temporal sulcus is capped by the angular gyrus. Just above this, the lateral sulcus is capped by the supramarginal gyrus. Just below the angular gyrus, the lateral occipital gyrus caps the inferior temporal sulcus. See the image below.

Lateral and medial surfaces of cerebrum, showing major sulci and gyri. View Media Gallery

For more information about the relevant anatomy, see Brain Anatomy. See also Arteries to the Brain and Meninges, Central Nervous System Anatomy, and Facial Nerve Anatomy.

Indications

Anteromedial temporal resection

Indications for AMTR include the following:

Complex partial seizures with semiology typical of mesial temporal lobe epilepsy

Magnetic resonance imaging (MRI) evidence of unilateral hippocampal atrophy and increased T2-weighted signal (at some centers, volumetric measurements of the hippocampus are routinely obtained)

Unilateral temporal lobe hypometabolism on positron emission tomography (PET) scans if MRI findings are nonlesional in nature

EEG confirmation that seizures begin over the temporal area ipsilateral to the hippocampal atrophy or PET scan evidence of hypometabolism

Although AMTR for mesial temporal lobe epilepsy has now been shown to be more effective than continued medication, studies to date have included patients who have had epilepsy that has been refractory to medical treatment for a prolonged period. Most patients who are finally referred for AMTR have had epilepsy for approximately 20 years.

Currently, however, because continued complex partial and generalized tonic-clonic seizures have such negative effects on vocational, educational, social, cognitive, and psychological areas and because these seizures can cause injury and even sudden death, most epileptologists believe that AMTR should be offered to good surgical candidates earlier.

An issue that remains unclear is how much time must elapse, or how many AEDs must be found to be inadequate, before surgery is recommended. For this reason, the US National Institutes of Health sponsored a large prospective study, the Early Randomized Surgery for Epilepsy Trial (ERSET). ERSET was designed to compare AMTR against 2 additional years of aggressive AED management. The results of ERSET should help address this issue.

Corpus callosotomy

Aside from the requirement that the patient must experience medically refractory seizures, indications for corpus callosotomy have not been clearly defined. Moreover, in contrast with AMTR for complex partial seizures, there are no clear and consistent indicators that help identify patients likely to benefit from corpus callosotomy.

Overall, corpus callosotomy seems to lessen the frequency of primarily and secondarily generalized seizures (ie, tonic, clonic, tonic-clonic, and atonic seizures). Callosotomy significantly improves atonic seizures, but having atonic seizures does not guarantee that a patient will benefit from surgery. Complex partial seizures can be ameliorated somewhat, but the results are far more capricious.

Some epileptologists believe that people with epilepsy who have mental handicaps should not be considered for callosotomy, because it seldom renders patients seizure free and because these patients may benefit less than patients of normal intelligence. The presence or absence of mental handicaps is not a reliable predictor of outcome. The authors have personally observed gratifying results from callosotomy in patients with mental handicaps.

The goals of corpus callosotomy differ from those of resective surgery, in which a seizure-free outcome is more likely and expectations are higher. The usual aim of callosotomy is to reduce seizure frequency and associated morbidity. The additional goals of social or vocational rehabilitation, applicable to resective surgery, are often not realistic expectations after callosotomy.

Multiple subpial transections

The most effective surgical treatment of partial (focal) seizures has been removal of the seizure-producing cortex from the brain. However, this procedure cannot be performed if the seizure-producing cortex also serves an indispensable function, such as speech. Consequently, MST is the only acceptable surgical treatment of a focus within such cortex.

In 1989, Morrell et al reported on the use of MST to treat seizures from chronic (Rasmussen) encephalitis that affected the speech-dominant hemisphere. [8] The authors applied MST to speech and motor cortex and resected or disconnected the remainder of the hemisphere. Their results in these cases were not good, and they have since abandoned this indication.

In 1997, Patil et al reported on the application of MST to bilateral seizure foci in very difficult cases otherwise not considered for surgical intervention. [9]

MST has been used as surgical treatment of Landau-Kleffner syndrome (LKS), a form of acquired aphasia that is associated with epileptiform spiking (but not necessarily seizures) in the central neocortex.

Functional hemispherectomy

Functional hemispherectomy (often referred to as hemispherotomy in its current refined forms) is highly effective for treating epilepsy in well-selected candidates with catastrophic epilepsy. Candidates are persons who have injury and seizures limited to 1 hemisphere of the brain. Their seizures occur frequently enough to interfere with cognition and impair quality of life. The goal of surgery is to isolate the affected brain from the healthier hemisphere and thus allow the latter to function without the burden of seizures or interictal discharges. [10]

Most patients upon whom hemispherectomy has been performed have been children, though some previous reports include adults. [11] Etiologies of the catastrophic epilepsies leading to hemispherotomy include Rasmussen encephalitis, other encephalitides, prenatal ischemia (often with porencephaly), Sturge-Weber syndrome, cortical dysplasia, hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome, hemimegalencephaly, malignancy, and tuberous sclerosis.

Preferentially, the pathology is limited to a single hemisphere of the brain; recovery after surgical treatment depends on the remaining hemisphere’s ability to take over cognitive and language functions that may have previously been within the domain of the injured hemisphere.

Delaying surgery can lead to a decline in cognitive ability; accumulating evidence suggests that seizures themselves may delay cognitive development. [12, 10] The timing of surgery depends upon the severity of the seizures, the natural history of the illness affecting the patient, and the response to antiepileptic drug treatments.

When the syndrome presents early in life, many centers recommend proceeding with surgery rapidly to avoid loss of cognitive abilities due to an epileptic encephalopathy, which may impair learning and cognition. [13, 14, 15] When it presents later in life, the timing of surgery can be more controversial. However, there is evidence that patients with late-onset syndromes can respond to surgery with improvements in neurologic function as well, suggesting that plasticity after hemispherectomy is not limited to early childhood. [16]

Classification and Preoperative Diagnosis of Epilepsy

A preoperative diagnosis is made after a classification of the patient’s seizure types and specific epilepsy syndrome. The International League Against Epilepsy (ILAE) recognizes approximately 10 types of recurrent seizures and approximately 40 forms of epilepsy syndromes. Both classification schemes are based on the idea that seizures and epilepsies naturally fall into 2 major groups, based on the site of seizure onset in the brain: (1) partial (focal, localization-related) and (2) generalized. [17, 18]

The signs and symptoms (semiology) experienced by the patient and the EEG pattern recorded at ictal onset determine the seizure diagnosis. This process begins by recording a careful history. For example, an event that is initiated with a blank stare and arrest of motion and then progresses to the development of automatisms (ie, automatic repetitive semipurposeful movements) is likely a complex partial seizure.

For initial AED therapy, a presumptive diagnosis based on the history may suffice. Even under the best circumstances, however, a diagnosis based solely on the history can be incorrect. Therefore, when surgical therapy is being considered for intractable epilepsy, the most accurate way to determine the epilepsy syndrome diagnosis and brain location of seizure origin is to use long-term video-EEG (VEEG) monitoring.

The following is a simplification of the international classification of epileptic seizures:

Partial seizures (seizures that begin locally) - These include (1) simple partial seizures (consciousness not impaired; SPS), (2) complex partial seizures (consciousness impaired; CPS), and (3) partial seizures that secondarily progress to generalized tonic-clonic seizures (SGTCS).

Generalized seizures (seizures that arise diffusely) - These include absence seizures, atypical absence seizures, clonic seizures, tonic seizures, tonic-clonic seizures, myoclonic seizures, and atonic seizures.

Unclassified seizures

An epilepsy syndrome diagnosis combines the seizure type with its associated MRI, physical examination, genetic, and other features. For example, if a seizure (1) has correlative EEG epileptiform patterns (interictal spikes or sharp waves) and ictal discharges over the right temporal lobe, (2) occurs in a patient who had a febrile seizure as a child but no family history of epilepsy, and (3) is associated with ipsilateral atrophy and increased signal of the hippocampus on an MRI, it is likely a complex partial seizure of right mesial temporal lobe epilepsy.

The greatest value of a syndrome diagnosis is to provide a prognosis. In the above example, if the patient is right-handed with normal intelligence, he or she has excellent odds of becoming seizure free after right-sided AMTR.

A simplification of the previous international classification of the epilepsy syndromes has been proposed. [19, 18]

Focal (partial, localization-related) syndromes include the following:

Idiopathic (some are hereditary) - Benign childhood epilepsy with centrotemporal spikes, childhood epilepsy with occipital paroxysms, autosomal dominant nocturnal frontal lobe epilepsy, and familial temporal lobe epilepsies

Symptomatic (to known cause or lesion) - Temporal lobe epilepsies (mesial, lateral), frontal lobe epilepsies (several locations), parietal lobe epilepsies, occipital lobe epilepsies, and Rasmussen encephalitis

Generalized syndromes include the following:

Idiopathic (most are hereditary) - Benign neonatal familial convulsions, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, generalized epilepsy and febrile seizures plus, and various progressive myoclonic epilepsies

Symptomatic (or probably symptomatic) - West syndrome (infantile spasms) and Lennox-Gastaut syndrome

Mixed syndromes include continuous spike waves in slow sleep and acquired epileptic aphasia (Landau-Kleffner syndrome [LKS]). Special situations is also a category.

Structural and Metabolic Brain Imaging

Because seizures may result from cortical lesions or malformations, neuroimaging can often help identify and localize this damage and, therefore, the site of seizure onset. Imaging modalities include the following:

Skull radiography

Computed tomography (CT) scanning

MRI

PET

Single-photon emission tomography (SPECT)

Magnetoencephalography/magnetic source imaging (MEG/MSI)

Routine skull films are of little value in this setting. Routine CT scanning has largely been replaced by MRI because the latter provides superior images. The single exception to this generalization is that CT scanning demonstrates intraparenchymal calcium and acute bleeding better than MRI; this may be helpful in distinguishing certain types of tumors or central nervous system (CNS) syndromes (eg, tuberous sclerosis).

Brain MRI is unquestionably the best structural imaging study. Every surgical evaluation should include a complete brain MRI study with special thin-cut coronal magnified views perpendicular to the axis of the temporal horn. These views can demonstrate mesial temporal sclerosis.

Unlike MRI or CT scanning, PET scanning demonstrates brain glucose metabolism rather than structure. The typical finding from an interictal scan is hypometabolism in the region of the epileptic focus; if the scan is obtained during a seizure, the typical finding is hypermetabolism from the focus.

SPECT scanning helps visualize blood flow through the brain and, therefore, has been evaluated as another method for localizing the epileptic focus. Interictal SPECT scans are less accurate than ictal scans. However, ictal scans are problematic because the tracer must be injected within the initial seconds of seizure onset. This requires that the radionucleotide be available on the monitoring ward 24 hours per day along with personnel licensed (under state law) to administer intravenous injections.

Subtraction ictal-interictal SPECT co-registered to MRI (SISCOM) is a newer modality that is more accurate than either ictal or interictal SPECT scanning. Scans are obtained during an interictal period (at least 48 h apart, to accommodate radionucleotide washout) and within seconds of seizure onset. They are then subtracted from one another with specialized computer software. This method gives a better indication of the cortical area of ictal onset. The subtracted scan can then be co-registered onto the patient’s MRI to provide support for the location of the focus.

MEG/MSI is a noninvasive imaging technique that is based on the brain’s ability to produce small magnetic dipoles with neuronal discharges. Synchronous firing of large groups of neurons, as occurs in an interictal epileptiform discharge, creates a miniscule magnetic dipole that can be sensed with sophisticated imaging equipment and complicated computer analysis. This map of the epileptiform discharge can be useful for diagnostic purposes and for planning preoperative intracranial electrode placement.

Electroencephalographic Evaluation

EEG is the single most useful test in epilepsy diagnosis. An essential mistake is to place too much value on an isolated individual interictal recording. The assumption that a normal finding from the interictal scalp electrode EEG precludes the diagnosis of epilepsy is erroneous. The presence or absence of epileptiform discharges is highly variable, has no relationship to seizure frequency (for most epilepsies), and may be affected by AEDs. Thus, EEGs may have to be repeated several times before epileptiform discharges are observed.

By definition, epileptiform discharges are interictal patterns that include spikes, spike-and-slow-wave complexes, sharp waves, and sharp-and-slow-wave complexes. The reader should refer to the second international glossary of EEG terms for precise definitions. [20]

When the waking scalp EEG fails to demonstrate evidence of epilepsy but the diagnosis is still suspected, a sleep EEG is recommended. Epileptiform discharges commonly activate during non–rapid eye movement sleep in some epilepsies. On fewer occasions than in the past, sphenoidal and additional extracranial electrodes are used to help reveal epileptiform (interictal) and ictal discharges. [21]

Although the standard scalp EEG is helpful in making a diagnosis of epilepsy, it is not usually used when the physician makes major surgical decisions. This is because the distribution of interictal EEG discharges may not correctly localize epileptic foci. This error occurs for several reasons. First, discharges can be multifocal, although a single focus can be the origin of all seizures.

Furthermore, because the EEG consists of volume-conducted potentials that originate over a relatively large area of cortical gray matter, some discharges can shift apparent location within or between hemispheres, and others may appear widely or even diffusely over the scalp. In addition, to obtain the most accurate data possible, recording sufficient numbers of the patient’s typical seizures is important.

Like interictal discharges, ictal discharges vary somewhat. Also, more than 1 seizure focus or psychogenic or physiologic nonepileptic seizure may be found when numerous episodes are recorded. [22, 23] The latter may greatly affect a decision to proceed with surgery. Therefore, all surgical candidates should undergo long-term VEEG monitoring before surgery to record several typical seizures.

Features of the scalp EEG ictal discharge, other than just location, can be helpful in the preoperative evaluation. In 1 study, for example, the authors reported that the frequency of the initial ictal discharge in the scalp EEG correlated with the degree of hippocampal pathology in temporal lobe epilepsy. [24]

Combining EEG with functional MRI in patients with focal epilepsy may help localize the epileptic foci. [25]

Neuropsychological Testing

Neuropsychological testing, also known as neurocognitive testing, is the process of empirically testing an individual’s functioning across a variety of cognitive domains, including attention, concentration, language, visuospatial skills, verbal and visual memory, and executive abilities (ie, problem solving, organization, strategic planning), as well as personality and emotional functioning.

Neuropsychologists use a variety of standardized tests to assess all areas of cognitive functioning. An individual’s performance on these standardized tests is then analyzed against normative data, and their performance is compared with that of their peers and with what is expected on the basis of their estimated premorbid level of cognitive functioning. Patterns of cognitive strengths and weaknesses then provide information about brain-related deficits in cognitive functioning.

The idea that performance on specific neuropsychological tests is subserved by various areas of the brain is well established. For example, a right-handed individual’s performance on verbal memory tests (eg, story memory, verbal paired associates learning, and list-learning tasks) is largely subserved by left mesial temporal structures. [26] Similarly, a right-handed individual’s performance on visual memory tests (eg, figural memory and complex figure memory tasks) is largely subserved by right mesial temporal structures.

Thus, an individual’s cognitive strengths and weaknesses on neuropsychological testing can indicate areas of brain dysfunction, which provides additional information that can help localize an epileptogenic focus. [27] In addition, an individual’s cognitive strengths can provide information about possible cognitive risks involved in undergoing a neurosurgical resection to treat medically intractable epilepsy because a risk of increased memory deficits after resection of mesial temporal structures exists. [28]

Routinely, all epilepsy surgical candidates undergo extensive neuropsychological testing. Neuropsychological testing is tailored so as to best assess the type of epilepsy with which each individual presents, often focusing heavily on the area of cognitive functioning that likely has been most affected by a hypothesized epileptogenic focus. As a result, such testing often varies considerably from one patient to another.

Neuropsychological testing can also be used in nonoperative or postoperative epilepsy patients to assess their level of cognitive functioning and thereby assist with vocational and cognitive rehabilitation in the context of their neurologic disorder.

Intracarotid Amobarbital (Wada) Test

The intracarotid amobarbital test was developed by Jun Wada as a means of preoperatively determining which hemisphere contains language function. Although it is still used for this purpose, functional MRI for language now provides a noninvasive and more accurate way of lateralizing and localizing language functioning. The primary use of the Wada test is to assess language lateralization and the ability of the contralateral mesial temporal structures to support memory postoperatively when AMTR is being considered to treat medically intractable epilepsy.

The Wada test is conducted by individually cannulating each internal carotid artery. After contrast arteriography verifies that blood flows to the corresponding hemisphere and not to the brainstem or the contralateral side, a dose of sodium amobarbital (sufficient to impede hemispheric function) is injected. If the drug produces a contralateral hemiparesis, the function of that hemisphere is assumed to be minimized.

Language lateralization is determined by conducting a comprehensive screen of various components of language, including expressive language, receptive language, naming, repetition, and complex syntactical comprehension. If an individual is able to engage in all aspects of language while hemiparetic, language function is assumed to not be represented within that hemisphere.

Assessing a variety of aspects of language is important because some individuals possess a bilateral representation of language—that is, some aspects of language are subserved by one hemisphere, whereas other aspects of language are subserved by the contralateral hemisphere.

Memory functioning is assessed by presenting the patient with visual and auditory items (often using multiple sensory modalities to maximize the chance of encoding) while the hemisphere is anesthetized. After recovery of hemispheric function, which is confirmed by return of gross and fine motor function, as well as language if possible, the patient is then tested for free, cued, and recognition recall of the items with which he or she was presented during anesthetization.

If the patient can accurately recall 75% of the items presented during anesthetization, this provides evidence that the contralateral hemisphere should be able to support memory after AMTR of the hemisphere that was anesthetized. If the patient cannot accurately recall a sufficient number of items, this provides evidence that the patient may experience significant memory difficulties postoperatively.

Importantly, patients should undergo neuropsychological testing before undergoing a Wada test because neuropsychological testing provides important information about their baseline level of memory functioning and more accurately informs the results of the Wada test.

The deficiencies of this evaluation for memory function directly relate to the multiple problems of targeting a drug effect to specific brain structures via cerebral blood flow. Injection of a drug into the internal carotid artery does not assure drug effect in the basal temporal area in general or the hippocampal region specifically (an area that subserve memory function). This is due to variations in the direct blood supply to the hippocampus and inequalities in delivery when the drug is injected into the bloodstream.

Invasive Intracranial Monitoring

Intracranial EEG recording, also known as chronic electrocorticography (ECoG), is an invasive procedure that is performed when noninvasive preoperative evaluation has not led to definitive localization of a seizure syndrome and surgical plan. The preoperative team, which includes a neurosurgeon, a neurologist, a neuropsychologist, a social worker, and a neuroradiologist, considers all previous accumulated data to determine an appropriate strategy for placement of intracranial electrodes.

The following are examples of situations in which invasive intracranial monitoring may be required:

Seizures are lateralized but not localized (eg, a left-sided, widespread frontal-temporal onset).

Seizures are localized but not lateralized (eg, ictal EEG patterns that appear maximally over both temporal lobes).

Seizures are neither localized nor lateralized (eg, stereotyped complex partial seizures with diffuse ictal changes or initial changes obscured by artifact).

Seizure localization is discordant with other data (eg, EEG ictal scalp data are discordant with neuroimaging [MRI, PET, SPECT/SISCOM, MEG] or neuropsychological data).

The relation of seizure onset to functional tissue must be determined (eg, seizures with early involvement of language or motor function).

The relation of seizure onset to lesion must be determined (eg, dual pathology or multiple intracranial lesions).

Seizures are clinically suspected but VEEG is inadequate for defining them (eg, simple partial seizures with no detectable scalp EEG ictal discharge or suspected epileptic seizures with unusual semiology that suggests psychogenic seizures [pseudo-pseudoseizures]). [29]

Invasive intracranial monitoring is a diagnostic procedure that is designed to identify the site of ictal onset of seizures. Intracranial electrodes are reserved for the most difficult of cases; therefore, one risk is that the study will end up with a nondiagnostic result. The onus is on the surgeon to question where electrodes should be placed on the basis of the information available preoperatively and to consider what other alternative diagnosis should be included or excluded to obtain the best possible electrode placement.

Depth, strip, and grid electrodes are implantable intracranial devices used to record the ECoG over an lnger period and to stimulate the cortex to determine function. Any combination of these electrodes may be employed as necessary to answer the specific questions posed by the case history and presentation specific to a given patient, depending on the needs of the patient, experience of the monitoring team, and resources available for use.

Depth electrodes are multicontact, thin, tubular, rigid or semirigid electrodes that penetrate the brain to allow recording from deep structures. Strip electrodes are linear arrays of 2-16 disk electrodes embedded in a strip of Silastic, [30] (or they can be tubular, like depth electrodes). [31] Grid electrodes are parallel rows of electrodes that can be configured in standard or custom designs according to the surgeon’s preferences and the manufacturer’s capabilities. Grid and strip electrodes are designed to be in direct contact with brain neocortex.

In most cases, electrodes are placed in the subdural space, although they may occasionally be used in the epidural space. All of these electrode types are constructed from biologically inert materials (eg, Silastic, stainless steel, platinum). Platinum electrodes are more easily seen on fluoroscopic images than are stainless steel electrodes and are compatible with MRI so that postoperative diagnostic and localizing neuroimaging studies can be obtained.

Placement of strip electrodes

Strip electrodes are used most often to lateralize the side of seizure onset in frontal and temporal lobe epilepsy, but they may also be used to obtain survey studies over all cortical surfaces of the brain. They are usually implanted while the patient is under general anesthesia, according to the preoperative plan created by the epilepsy monitoring team.

Electrodes can be directed safely over long distances within the calvaria by surfing them over the brain with a gentle fluid pulse. Fluoroscopy is used to confirm placement before closure of the wound. The electrode wires are tunneled under the skin with a 13-gauge passing needle designed for that purpose (Ad-Tech Medical; Racine, Wis); to decrease the risk of infection, they exit the skin several inches away from the burr-hole incision.

Cerebrospinal fluid (CSF) may leak from around the electrode wires during the first 3 days after implantation. This leakage can be minimized if the scalp exit sites for the electrode tails are directed superiorly toward the vertex of the skull. The suggested risk of infection from a CSF leak differs from center to center; however, completely sealing the skin with a foreign body in place is difficult, and CSF leaks are not uncommon. Because of this, the dressing is changed as often as needed.

Some authors suggest placing a cable-retaining suture in the scalp, [32, 33] both to attempt to secure the electrode and to decrease CSF leakage. The lead author has not found this to be helpful in decreasing CSF leakage, and all electrode companies manufacture quick-release connectors designed to break apart easily if tugged.

Patients are monitored with electrodes in place in the monitoring unit for 2-7 days to record their typical seizures. Subdural strip electrodes are removed through the skin without an open surgical procedure by placing gentle traction on the electrodes with the patient under conscious sedation or general anesthesia.

Although strip electrodes can be inserted epidurally, [34, 35] this practice is not advisable for routine cases because the exposure is limited to the lateral convexities of the brain. The epidural space in the temporal fossa does not allow the electrode to be advanced medially enough to record from the parahippocampal gyrus, and electrodes cannot be placed over mesial frontal lobe cortex.

In most exploratory investigations, these locations should be sampled. However, epidural placement may be the most reasonable option when recording from a patient with a prior craniotomy because scarring may obliterate the subdural space.

Placement of grid electrodes

Arrays of electrodes more than 1 column wide are considered intracranial grids (see the image below). Practically speaking, electrode arrays that are 2-3 contacts wide cannot be easily passed for any substantial distance through a burr hole and require a craniotomy for placement.

Examples of various grid electrodes available for specific needs. These range in size and number of contacts. View Media Gallery

Once the decision to proceed with a craniotomy is made, grid arrays of 5-8 rows (20-64 contacts) are usually used to maximize coverage over the craniotomy site. The craniotomy site is determined based on data gathered during the preoperative evaluation; usually, a large craniotomy is performed to accommodate up to an 8 × 8-cm grid.

Prophylactic antibiotics and dexamethasone are routinely administered. Mannitol is not used unless necessary, because the putative space created by a fluid shift could adversely contribute to hematoma formation after closure.

Once placed, the grid is sutured to the dura to prevent motion. Often, 1 or more strip electrodes are added to sample adjacent areas or lobes (eg, the interhemispheric fissure or basal temporal lobe). The electrode tails of grids are tunneled in much the same way as strip electrodes (ie, toward the vertex) to prevent CSF leakage.

At some centers, the bone flap is frozen under sterile conditions until the patient returns to the operating room (OR) for grid removal. However, the author prefers to leave the bone flap in place to decrease the risk of hematoma formation at the craniotomy site.

After recovery in the postanesthesia care unit, the patient is transferred to the VEEG monitoring suite, where the patient is hooked up on the day of surgery and a formal head dressing is placed. Acute nursing care is provided in the monitoring suite for the first 24 hours after craniotomy, similar to the level practiced in a neurologic step-down unit. The grid is removed when sufficient data have been obtained to determine the site of ictal onset or, alternatively, to determine that more recording is not likely to lead to satisfactory localization.

If resective surgery is planned, the relationship of the grid to the underlying cortex must stay unchanged while the craniotomy is reopened. The dura is opened, with the grid-stabilizing sutures left intact and all relations between electrode contacts and unique underlying cortical topography (eg, blood vessels) left undisturbed. Once these relations have been documented and the surgeon has extrapolated the mapped data to the underlying cortex, the grid is removed and discarded.

Resective surgery is performed, with the neurophysiologist or pathologist present in the OR as necessary. If resection is not performed at the time of grid removal (eg, because of hemorrhage, edema, patient preference, or insufficient data), then pertinent landmarks may be documented with digital photography or frameless stereotaxy for reoperation at a later date.

Higher complication rates for intracranial grid electrode placement have been associated with an increased number of electrode contacts, increased length of the monitoring period, placement of burr holes in addition to the craniotomy, and multiple cable exit sites. [36, 37] At the authors’ institution, AEDs are stopped on the morning of surgery (except for benzodiazepines and barbiturates, which are given in reduced doses). VEEG monitoring continues until the epilepsy team believes that adequate ictal data have been obtained (usually within 2-8 days).

Placement of depth electrodes

Depth electrodes are used most commonly for recording from the hippocampus and amygdala. The approach preferred by the authors is to place electrodes via the occipital, parasagittal route. [38, 39] This trajectory allows simultaneous implantation into the amygdala and anterior and posterior hippocampus using a single multicontact electrode (see the image below).

Examples of 3 depth electrodes with varying numbers of contacts. Note that stylus is in place and is removed once electrode has been inserted. View Media Gallery

Placement is performed with either a frameless system or a stereotactic frame with adequate clearance at the back of the head. MRI is used with both frame-based and frameless stereotactic placement to allow direct visualization of the target and the trajectory. [31, 40, 41, 42, 43]

Indications for depth electrode placement are expanding as neuroimaging becomes more sophisticated and more complex epilepsy syndromes are identified. This is particularly true among the malformations of cortical development, particularly when the dysplastic lesion is subcortical. Depth electrode recordings into hypothalamic hamartomas and periventricular nodular heterotopia have shown ictal onsets beginning within the lesions, which subsequently spread to produce clinical seizures.

Depth electrodes are most often used in conjunction with other subdural strip or grid electrodes so that multiple brain areas are sampled simultaneously to avoid false localization based on insufficient data collection. Specific intracranial EEG ictal discharge frequencies, locations, and patterns can suggest, preoperatively, certain types of histopathologic findings. [44]

Completion of intracranial monitoring

At most epilepsy centers, rooms with hard-wired EEG and video telemetry instruments are used only for long-term monitoring, not for general medical or surgical patients. Patients may be taken directly from the recovery room to one of these monitoring rooms or may stay in the intensive care unit (ICU) for the first night of monitoring. Antiepileptic drugs are tapered or withdrawn, and VEEG recordings are begun on the day of electrode implantation.

The relative accuracy of ictal electrographic activity versus interictal activity remains somewhat controversial. In general, interictal spikes are usually more diffuse than the ictal onset zone, and bilateral interictal spikes can occur in patients who ultimately do well after a unilateral resection, and therefore, do not preclude a good surgical outcome.

Obtaining ictal recordings is usually preferable in order to confirm the significance of interictal abnormalities, in that ictal recordings are considered more accurate than interictal data. A possible exception to this general guideline might be when recording from a focal cortical dysplasia; distinctive interictal epileptiform patterns have been identified that may provide enough data to guide a resection based solely on interictal data.

In monitoring a lesion with intracranial electrodes, seizure outcome is best when both the lesion and the ictal onset zone are completely resected; outcome is compromised when either the lesion or the ictal onset zone is incompletely resected. [45, 46] In the case of nonlesional epilepsy, seizure freedom is more difficult to achieve, even in cases in which the ictal onset zone has been well studied with intracranial electrodes.

The number of seizures required to consider an intracranial study complete depends on the specific issues involved with treating a particular patient. In general, an arbitrary number of 3 typical clinical seizures has been considered the minimum number to be captured; however, exceptions to this rule abound. [47]

For example, a patient with a posterior temporal or parietal lesion and scalp EEG localization to the anterior temporal lobe that is delayed in comparison with the clinical onset might be considered for an intracranial study to confirm the clinical suspicion that seizures are falsely localized to the anterior temporal lobe. In such a case, 1-2 seizure onsets with intracranial EEG ictal onset directly over the lesion might yield sufficient data to allow the surgeon to proceed to surgical resection.

On the other hand, if a patient has nonlesional epilepsy and bilateral ictal onset over both temporal areas on scalp EEG monitoring, many more than 3 seizures would have to be recorded in order to exclude bilateral temporal onset or establish a predominant side of onset.

The type of ictal onset recorded may influence the number of seizures required. Fewer seizures must be recorded in patients who have identical ictal onset patterns over the exact same electrode contacts in every seizure. More seizures must be recorded in patients with multifocal ictal onsets over different electrodes from one seizure to another.

Initial ictal changes at the beginning of a seizure are more important than late changes and the propagation patterns of the seizure. Seizures that occur seconds to minutes after a previous seizure may be disregarded as being potentially misleading. [47, 48]

When intracranial monitoring is complete, most subdural strip and depth electrodes can be removed percutaneously in the OR after administration of a conscious sedation protocol or general anesthesia. Because of concern over contracting virally transmitted disease (eg, AIDS, Creutzfeldt-Jakob disease, hepatitis), recording electrodes are commonly discarded after a single use.

New computer-assisted prediction paradigms are being created to analyze ictal onset and changes in the background electrical state, interictal spike frequency, confluence analysis, and chaos theory in order to predict seizure occurrence minutes to hours before ictal onset. Intracranial monitoring will probably have to adapt in order to accommodate these new technologies in the near future. [49, 50, 51, 52, 53, 54, 55]

Repeat intracranial monitoring

The following are reasons why a second intracranial study might be considered [56, 57, 47, 58, 59, 60] :

Strip electrode survey study for lateralization and localization to a lobe, with a planned return at a later date for definition of the ictal onset zone and cortical mapping as necessary

Reimplantation of a second grid because of failed localization secondary to sampling error (seizures may occur on the margin of the grid, be diffuse, or show variable propagation that makes seizure localization uncertain.)

Recurrent seizures after a previous intracranial study and resection

A repeat intracranial study is typically performed months to years after the first intracranial study, either to give the wound time to heal or because seizures recur at some variable time after resective surgery. Often, an interim preoperative evaluation, which may include VEEG monitoring, ictal SPECT scanning, MRI, or MEG, is performed to reexplore the suspected cause of a person’s epilepsy and prepare a more effective intracranial study. Secondary grid implantations can be quite troublesome because dural adhesions are the rule rather than the exception.

Therefore, when planning a second intracranial study, the surgeon should anticipate a difficult entry and should use many of the strategies used for reoperation in other craniotomies, including enlarging the bone flap until pristine dura is encountered and opening the dura away from the previous operative site and away from functional cortex. If adhesions are encountered, an operating microscope should be reserved and used early in the dissection.

The authors routinely plan to spend 1-3 hours under the operating microscope when scheduling a reoperation for epilepsy. Even with tedious dissection, adhesions can limit the distal passage of electrodes and limit the effectiveness of a repeat intracranial study.

Several authors have suggested an alternative to delayed reoperation, [61, 62, 63] advocating immediate reimplantation during the same hospitalization if the findings from the first grid were not diagnostic. Doyle refers to this as a 3-stage procedure, and Lee describes the same technique as a double grid.

This technique has certain advantages over delayed return for implantation of a second grid. First, adhesions do not obscure the subdural space, which can limit grid reimplantation. Second, cortical injury can be avoided because adhesions do not need to be dissected from functional tissue. Third, intracranial EEG changes can be compared with the previous study while the subtleties of the previous intracranial ECoG are still fresh in the minds of the evaluating team.

Other authors, however, believe that placing a grid again immediately after a first operation is likely to alter the network of epileptogenesis and that resultant seizures with second grid implantation might not best represent the patient’s typical seizures.

Doyle advocates performing a limited resection of the ictal onset zone seen with the first grid, on the grounds that a partial resection of the epileptogenic region may help identify which additional areas are still contributing to seizure onset once the major site of ictal origin has been removed. Favorable seizure control was achieved with no apparent increase in surgical morbidity in 42 3-stage procedures compared with 369 traditional grid protocols [63] and in 18 double procedures compared with 165 routine intracranial procedures. [62]

Documentation of intracranial study

Each intracranial study is unique to the patient for whom it is designed. Even routine intracranial studies have subtle variations in electrode placement based on the patient’s anatomy. Some sort of documentation of the intracranial study is advisable for a number of reasons, including confirmation of the accuracy of placement, communication with the neurophysiology team, and correlation with gyral anatomy or intracranial lesions. Several documentation options, ranging from simple to complicated, are available.

When intracranial strip electrodes are used, the most vital part of the documentation of the study begins in the OR. As each electrode is inserted, the operating surgeon describes the identifying characteristics of that electrode (eg, length, color coding, scalp exit site) and its intracranial position to an assistant, usually an OR nurse, who documents this information directly in the operative record or chart notes so that no confusion is encountered when the electrodes are eventually connected.

Most EEG technologists appreciate a line diagram handwritten by the surgeon in the chart. This simple step can eliminate many potential sources of human error, particularly with extensive intracranial surveys, and facilitates communication between all members of the team.

Another simple way of documenting the operative technique is for the monitoring team to use an anatomic brain diagram and transparencies of the grid montage to create a mockup of the surgery. [64] The image created is compared with fluoroscopic images taken at surgery so that a relatively accurate rendition of the electrode placement is available within minutes on the day of the procedure. These images can be quite helpful in interpreting seizure onset and propagation during EEG monitoring.

In more complicated cases, a member of the monitoring team is present in the OR to take digital photographs of the exposed cortex before and after grid placement. Digital photography helps identify the relationship of a grid to the sylvian fissure and is one of the best methods of documenting the fine anatomy of the brain, including sulcal and arteriolar anatomy that cannot be seen with advanced imaging techniques.

More sophisticated imaging techniques have been developed and are being used with increasing frequency as advanced imaging software becomes more available. Cranial MRI with a head coil can be performed safely in patients with intracranial grids and strip electrodes in place if a few safety considerations are kept in mind.

Most electrode manufacturers endorse platinum electrodes as MRI compatible, although stainless steel electrodes have also been used without apparent patient injury. Because each epilepsy center has different procedures, it is advisable to check the recommendations of the particular electrode manufacturer before obtaining an MRI. In all cases, current loops can theoretically be created within a magnetic field if the electrode tails are allowed to contact one another. Therefore, all electrode tails should be isolated before performing MRI.

Most MRI workstations or software packages allow 3-dimensional reconstruction of images, which are often more useful than traditional MRIs or CT scans. [65, 66, 67] In addition, most frameless stereotactic navigation systems allow for image reconstructions of an MRI that can be merged with preoperative anatomic, functional, or angiographic imaging to create an accurate rendition of the grid in relation to relevant operative anatomy. [33, 67]

Cortical mapping

Often, in addition to defining the location of the epileptogenic cortex, the surgeon must determine its relationship to functional cortex. This requires mapping the cortex underlying an implanted grid electrode. [68, 69] The technique is similar to that employed in acute settings in the OR and requires a testing protocol appropriate to the cortical region being investigated.

Cortical stimulation is performed using commercially available constant-current generators. Cortical mapping is performed by selecting 2 adjacent electrodes (1-cm intervals) because bipolar stimulation provides more precise control of current flow. Bipolar pulses at 50 Hz are used for language, motor, and sensory mapping.

Extraoperative cortical mapping has several advantages over acute intraoperative mapping. Functional mapping may be performed in multiple sessions if necessary. For example, if a seizure that impairs function is generated during mapping, the patient may be allowed to recover for several hours (or days) until proceeding with further mapping. Advanced paradigms may be performed over hours or days that would not be possible in the acute intraoperative setting.

Once mapping is completed, the patient, family, and surgeon have time to discuss the potential risks and benefits of surgery and to make decisions to accept or reject a functional loss that might be associated with surgery.

During brain stimulation, brain mapping is performed by a neuropsychologist or physician, who may test language or motor function. A clinical neurophysiologist reviews the ECoG during stimulation to ensure that any disruption of neurological function is due to the stimulation and not an afterdischarge. Afterdischarge potentials are repetitive spike discharges or electrical seizures directly provoked by electrical stimulation and may limit the ability to map the brain or may lead to a seizure.

The amount of current needed to produce an effect varies from patient to patient and between cortical regions. Enough current should be used to produce a reliable effect without causing afterdischarge. Occasionally, pain can result from current spread to the dura or a nearby cortical vessel. In such cases, a particular contact may not be suitable for mapping.

Surgeons are often encouraged to be present for intracranial extraoperative mapping, particularly early in their careers. Some of the slight variations in mapping technique and interpretation have subtle ramifications for the surgeon and are different from those that a neurologist or neuropsychologist might appreciate. On some occasions, mapped cortical regions vary from what one would expect from classic anatomic studies, particularly in areas of cortical malformations. [70]

On other occasions, mapping different pairs of electrodes in a specific region (eg, motor or language areas) might allow the surgeon to appreciate the orientation of a crucial region relative to the orientation of the grid or to adjacent contacts. Finally, subtle errors in naming or language may be present extraoperatively, when the patient is off AEDs, and these errors may change when the patient is reloaded with AEDs. [71] Such subtleties of extraoperative mapping can be useful to the surgeon if observed personally before a resection.

Implanted grid arrays are excellent tools for identification of the position of sensorimotor cortex through somatosensory evoked potentials (SSEPs). Allison and colleagues have reviewed the rationale and technique, [71, 72, 73, 74] and others have discussed the clinical experience with subdural grids for this purpose. [68, 69, 75, 76, 77]

SSEPs can be used during acute recording in the OR, using subdural strip electrodes to identify primary motor cortex. The strip electrode must be positioned to traverse motor and sensory cortex, and it may have to be repositioned several times during intraoperative recording to optimize the signal. Therefore, if SSEPs are planned during extraoperative monitoring, using a subdural grid to increase the surface coverage by the electrode array is advantageous in order to optimize location of the motor cortex (see images below).

Craniotomy showing intracranial grid in place. Grid lies over left primary motor and sensory cortex, near vertex of skull. Patient is positioned laterally, and face is at right. Intracranial study was performed to document seizure onsets in patient who had previous oligodendroglioma removed. Seizures began just posterior to leg motor cortex, in primary sensory cortex. View Media Gallery

Primary motor cortex is located with use of extraoperative somatosensory evoked potentials and intraoperative cortical stimulation, as well as grid previously described (see above). Penfield instrument in field is positioned over primary motor cortex. View Media Gallery

Sometimes, extraoperative mapping indicates that the ictal onset zone is close to or overlies critical motor or speech areas. On such occasions, using the advantages of awake operative language mapping may be helpful at the time of grid removal and resection of the epileptic focus. Although extraoperative mapping has many advantages, the accuracy of its spatial resolution is limited to 1 cm, namely, the distance between 2 electrode pairs.

On occasion, awake intraoperative mapping helps confirm which electrode is the contact that directly overlies cortical function. This can be particularly important when the 2 electrodes span a sulcus; in such cases, awake mapping may allow the surgeon to determine which gyrus is involved in function and which gyrus is not. [75] In such cases, the epileptic zone may be resected up to the pial margin without disturbing function, as long as the vascular structures within the pia are preserved.

Complications of intracranial monitoring

In published series, infection rates from all types of intracranial electrodes range from 0-12%. The morbidity of the procedure depends on the type of electrode implantation; intracranial strip electrodes have the lowest morbidity, and intracranial grid placement has the highest morbidity. [30, 31, 32, 36, 37, 78, 68, 38, 41, 79, 80, 81, 82, 83, 84, 85]

The most common cause of morbidity in subdural strip placement is infection. One randomized study found a 0.85% rate of infection when preoperative antibiotics were given, compared with a 3% infection rate when no antibiotics were given. [83, 85] No difference in infection rates was noted between patients who received antibiotics for the duration of strip electrode implantation and those who received only a single preoperative dose; therefore, at the authors’ institution, a single dose of antibiotics is given immediately before strip or grid implantation.

Other complications of intracranial strip placement include cortical contusion, cerebral edema, brain abscess, subdural empyema and subdural hemorrhage, placement of electrodes into the brain parenchyma, accidental extraction of electrodes, and superficial wound infection. Many of these complications are minor and cause no long-term problems; permanent neurologic deficits are seen in less than 1% of patients who undergo intracranial strip electrode implantation.

Complications of grid implantation include infection, transient neurologic deficit, hematoma, cerebral edema with increased intracranial pressure, and infarction. Transient neurologic deficits can occur secondary to edema or hematoma associated with the grid. In most cases, if neurologic compromise is evident, the grid should be removed immediately.

Cerebral edema is more likely to occur with an increase in the duration of the monitoring session or with a greater number of intracranial electrodes. [36, 37] Some authors have been concerned that pediatric patients are more likely to develop increased intracranial pressure because, theoretically, less space is available to accommodate the mass of an intracranial grid [86] ; however, others have not found this to be a concern. [36, 87, 46, 88, 89]

Complications from depth electrodes include intraparenchymal hemorrhage, subarachnoid hemorrhage, arterial spasm, and misplacement of the electrode. The rate of permanent neurologic deficit from occipital depth electrode placement has been reported at less than 1%. [90, 91]

The risk of hitting the brainstem or posterior cerebral artery with occipitally inserted depth electrodes may be decreased by (1) targeting tip placement in the lateral amygdala and lateral hippocampus, (2) making sure the occipital burr hole is not too medial, and (3) confirming the trajectory with an image guidance system before electrode placement.

Alternatively, one can attempt to place the depth electrode into the lateral ventricle rather than into the hippocampus. To do so, a rigid guide cannula is placed into the ventricle (verified by identifying CSF flow from the cannula), and the depth electrode is placed into the ventricle. The electrode then lies in the temporal horn adjacent to the hippocampus, with its tip entering the targeted amygdala.

Ictal recording from the ventricle usually conducts signal well, with only occasional failure. [44] The signal obtained amplifies (1) both hippocampal and parahippocampal ictal onsets and (2) intraparenchymal amygdala onset. The risk of subarachnoid hemorrhage may be minimized if depth electrodes are placed under direct visualization through a burr hole rather than using a closed twist-drill technique, which helps avoid draining veins during placement, and by using image-guided stereotaxy and contrast-enhanced MRI to avoid surface veins at the entry point.

Some surgeons prefer orthogonal placement of depth electrodes, which has been facilitated by frameless stereotactic techniques. Several systems allow placement of orthogonal depth electrodes via twist drill or burr holes in the temporal fossa. Stereotaxy is required to avoid vascular injury to vessels of the middle cerebral artery and to gain accurate placement into the amygdala and hippocampus. Electrodes must be secured at the skin to ensure migration of the electrodes does not occur as the medial trajectory of these electrodes is towards the brainstem.

Formulation of Appropriate Surgical Strategy

Surgery may be considered as either definitive or palliative. Definitive surgery carries a significant chance of producing complete, or at least 70-90%, improvement in seizures. The goal of palliative procedures is to decrease seizure frequency, but rarely results in seizure freedom.

In general, definitive surgeries physically remove seizure-producing cortex from the brain. Examples are resections of small seizure-producing tumors, vascular abnormalities, cortical malformations, or lesions such as mesial temporal sclerosis. Palliative surgeries usually disrupt pathways involved in seizure production and propagation or attempt to disrupt seizures with the use of electrical stimulation; thus, the potential for continued seizures always remains.

General approach to epileptogenic lesions

Tumors that cause epilepsy are frequently low-grade astrocytomas, oligodendrogliomas, or gangliogliomas. Commonly, they are well circumscribed, and excellent outcomes can be achieved with a lesionectomy that includes the immediate surrounding abnormal cortex. [92]

However, there is a temptation to rush to surgery, on the assumption that the tumor must be causing the seizures. The more cautious epilepsy surgeon may consider the possibility of alternative diagnoses, such as dual pathology (eg, the presence of hippocampal atrophy and tumor in the same patient), or look for evidence for concomitant cortical dysplasia, depending on the suspected tumor pathology.

The preoperative evaluation in the setting of tumor pathology is to determine that the EEG findings and the tumor are not discordant, which can occur approximately 10-15% of the time. In such cases, the lesion may not be solely responsible for the epilepsy, and a more extensive resection may be required to control the epilepsy.

When the tumor and the lesion are concordant, the most common mistake in treating these tumors is to remove only the gross tumor and not the immediate surrounding tissue, thus leaving epileptogenic tissue in place and resulting in clinical seizure resumption. If seizures continue after tumor removal, it may be assumed that the tumor was not completely removed, regardless of whether MRI suggests a clean resection.

Small vascular abnormalities, such as cavernous hemangiomas surrounded by hemosiderin, can be extremely epileptogenic. Removal of the vascular abnormality and surrounding hemosiderin-stained cortex may be all that is necessary for an excellent seizure outcome in approximately 80% of patients, provided that the preoperative evaluation is concordant. [93]

Large vascular abnormalities (eg, high-flow arteriovenous malformations) are commonly associated with seizures. These abnormalities, unlike the smaller vascular lesions, do not always exhibit a clear relation between the structural lesion and the epileptogenic cortex, and simple lesionectomy often fails to stop the seizures.

Because of the technical difficulties involved, implanting a large grid electrode over these lesions for the purpose of mapping is usually not feasible. Therefore, treatment of such lesions should seldom be approached purely as epilepsy surgery. One successful approach is to stage surgical procedures; the vascular abnormality is removed with the intent of further investigation and possible surgery if seizures remain.

Epileptogenic congenital malformations of cortical development, such as cortical dysplasias, heterotopia, schizencephalic clefts, and the various forms of phakomatoses, are very difficult to treat surgically and usually necessitate more extensive evaluations and tailored resections based on data from implanted grid electrodes. [70] Seizure outcome after resection of such malformations is variable and directly relates to the complexity of the lesion.

Traumatic encephalomalacia is treatable surgically, with varied results. The difficulty with these lesions is that cortical damage may extend much further than the area of obvious anatomic damage or that multiple regions of the brain may be affected simultaneously.

Controversial issues in definitive surgery

With regard to performing an acute ECoG, some surgeons believe that epileptiform discharges recorded during surgery indicate which part of the brain is epileptogenic; therefore, these surgeons use the ECoG to define boundaries for cortical resections. [94] This approach is referred to as a tailored resection, in that no 2 operations are identical. Because anesthetics affect the reliability of acute ECoG recordings and prevent the surgeon from mapping cortical function (eg, language), tailored resections are performed best with the patient under local anesthesia.

Other surgeons believe that an acute interictal ECoG is not reliable enough to determine surgical boundaries and can be inaccurate; these surgeons proceed with a standardized operative approach, wherein tissue important for generating seizures is removed without considering the ECoG for some surgical procedures.

If there is a question that must be answered with ECoG, then the patient receives an intracranial study, long-term monitoring with intracranial electrodes is performed to capture ictal ECoG, and a tailored resection is done on the basis of intracranial ictal recording rather than short-term, less accurate, interictal data.

For AMTR, no scientific data support the belief that ECoG-guided resections produce better results than standard procedures do. A more rational view is that the surgical approach should be suited to the syndrome.

There are specific syndromes for which a standardized operation is very effective. The best example is complex partial seizures of mesial temporal lobe epilepsy with hippocampal sclerosis. Such patients have excellent seizure and language outcomes after standard surgical procedures done with general anesthesia. Likewise, excellent results can be expected from the removal of a well-circumscribed capillary hemangioma from a patient with complex partial seizures.

In contrast, patients with epilepsy secondary to other etiologies in other brain regions may need extensive cortical mapping and an ictal ECoG. In such cases, implantation of a large subdural grid electrode for long-term monitoring (with an ECoG) and mapping is preferred because it yields results superior to those obtained by performing an acute interictal ECoG.