Presurgical Evaluation for Epilepsy Including Intracranial Electrodes

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Chapter 108 Presurgical Evaluation for Epilepsy Including Intracranial Electrodes

Ana Luisa Velasco, Francisco Velasco, Bernardo Boleaga, José María Núñez, David Trejo

Medically Intractable Epilepsy

As many as 25% to 30% of epileptic patients fail to respond to adequate antiepileptic treatment.¹ Medically intractable (or refractory) epilepsy is commonly conceived as that which occurs when satisfactory seizure control cannot be achieved with any of the potentially available effective antiepileptic drugs (AEDs), alone or in combination, at doses or levels not associated with unacceptable side effects.² On the other hand, surgery has a success rate of about 75% (depending on the site of surgery, the type of surgery performed, and the underlying etiology).^3,⁴ In spite of this, surgical treatment of medically intractable epilepsy is often delayed or withheld. Referral for epilepsy surgery may take 20 to 25 years, resulting in a number of avoidable seizure-related deaths, including drowning, motor vehicle accident, fatal status epilepticus, and sudden unexpected death in eplilepsy (SUDEP).⁵ In children, appropriate timing for surgical procedures is critical, as lack of seizure control may interfere with consolidation of cognitive and motor functions in the developing brain.⁶

Other causes of poor response to medical treatment are noncompliance and presence of pseudoepileptic seizures alone or combined with epileptic ones, as well as incorrect classification of seizures and therefore incorrect pharmacologic treatment.⁷ Therefore, the first step in evaluating surgical candidates is to confirm that the proper diagnosis has been identified and to determine that appropriate medical treatment has been utilized.

Patients’ Perceptions

Patients’ satisfaction with achieved medical treatment results often depends on professional and social circumstances, as well as the type of seizures and the time of day in which they occur.⁷ Some patients seek surgical treatment for reasons other than medical intractability: intolerable side effects of AEDs, women who desire to get pregnant but are concerned about potential teratogenic medication effects, and avoidance of the social stigmata of the disease are some of the reasons patients express in requesting surgery. Self-assessment of quality of life is an important step in evaluating the patient’s perception of their disease. At our clinic, we use the questionnaires QOLIE-31 for adults^8,⁹ and QOLIE-48-AD for adolescents.^10,¹¹

Epilepsy surgery has three main goals: eliminate or decrease epileptic seizures, prevent neurologic deficit due to surgery, and improve the quality of life. In order to achieve these goals, a multidisciplinary team is required to solve the surgical questions: Where do the patient’s seizures start? Are there functional or eloquent areas involved? What is the prognosis after surgery? Answering these questions allows decisions regarding what type of surgery is indicated and how to customize the procedure to meet the patient’s needs. Currently, there are many diagnostic studies that can be performed, but it is important to remember that there is no single test that can be considered the gold standard for making a diagnosis or predicting the outcome. It is the clinician’s ability to correctly interpret and assess the quality and concordance between studies that usually leads to a correct diagnosis and successful surgery.¹² The diagnostic workup can be divided into noninvasive and invasive phases.

Phase 1 Testing: Noninvasive Studies

Clinical Diagnosis: Seizure Description

Probably the most important part of the noninvasive studies is the seizure description or semiology. This should lead to a preliminary hypothesis that can be tested and lead to the most probable diagnosis. Special attention should be paid to what both the family and patient report.

Specific auras have been described in different types of seizures. For example, the manifestations of fear and ascending epigastric sensation suggest a mesial temporal epilepsy; simple visual auras suggest an occipital focus; levitation, somatosensory areas; and sympathetic symptoms such as perspiration, difficulty in swallowing, and salivation to an insular focus.¹³

The sequence of symptoms that the patient has is also important; epigastric and psychic auras followed by behavioral arrest and automatisms (ocular, oral, hands, ambulatory) indicate a mesial temporal onset of seizures.¹⁴ A different sequence or visual, auditory, and somatic auras at the beginning point to extratemporal foci with propagation to the mesial temporal lobe.¹⁵ Dystonic positions of the hands as an initial symptom can implicate the contralateral frontal area. If these findings occur late in the seizure event, after behavioral arrest and automatisms, they lose their localizing precision. If a tonic clonic seizure occurs after auras or the symptoms previously mentioned, it is probably the result of propagation of a partial seizure, but if it is not preceded at all by any symptom, then the consideration of a primary generalized seizure should be entertained.

Postictal symptoms have to be taken into consideration; for example, if there is amnesia and sleeplessness for several hours, that suggests seizures of mesial temporal lobe onset. If, on the contrary, there is an immediate recovery, a frontal origin is more probable. Immediate post-ictal dysphasia can also indicate that the seizures may have come from the dominant hemisphere.

Interictal behavioral changes must also be explored since behavioral abnormalities such as perseveration and aggressiveness (frontal lobe symptoms), depression, anxiety, and memory problems (mesial temporal lobe symptoms), can orient toward a specific area. Together with the neuropsychology team, these findings can help design an appropriate set of tests for an individual patient.

Surface Electroencephalogram

The electroencephalogram (EEG) has been considered the most important test for diagnosis since its initial description. Indeed, when abnormal, the EEG provides valuable information:

Interictal Data

Focal discharges consisting of spikes and sharp waves, usually localized to the epileptic area, are suggestive of the focus location. If a focal discharge occurs at or near one of the electrodes common to two channels, one can observe a phase reversal, pointing to the focus localization. If a discharge occurs midway between two electrodes, each will be equipotential and the channel connected between them will not show an abnormality.

Some patients have bilateral secondary synchrony. This occurs when seizure activity starts in a cortical or mesial focus and spreads by the way of the thalamic reticular formation. A careful analysis will show that activity starts in a specific area and then spreads to other areas.

Ictal Data

Ictal recordings usually show acute and rhythmic theta activity, which starts in the affected region and afterwards propagates to other areas. The postictal activity can be slow and unilateral, indicating the affected hemisphere.¹⁶

A normal EEG does not mean that a patient does not have epilepsy; it is also true that the same patient might have different data in several EEG studies recorded on different days. The same patient can have a normal EEG one day, abnormal right-sided data another day, and contralateral data in another recording. This is part of the challenge in finding concordance.

Continuous Video/EEG Monitoring

This technique consists of recording simultaneously EEG as well as the behavior of the patient with a video camera for a period that can last up to several days.¹⁷ This method allows for confirmation of the clinical type of seizure and can correlate it with the onset of abnormal EEG activity, particularly ictal activity. It can also allow for the detection of cases with pseudoepileptic seizures.

Both EEG and video/EEG recordings have their limitations. In spite of the length of the registration period, sometimes seizures do not occur, or multiple movement or muscle artifacts do not permit proper visualization of EEG abnormalities. The spatial resolution is often not specific enough to permit the precise localization of the epileptic zone (EZ) and the clinical seizure type and EEG recording do not always coincide. In many of these cases, intracranial recording becomes necessary. Intracranial recordings can be used to lateralize (identify the side of seizure onset) and/or localize (identify the specific area within a hemisphere) the seizure focus.

Neuropsychological Assessment in Surgical Candidates

The overall objective of neuropsychological assessment in candidates for epilepsy surgery is to seek evidence of cognitive deficits and their relationship with other studies (clinical and electrophysiological).¹⁸^–²⁰

Neuropsychological testing answers specific questions that may impact the surgical decision. What is the patient’s overall neuropsychological status? Which is the hemispheric dominance for language? If cognitive deficits exist, are they lateralized? Is there concordance between neuropsychological findings and structural and electrophysiologic results? Is the patient at risk of a neuropsychological deficit from surgery, and what is the predicted degree of recovery?

There are specific tests for each of the above questions. We will focus on the second and third questions, with particular attention to adult patients with temporal lobe epilepsy.

Hemispheric Language Dominance

Determining the lateralization of language can have a significant impact in surgical planning. It has been established that 95% to 99% of right-handed subjects and 15% to 19% of left-handed have a left cerebral hemispheric dominance for language.^21,²² Due to the small percentage of subjects who may have a right hemisphere dominance, is very important to clarify each case.^23,²⁴ For example, a right-handed patient who presents with difficulties of language might be mistakenly classified as having a left hemisphere dysfunction when in fact he could have dysphasia of the dominant hemisphere, which is not necessarily the left.

For decades, the Wada test has been the gold standard for determining hemispheric language dominance (HLD).^21,²⁵^–²⁷ Recently, a growing number of publications report that other techniques such as functional magnetic resonance imaging (fMRI) may have the same degree of reliability,²⁷^–²⁹ without the disadvantages of cost, risk, and complexity of the technique.³⁰ New noninvasive techniques are evolving to substitute Wada test, however, they still present limitations.^21,^28,^29,³¹

To determine the HLD using fMRI, most authors use the task of evoking words silently, based on a semantic category (e.g., names of animals) to activate temporal regions,³² or a phonologic category (words beginning with the same letter) for activating frontal regions of the dominant hemisphere³³ (Fig. 108-1).

FIGURE 108-1 fMRI study showing left cerebral hemispheric dominance for language in a healthy subject using a phonologic category (see text).

The dichotic listening technique (DLT) has also been proved useful in determining the HLD.^34,³⁵ It consists of simultaneous presentation of two words (one in each ear) with the same characteristics in terms of sound, number of syllables and of common use, with the intention to present some competition for processing stimuli between the two hemispheres. With this methodology it has been shown that the majority of right and left-handed subjects have right ear advantages as a reflection of a left HLD.³⁴ Fig. 108-2 shows the variability in the index of HLD according to the dichotic listening test in right-handed healthy subjects. The lateralization index for language (LI) is a predictor of postoperative verbal memory deficit as shown by some studies.³⁶

FIGURE 108-2 Variability in language laterality in right-handed healthy subjects using the dichotic-listening test. The LI is obtained as follows: (L – R)/(L + R) = LI, where L = number of words heard with the left ear, and R = number of words heard with the right ear. A positive LI corresponded to a left-predominant lateralization and a negative LI corresponds to a right-predominant lateralization. B, bilateral representation (+0.25 to –0.25); LI, laterality index; SLL, strong left lateralization (+0.50 to +1); SRL, strong right lateralization (–0.50 to –1); WLL, weak left lateralization (+0.25 to +0.50); WRL, weak right lateralization (–0.25 to –0.50). (Redrawn from Lehéricy S, Biondi A, Sourour N, et al. Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations. Radiology. 2002;223(3):672-682.)

Lateralization of Memory Deficits

Lateralization of memory deficits (LMD) is another objective of preoperative neuropsychological assessment. Table 108-1 ³⁷ presents some of the available memory tests. At our clinic, we use the Battery of Learning and Memory and the Visuospatial Learning and Memory tests. When evidence is found for a memory deficit in the same hemisphere where the epileptic zone has been localized through clinical, EEG, and imaging data, the decision for surgery is strengthened; otherwise, the complete testing described in Table 108-1 is applied. Evaluation of memory is performed by well-established tests that vary slightly from one center to another.³⁷ In approximately 50% of patients it is not possible to determine the lateralization of memory deficit through neuropsychological studies alone;¹⁸ however, that percentage decreases when the information provided by neuropsychological testing is concordant with other studies. A major problem in LMD is that there is a high error rate due to language dominance, as discussed above; that is, verbal memory deficit does not always indicate dysfunction of the left cerebral hemisphere.

Table 108-1 Most Frequently Used Tests in Epilepsy

General BatteriesWechsler Intelligence ScaleHasltead-Reitan BatteryHemispheric lateralizationWada TestDichotic ListeningFunctional Magnetic Resonance ImagingAttentionTrail Making TestCancelation TestLanguageBoston Diagnostic Aphasia ExaminationBoston Naming TestToken TestVisuospatial and PerceptualHooper Visual Organization TestConstructional ApraxiaBenton Judgement of Line OrientationMotor and Reaction TimeFinger OscillationHand DynamometerGrooved Pegboard

Problem Solving, FlexibilityWisconsin Card Sorting TestWord FluencyStroop TestBattery of Learning and MemoryWechsler Memory ScaleVerbal Learning and MemoryStory RecallPaired Word LearningRey Auditory Verbal Learning TestCalifornia Verbal Learning TestVisuospatial Learning and MemorySimple Designs RecallRey Osterrieth Complex FigureBenton Visual Retention TestOthersBeck Depression InventoryQuality of Life in Epilepsia (QOLIE-31)International Neuropsyquiatric Interview (MINI)

Imaging Studies

The best imaging method to study intractable epilepsy is magnetic resonance imaging (MRI) because of its excellent spatial resolution employing basic sequences such as T1WI, T2WI, and FLAIR. It has high sensitivity for characterizing signal intensity of normal and pathologic brain tissue and very good specificity for neoplastic, vascular, atrophic, dysplastic, infectious, and degenerative etiologies. MRI allows the differentiation of edema, demyelinating diseases, heterotopic gray matter (Fig. 108-3), and space-occupying lesions involving anatomic structures causing epilepsy.

FIGURE 108-3 A and B, Axial and coronal images, showing migration and sulcation disorders, with gray matter nodular heterotopy. Note the abnormal localization of gray matter in deep white matter lateral to right ventricle with ependymal extension (arrows).

In a series of 40 patients with refractory focal epilepsy, Knake et al.³⁸ found that studies with 3T phased-array surface coil (PA-MRI) yielded additional diagnostic information in 48% of the studies (19/40), when compared to routine clinical MRI performed at 1.5T. In the subgroup of patients with previous 1.5T MRIs interpreted as normal, 3T PA-MRI resulted in the detection of a new lesion in 65% of patients (15/23). In the subgroup of 15 patients with known lesions, 3T PA-MRI better defined the lesion in 33% (5/15). On the other hand, Zijlmans et al.³⁹ stated that patients studied with 1.5T show loss of cerebral tissue and mesial temporal sclerosis better than at 3T, while those patients with cerebral dysplasias are better studied with 3T. High-resolution 3T MRI (HR 3T MRI) and surface coils applied over the suspected epileptogenic zone are useful to detect lesions in patients suffering refractory epilepsy due to cortical developmental malformations (CDM).⁴⁰

In order to optimize the diagnosis of mesial temporal sclerosis and the severity of hippocampal atrophy, it is important to obtain a precise hippocampal evaluation with axial and coronal images in MRI. Axial images oriented perpendicular to the axis of the clivus, 2-mm thick without any gaps, provide an adequate view of the hippocampal structures. Coronal images are taken perpendicular to axial sections. Hippocampal areas can be evaluated with these regions of interest (ROI) measurement to define possible differences in volumetric areas indicating hippocampal atrophy (Fig. 108-4A). Flair sequences offer an objective method to evaluate hippocampal area signal intensity in order to define hippocampal atrophy and mesial temporal sclerosis (Fig. 108-4B) that may be associated to ipsilateral mammillary body and fornix atrophy (Fig. 108-5). Successful surgery is possible even with normal MRI but it requires compelling clinical and electrophysiologic evidence of seizure onset.

FIGURE 108-4 A, T2 coronal image with region of interest measurement of the hippocampus. There is atrophy and hyperintensity on the left due to hippocampal sclerosis (arrow). B, Flair sequence of coronal image showing left hippocampal hyperintensity (arrow), corresponding to sclerosis and atrophy.

FIGURE 108-5 T1 coronal images. Left hippocampal sclerosis is associated with widening of temporal horn and ipsilateral atrophy of fornix (A) and mammillary body (B) (arrows).

Magnetic Resonance Spectroscopy

While MRI is primarily employed to obtain structural images of the brain, magnetic resonance spectroscopy (MRS) can assess regional cell loss through determination of the concentrations of intermediate metabolites, including glutamate and glutamine.⁴¹ This noninvasive technique can also measure other metabolites of cellular activity such as N-acetyl-aspartate (NAA), creatine (Cr), and choline (Ch) that give indirect information regarding cellularity of the ROI. MRS provides also a broad range of useful functional information such as cerebral concentrations of GABA and glutamate, usually associated with an increase in pH and inorganic phosphate and reduction of phosphate monoesters. Several studies in patients with epilepsy have documented neuronal loss and alterations in energy and lipid metabolism, acid–base homeostasis, and amino acid neurotransmitter metabolism.⁴² Proton MRS imaging studies consistently demonstrate decreased NAA in the epileptogenic temporal lobe (Fig. 108-6).

FIGURE 108-6 Hippocampal univoxel spectroscopy. There is bilateral reduction of N-acetyl-aspartate compatible with hippocampal sclerosis.

Functional magnetic resonance imaging (fMRI) is a noninvasive functional brain mapping technique assessed on blood oxygen level–dependent (BOLD) signal with echo planar images (EPI) obtained during T1-weighted imaging MRI studies. It offers a map of physiologic and metabolic functions of cerebral activity during ictal and interictal discharges on images with a spatial resolution of a few millimeters and a temporal resolution of a few seconds.^43,⁴⁴ One of the first clinical applications of fMR was presurgical evaluation of cerebral function in patients with epilepsy and neoplastic lesions nearby eloquent areas. This technique detects the localization of the functional areas of primary sensorimotor cortex or language zones prior to surgery. fMRI offers noninvasive preoperative brain mapping with high sensitivity to detect cerebral lesions and defining the border between lesion and normal functional cortex. It may also predict possible deficits in motor, sensory, or language functions due to expansion of the lesion or surgical procedures. Therefore, it offers information to help therapeutic decisions relative to risk–benefit ratio of the treatment. In patients with refractory epilepsy fMR has been used to evaluate the resection feasibility, planning the surgical procedure and better patient selection for invasive mapping⁴⁵ (Fig. 108-7). Functional MRI holds great promise as a powerful tool in memory evaluation.³¹ fMRI aids in the localization of language and motor function of candidates for epilepsy surgery, and has up to a 90% concordance with WADA test (Fig. 108-1).⁴⁶