Neocortical Epilepsy Research Articles

Is epileptogenic cortex truly hypometabolic on interictal positron emission tomography?

Positron emission tomography (PET) of glucose metabolism is often applied for the localization of epileptogenic brain regions, but hypometabolic areas are often larger than or can miss epileptogenic cortex in nonlesional neocortical epilepsy. The present study is a three-dimensional brain surface analysis designed to demonstrate the functional relation between glucose PET abnormalities and epileptogenic cortical regions. Twelve young patients (mean age, 10.8 years) with intractable epilepsy of neocortical origin underwent chronic intracranial electroencephalographic monitoring. The exact location of the subdural electrodes was determined on high-resolution three-dimensional reconstructed magnetic resonance imaging scan volumes. The electrodes were classified according to their locations over cortical areas, which were defined as hypometabolic, normometabolic, or at the border between hypometabolic and normal cortex (metabolic "border zones") based on interictal glucose PET. Electrodes with seizure onset were located over metabolic border zones significantly more frequently than over hypometabolic or normometabolic regions. Seizure spread electrodes also more frequently overlay metabolic border zones than hypometabolic regions. These findings suggest that cortical areas with hypometabolism should be interpreted as regions mostly not involved in seizure activity, although epileptic activity commonly occurs in the surrounding cortex. This feature of hypometabolic cortex is remarkably similar to that of structural brain lesions surrounded by epileptogenic cortex. Cortical areas bordering hypometabolic regions can be highly epileptogenic and should be carefully assessed in presurgical evaluations.

The role of the intracarotid amobarbital procedure in evaluation of patients for epilepsy surgery.

To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization-related epilepsy. We retrospectively studied 111 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance. Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All 11 mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection. In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by noninvasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.

Intracranial EEG seizure-onset patterns in neocortical epilepsy.

We investigated neocortical seizure-onset patterns recorded by intracranial EEG with regard to anatomic location, pathologic substrate, and prognostic value for surgical outcome. Seizure onset was analyzed in 53 neocortical resective epilepsy surgery patients. Anatomic location was divided into temporal and extratemporal. Pathologic substrate was classified as developmental, mature, and negative or non-specific gliosis. Onset frequency was categorized by visual analysis into tradition EEG frequency bands. Spatial extent was divided into focal (fewer than four contacts) and regional (more than five contacts). Waveform at seizure onset was divided into several types based on their morphology. Onset features were examined with respect to anatomic location, pathologic substrate, and surgical outcome. Seizure-onset frequency was significantly related to spatial distribution and to anatomic location. Extratemporal and regional onset were more commonly in the gamma range, and temporal and focal onset in the beta frequency range or slower. Waveform could be categorized into five different patterns, of which low voltage fast activity (LVFA) was the most common form (57%). LVFA and rhythmic alpha-theta spike activity were more common in developmental than in mature pathology, whereas rhythmic sinusoidal waves at onset were found in only mature substrates. Waveform pattern showed a possible correlation with surgical outcome (p = 0.097): LVFA and rhythmic sinusoidal waves onset patterns were associated with favorable outcome more often (40.4%) than the other three patterns (6.3%). Slow onset suggested poor outcome in the subgroup of developmental pathology (p = 0.062). Certain electrographic seizure-onset features are associated with specific substrates and outcomes, whereas others reflect the anatomic location and its connections independent of the pathology.

Neocortical temporal lobe epilepsy: intracranial EEG features and surgical outcome.

Patients with neocortical temporal lobe epilepsy (NTLE) may have less favorable outcome with anterior temporal lobectomy than those with mesial temporal foci. The authors analyzed ictal intracranial electroencephalograms (EEGs) in patients with NTLE to identify features that predict surgical outcome. The following intracranial ictal EEG features in 31 consecutive medically intractable NTLE patients were studied: Frequency (i.e., low-voltage fast [>20 Hz], recruiting ictal-onset spikes, ictal-onset rhythms less than 5 Hz, ictal-onset rhythms with repetitive sharp waves between 5 and 20 Hz); extent of ictal onset (focal, sublobar, and lobar); localization within the temporal lobe (anterior, posterior, or regional); and the time to seizure spread outside the temporal lobe (rapid, intermediate, and slow). The average follow-up period was 36.7 months (range, 18 to 60 months). Findings between two outcome groups were compared: class I group (seizure-free) and class II to IV group (persistent seizures). Twenty-one (66.7%) of 31 patients with NTLE were seizure-free. Intracranial EEG features which were significantly associated with seizure-free outcome were focal or sublobar onset, anterior temporal onset, and slow propagation time (P < 0.05). There was a trend for patients with ictal onset morphologies of slow ictal-onset rhythm and repetitive sharp waves to be seizure-free (P = 0.07). Intracranial EEG is helpful in predicting surgical outcome in NTLE patients.

Intracranial EEG in temporal lobe epilepsy.

Intracranial EEG monitoring before epilepsy surgery, while becoming less commonly performed in patients with unilateral mesial temporal lobe epilepsy, is still widely used when bilateral independent temporal lobe seizures are suspected or when extratemporal foci cannot be ruled out by noninvasive means. Additionally, many epilepsy centers are reporting excellent surgical outcome in patients with neocortical temporal lobe epilepsy, when resections are guided by intracranial EEG studies. This article reviews the indications, technical aspects, risks, and interpretation of intracranial EEG in patients with temporal lobe seizures. It also considers intracranial EEG features predictive of surgical outcome.

Association of ipsilateral motor automatisms and contralateral dystonic posturing: a clinical feature differentiating medial from neocortical temporal lobe epilepsy.

Clinical features that may help to differentiate medial temporal lobe epilepsy (MTLE) from neocortical temporal lobe epilepsy (NTLE) are lacking. To investigate the localizing and lateralizing value of the association of ipsilateral motor automatisms and contralateral dystonic posturing in patients with medically refractory temporal lobe epilepsy. Videotapes of 60 patients with well-defined MTLE, NTLE, or both were reviewed to assess the presence and the localizing value of unilateral dystonic posturing associated with motor automatisms. Twenty-eight of the 60 patients exhibited unilateral dystonic posturing. This sign was observed in patients with MTLE and NTLE. It was mostly contralateral to the seizure focus in patients with MTLE and exclusively ipsilateral in patients with NTLE. Unilateral motor automatisms occurred in 26 of the 60 patients with MTLE or NTLE. It was predominantly ipsilateral to the seizure focus in patients with MTLE and exclusively contralateral in patients with NTLE. The association of ipsilateral motor automatisms and contralateral dystonic posturing was found in 14 patients with MTLE but in none of the patients with NTLE. Two patients who had medial and neocortical seizure onset also exhibited this clinical feature. This association was not significantly correlated with the postoperative outcome in patients with MTLE. The association of ipsilateral motor automatisms and contralateral dystonic posturing may help to differentiate MTLE from NTLE with a reliable lateralizing value. This clinical association may reflect a specific pattern in the spread of the ictal discharge.

Ictal patterns of neocortical seizures monitored with intracranial electrodes: correlation with surgical outcome.

Numerous factors have been analyzed in attempts to predict the outcome of surgical resections in patients with neocortical epilepsy. We examined the correlation between surgical outcome and electrocorticographic features of neocortical ictal patterns. Twenty six patients with neocortical epilepsy underwent monitoring with subdural grid electrodes before surgery. Ictal patterns were analyzed retrospectively and correlated with three types of outcome: seizure free, worthwhile improvement (>75% reduction of seizure frequency), and no worthwhile improvement. The duration of follow-up was 2-5 years. Ictal patterns were divided according to the size of epileptogenic zone (focal, regional, multifocal); velocity and type of seizure propagation (fast contiguous, slow contiguous, noncontiguous); pattern of the onset of ictal activity; part of the cortex involved in the origin of the seizure (frontal, frontocentroparietal, etc.). Spread to medial temporal structures (as assessed by subtemporal strips) also was evaluated in selected cases. Statistically significant correlation with surgical outcome (p = 0.026) was shown for only one variable: type of spread. Patients with slow spread (n = 8) demonstrated the best outcomes (five are seizure free), whereas patients with noncontiguous spread (n = 5) demonstrated the worst outcomes (four did not improve significantly). Patients with fast contiguous spread (n = 13) showed intermediate outcomes. Types of propagation of ictal neocortical activity correlate with surgical outcome. Analysis of ictal pattern during intracranial recordings may help to predict surgical outcome for neocortical epilepsy.

Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype.

The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Ten MR studies were read prospectively as showing FCD; these case histories, electroencephalographic studies, and neuroimaging data were reviewed. Eight of these patients subsequently underwent focal cortical resection guided by intraoperative electrocorticography. The MR findings were correlated with pathological findings in these 8 patients. For purposes of radiological-pathological correlation, the FCD lesions were divided into two classes. Radiological classification was based on the absence (type A) or presence (type B) of T2 prolongation of the subcortical white matter. Pathological grading as type I or type II was based on a previously described pathological grading system. Specific MR findings associated with FCD included focal blurring of the gray-white matter interface (n = 9), thickening of the cortical ribbon (n = 7), and T2 prolongation of the subcortical white matter (n = 4). In 3 patients, the only MR finding that suggested FCD was localized blurring of the gray-white matter junction. In 2 of these 3 patients, the MR diagnosis of FCD could be made only by FMPIR. FCD was confirmed histologically in 7 of 8 patients, with insufficient tissue for complete histopathological evaluation in 1 case. Radiological classification of FCD agreed with pathological classification in 5 of 7 cases. Correlation of MR findings with intraoperative electrocorticography results indicated that the MR study localized the epileptogenic lesion correctly in 8 of 8 cases. Scalp ictal electroencephalographic studies localized the epileptogenic lesion in 5 of 8 cases; positron emission tomographic scans were focally abnormal in 3 of 3 cases. FMPIR MR imaging permitted accurate diagnosis and localization of FCD in all patients with pathologically proved FCD. MR identification of FCD aided presurgical planning and intraoperative management of these patients.

Magnetoencephalography in partial epilepsy: Clinical yield and localization accuracy

The goals of this study were to determine (1) the yield of magnetoencephalography (MEG) according to epilepsy type, (2) if MEG spike sources colocalize with focal epileptogenic pathology, and (3) if MEG can identify the epileptogenic zone when scalp ictal electroencephalogram (EEG) or magnetic resonance imaging (MRI) fail to localize it. Twenty-two patients with mesial temporal (10 patients), neocortical temporal (3 patients), and extratemporal lobe epilepsy (9 patients) were studied. A 37-channel biomagnetometer was used for simultaneously recording MEG with EEG. During the typical 2-3-hour MEG recording session, interictal epileptiform activity was observed in 16 of 22 patients. MEG localization yield was greater in patients with neocortical epilepsy (92%) than in those with mesial temporal lobe epilepsy (50%). In 5 of 6 patients with focal epileptogenic pathology, MEG spike sources were colocalized with the lesions. In 11 of 12 patients with nonlocalizing (ambiguous abnormalities or normal) MRI, MEG spike sources were localized in the region of the epileptogenic zone as ultimately defined by all clinical and EEG information (including intracranial EEG). In conclusion, MEG can reliably localize sources of spike discharges in patients with temporal and extratemporal lobe epilepsy. MEG sometimes provides noninvasive localization data that are not otherwise available with MRI or conventional scalp ictal EEG.

Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy.

To determine whether lesional neocortical temporal lobe epilepsy (NTLE) can be differentiated from mesial temporal lobe epilepsy (MTLE) during the noninvasive presurgical evaluation, we compared the historical features, seizure symptomatology, and surface EEG of 8 patients seizure free after neocortical temporal resection with preservation of mesial structures and 20 patients after anterior temporal lobectomy for MTLE. Seizure symptomatology of 107 seizures (28 NTLE, 79 MTLE) was analyzed. One hundred one ictal EEGs (19 NTLE, 82 MTLE) were reviewed for activity at seizure onset; presence, distribution, and frequency of lateralized rhythmic activity (LRA); and distribution of postictal slowing. Seizure symptomatology and EEG data were compared between groups, and sensitivity, specificity, and positive and negative predictive values were determined for variables that differed significantly. Multiple logistic regression was used to determine whether patients could be correctly classified as having MTLE or NTLE. MTLE patients were younger at onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications, or head injury. NTLE seizures lacked features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation, and postictal cough or sigh. NTLE ictal EEG recordings demonstrated lower mean frequency of LRA that frequently had a hemispheric distribution, whereas LRA in MTLE seizures was maximal over the ipsilateral temporal region. We conclude that it may be possible to differentiate lesional NTLE from MTLE on the basis of historical features, seizure symptomatology, and ictal surface EEG recordings. This may assist in the identification of patients with medically refractory nonlesional NTLE who frequently require intracranial monitoring and more extensive or tailored resections.

Clinical applications of magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) is a new tool for evaluation of patients with epilepsy, demonstrating abnormalities of energy and lipid metabolism ictally and, more recently, interictally. These metabolic abnormalities include increased inorganic phosphate, pH, and decreased phosphomonoesters as determined by 31P MRS, as well as decreased N-acetylaspartate determined by 1H MRS. Furthermore, increased lactic acid has been detected postictally. These metabolic changes appear to be confined to the region of seizure origination and can be detected interictally. Therefore, they can be used for lateralization of the epileptogenic focus. Ongoing research suggests that these abnormalities may also be useful in localization of the focus, demonstrating metabolic alterations in temporal lobe epilepsy (TLE) similar to those in neocortical epilepsy. However, further technical development will be required before the goal of using these techniques for localization of the epileptogenic focus can be realized. For TLE lobe epilepsy at least, the clinical utility of 1H MRS to lateralize the seizure focus has clearly been demonstrated by several centers. The consistent findings in TLE suggest that 1H MRS is ready to become part of the evaluation process of patients with medically refractory epilepsy being evaluated for seizure surgery.

Ictal patterns in temporal lobe epilepsy recorded by epidural screw electrodes

In a consecutive series of 11 patients with a history of medically refractory temporal lobe epilepsy, we studied the appearance of ictal patterns detected by epidural screw electrodes (ESE) placed in an effort to obviate depth electrode recording. All had prior scalp-sphenoidal monitoring with aignificant obscuration of ictal EEG by movement and muscle artifact. Six to 10 ESE were placed at bilateral temporal locations of the 10% system. Ictal findings in 4–15 partial seizures from 8 patients with mesiobasal (MBTLE) and 3 patients with neocortical (NCTLE) epilepsy were correlated with imaging and histology. Five of 8 patients with MBTLE had discrete high frequency discharges at onset, evolving within 10 s to focal theta at ESE, before appearing at scalp electrodes. All had Class 1A outcome with mesial temporal sclerosis (MTS). Three of 8 patients with MBTLE and MTS had less discrete onsets, with Class 1A, 1B and 3A outcomes. Two patients with NCTLE had lesions; a grade II oligoastrocytoma with rhythmic delta at ESE and Class 4 outcome, and an anterior temporal cavernous angioma with variable onsets, some of which were high frequency, with a Class 1A outcome. The third NCTLE patient demonstrated focal theta as an ictal pattern, had no lesion and a Class 1A outcome. Ictal onsets may be well localized in selected patients by ESE. A majority of patients with MTS display well defined high frequency ictal discharges.

Experiences of epilepsy surgery in intractable seizures with past history of CNS infection.

We studied the clinical characteristics, location of epileptogenic regions, and the surgical outcomes in 18 patients with intractable epilepsy associated with previous CNS infections. All patients underwent an extensive presurgical evaluation and 11 patients had intracranial EEG monitoring. On the basis of presurgical evaluation, epileptic regions were localized to the mesial temporal (n = 12) and the neocortical (n = 6) regions. The age of the time of CNS infection was significantly younger and the latent period of non-febrile seizures after CNS infection was longer in patients with mesial temporal lobe epilepsy (MTLE). MRI showed hippocampal atrophy and hippocampal signal changes in 11 of 12 patients with MTLE. Among 6 patients with neocortical epilepsy (NE) 5 patients had normal MRI and one showed cerebral hemi-atrophy. Surgery was successful (class I & II) in all patients with MTLE, however, in the patients with neocortical epilepsy, seizure-free results were not achieved in any patients after resective surgery (6 patients) and only 2 patients achieved Class II outcomes after a second epilepsy surgery consisting of neocortical resection. Patients with MTLE after CNS infection were differentiated from the group of neocortical epilepsy by an earlier onset of CNS infection, a prolonged latent period and a higher frequency of meningitis. The characteristic pathology in this group was hippocampal sclerosis and the surgical result was excellent. Neocortical epilepsy following CNS infection usually had no focal lesion on MRI and was associated with a relatively poor surgical result. This study suggested that the surgical outcome was influenced by the type of epileptic syndromes rather than the etiology of seizures. The association of MTLE with the younger age of CNS infections and with meningitis more frequently suggested that the neocortical neurons during infancy or early childhood may be more resistant to the epileptogenesis, or that the CNS infections in patients with MTLE might be milder in severity to cause selective injuries to the hippocampal neurons during their vulnerable stage.

Intracartotid amobarbital procedure memory performance and age at first risk for seizures distinguish between lateral neocortical and mesial temporal lobe epilepsy.

To determine whether intracarotid amobarbital procedure (IAP) memory-performance asymmetries and early risk factors for epilepsy distinguish between lateral neocortical temporal lobe epilepsy (LNTLE) and mesiobasal temporal lobe epilepsy (MBTLE). We studied 10 patients with LNTLE and 22 with MBTLE. All LNTLE patients showed (a) presence of temporal neocortical lesion or lateral seizure onset by intracranial recording, and (b) absence of mesial temporal sclerosis (MTS) by histopathologic analysis. All patients with MBTLE showed (a) video-scalp EEG seizures consistent with mesial TLE, and (b) presence of unilateral MTS by histopathologic analysis. All patients had good surgical outcomes (Engel I or II). Unilateral IAP memory performance was defined as percentage of memory items presented during hemispheric anesthesia that was recognized after recovery. IAP asymmetry scores were the differences in memory performance after right and left injections. Mean memory-asymmetry scores were significantly lower in the LNTLE than in the MBTLE group. An IAP memory asymmetry of < 25% correctly classified seven of 10 patients with LNTLE, and an asymmetry of > or = 25% correctly classified 18 of 22 patients with MBTLE. Age at first risk for epilepsy was significantly younger in those with MBTLE than in those with nonlesional LNTLE. Results suggest that both IAP memory performance and age at first risk can help distinguish between MBTLE and LNTLE.

Clinical features of neocortical temporal lobe epilepsy.

Few studies have examined the clinical features of neocortical temporal lobe epilepsy (NTLE) in carefully selected patients. We reviewed records from 21 patients with NTLE, defined by intracranial electroencephalogram (EEG), who have been seizure free for 1 year or more following temporal lobectomy. The mean age of onset at the time of first seizure was 14 years (range, 1-41 years). Febrile seizures were reported in only 2 patients (9.5%). In contrast to prior mesial temporal lobe epilepsy (MTLE) studies, seizure-free intervals between the initial cerebral insult or first seizure and habitual seizures were uncommon. Possible or known risk factors for epilepsy were reported in 13 of 21 patients (62%). Fifteen (71%) patients reported auras, with experiential phenomena being the most common type. Magnetic resonance imaging was normal or nonspecific in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and heterotopic gray matter and hippocampal atrophy in 1, and cortical dysgenesis in 1. Neuropsychological testing showed deficits consistent with the seizure focus in 13 patients (62%), and Wada test showed ipsilateral memory deficits in 10 (48%). The most common behavioral manifestation was a motionless stare at ictal onset (48%). In contrast to prior studies of MTLE, only 1 NTLE patient had frequent independent, contralateral temporal lobe epileptiform spikes on scalp EEG.

Subdural Recording of Ictal DC Shifts in Neocortical Seizures in Humans

Invasive ictal EEG recording is often necessary to delineate epileptogenic areas in patients with intractable partial epilepsy, but even intracranial ictal recordings often reveal ill-defined onset zones in neocortical epilepsy. We studied the physiologic significance of ictal direct current (DC) potentials recorded intracranially in human epilepsy. We made intracranial ictal EEG recordings in three patients with intractable partial seizures arising from frontal, lateral temporal, and parietal neocortical areas by using closely spaced subdural electrodes (platinum in two patients and stainless steel in one patient) with both standard (1.5 Hz) and open (0.016 Hz) low-frequency filter (LFF) settings. The initial ictal pattern was localized to two to nine subdural electrodes and characterized by very low voltage and high-frequency rhythmic activity ("electrodecremental pattern"). A slow-rising negative potential (DC potential) was seen in a slightly more restricted area (two to six electrodes) and occurred 1-10 s before the initial ictal EEG discharges in two patients. These results agree with those of previous studies of ictal DC shifts in animals and suggest that ictal DC shifts may be helpful in delineating the epileptogenic area more precisely in human epilepsy.

Central neocortical epilepsy: Hypothesis and surgical approach

From a large series of epilepsy surgeries, we identified a spectrum of epileptogenic infarctions involving central neocortex. The severest end of this spectrum includes patients with the well-known syndrome of infantile hemiplegia. On magnetic resonance imaging (MRI), they show major hemispheric damage in the middle cerebral arterial distribution with or without involvement of other vessels. They usually have widespread EEG abnormalities and are best treated with hemispherectomy. The middle of this spectrum includes patients with infarction involving one or two branches of the middle cerebral artery (MCA) with varying degrees of hemiplegia. They can be treated with focal resection of only the infarcted tissue. The mildest form of this spectrum is represented by patients showing minimal to no MRI evidence of cerebral infarction and minimal to no neurologic deficit, but with histopathologic cortical abnormalities consistent with mild infarction. Such patients are candidates for multiple subpial transections (MST) when the epileptogenic focus involves indispensable cortex.

Critical evaluation of animal models for localization-related epilepsies.

There are many forms of human partial seizures and many human localization-related epilepsies. Idiopathic epilepsies undoubtedly have pathophysiologic substrates different from those of symptomatic epilepsies, and there is evidence that some forms of limbic epilepsy involve different epileptogenic mechanisms than neocortical epilepsies. Although these mechanisms are best studied and understood by direct investigations of patients, this is often impractical and experimental animal models are also necessary. The use of experimental animals requires that the relevance of each model to a human condition be determined. Human epilepsies are comprised of multiple component parts which can be modeled independently. For instance, acute animal models provide opportunities to study epileptic seizures, but chronic models are necessary for investigation of processes relevant to epileptic conditions, such as epileptogenesis, transition from interictal to ictal state, and long-term consequences of epilepsy. Interactions between localized epileptic activity and cerebral maturation can also be studied in the animal laboratory. Experimental animal models of human partial seizures and localization-related epilepsies can be used to further investigations on basic mechanisms that cannot be pursued in patients, and to develop hypotheses concerning the fundamental neuronal processes underlying epilepsy and epilepsy-related phenomena that subsequently can be validated in patients. In addition, it would be of great clinical utility to develop animal models of partial seizures or localization-related epilepsy that could be used cost-effectively to screen potential anti-epileptic drugs.

Symbiosis between in vivo and in vitro NMR spectroscopy: The creatine, N-acetylaspartate, glutamate, and GABA content of the epileptic human brain

High resolution 1H NMR spectroscopy was used to analyze temporal lobe biopsies obtained from patients with epilepsy. Heat-stabilized cerebrum, dialyzed cytosolic macromolecules, and perchloric acid extracts were studied using one- and two dimensional spectroscopy. Anterior temporal lobe neocortex was enriched in GABA, glutamate, alanine, N-acetylaspartate, and creatine. Subjacent white matter was enriched in aspartate, glutamine, and inositol. The N-acetylaspartate/creatine mole ratio was lower in anterior temporal neocortex with mesial (0.66) than neocortical (0.80) temporal lobe epilepsy. Human brain biopsy samples were separated into crude and refined synaptosomes, neuronal cell bodies, and glia using density gradient centrifugation. Neuronal fractions were enriched in glutamate and N-acetylaspartate. Glial cell fractions were enriched in lactate, glutamine, and inositol. The creatine content was the same in biopsied epileptic cortex (8.8–8.9 mmol/kg) and normal in vivo occipital lobe (8.9 mmol/kg). Glutamate content was higher in epileptic cortex at biopsy (10.1–10.5 mmol/kg) than normal in vivo occipital lobe (8.8 mmol/kg). GABA content was higher in biopsies of epileptic cortex (2.3–2.2 mmol/kg) than in normal in vivo occipital lobe (1.2 mmol/kg). N-acetylaspartate content was lower in biopsied epileptic temporal cortex (5.8–6.8 mmol/kg) than normal in vivo occipital lobe (8.9 mmol/kg). Paired in vivo and ex vivo measurements are critical for a firm understanding of the changes seen in the 1H-spectra from patients with epilepsy.

Comparisons of MEG, EEG, and ECoG source localization in neocortical partial epilepsy in humans

In order to delineate the characteristics of epileptic spikes, 1946 different spikes were studied in 6 patients with complex partial epilepsy. Non-invasive MEG and EEG source analyses of interictal spikes were contrasted to ECoG localization, surgical outcome and presence of lesions on MRI. Results indicated that: (1) using the most frequent occurring spike topography patterns from a large sample of spikes improved goodness-of-fit values for both MEG and EEG localization, (2) when spike patterns could be appropriately matched on several successive MEG measurements to provide an adequate matrix (3 of 6 subjects), there was excellent agreement between MEG dipole sources and ECoG sources as well as surgical outcome and presence of MRI lesions, (3) EEG sources analyse also gave good results but not as consistently as MEG.