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.     

Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood

A 21-year-old male presented with temporal lobe epilepsy associated with a venous angioma in the ipsilateral frontal lobe, presenting as intractable complex partial seizures. Neuroimaging showed a cerebral venous angioma in the right dorsolateral and opercular frontal lobe, and atrophy of the right hippocampus. As the ictal electroencephalogram (EEG) obtained with subdural electrodes indicated spike discharges initiating from the right mesial temporal lobe, temporal lobectomy was performed. The patient was seizure-free after the operation. Patients with epilepsy who have a cerebral venous angioma require precise analysis of the seizure pattern and an ictal EEG because of cerebral venous angioma may be associated with an another epileptogenic lesion which is surgically treatable.     

Scalp-recorded, ictal focal DC shift in a patient with tonic seizure

PURPOSE: We recorded focal ictal DC shifts from scalp electrodes in a 9-year-old boy with intractable, clinically generalized tonic seizures. The patient had a high intensity signal abnormality of the left temporal cortex with thickening of the gyri on T2-weighted MRI. METHODS: Scalp digital EEGs were recorded using electrodes made of silver/silver chloride. The low frequency filter (LFF) was set at 0.016 Hz. Recorded seizures were subsequently analyzed with LFF settings of 1.0, 0.016 and 0.03 Hz. RESULTS: All recorded seizures initially showed diffuse, low voltage, high frequency activity (electrodecremental pattern) followed 10-20 s later by quasirhythmic activity over the left frontotemporal region. In two seizures, LFF of 0.016-0.03 Hz revealed a slow negative shift over the left frontotemporal area simultaneously with onset of the bilateral electrodecremental pattern. However, in the other seizures, this initial slow negative shift was obscured by artifacts. Subsequent electrocorticography (ECoG) delineated frequent epileptiform discharges in the left temporal as well as frontal cortex. CONCLUSIONS: Scalp-recorded ictal DC shifts may help identify focal epileptogenic brain area in patients with clinically generalized seizures although the technique is vulnerable to artifact.     

In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging may be useful in presurgical evaluation of refractory complex partial seizures.     

Preoperative EEG in medically intractable epilepsy

The aim of the preoperative neurophysiological investigations is to identify the primary epileptogenic focus and its relation to functional cortical areas. The investigations include interictal and ictal extracranial (scalp) electroencephalography (EEG) and invasive methods (depth, subdural, foramen ovale electrodes and peroperative electrocorticography). If an epileptic focus is located in the anterior part of the temporal lobe by the use of scalp EEG, this is normally regarded as sufficient for an anterior lobectomy. However, because of poor spatial resolution by scalp EEG, it is difficult to separate mesial from lateral foci, identify the exact extent of posterior temporal or extra-temporal foci, identify the primary focus in patients with bilateral abnormalities and identify cases with minor scalp EEG-changes. As invasive EEG shows higher spatial resolution and gives an opportunity to evaluate functional areas, invasive EEG has significant advantages in these patients. Use of invasive EEG bears a slightly increased risk and discomfort to the patient, but is necessary in the presurgical evaluation of some patients suffering from medically intractable epilepsy.     

A case of intractable temporal lobe epilepsy: discrepancy between epileptogenic area and structural lesion demonstrated by subdural recording

We reported a 25-year-old man with intractable right temporal lobe epilepsy in whom subdural recording successfully delineated the epileptogenic area in the right anterior mesial to basal temporal region in spite of the presence of a postoperative lesion in the right posterior temporal region. The patient underwent right posterior temporal resection due to ependymoma at the age of 8 years. Since age 19, he had suffered from medically intractable psychomotor seizures. Ictal scalp-recorded EEG suggested an epileptogenic area at the right temporal area, but it could not specifically demarcate the site because of bone deficits from the previous surgery. Ictal SPECT showed a hyperactive area in the right anterior temporal area, which was inconsistent with the MRI finding. In case of partial epilepsy associated with structural lesion like in the present case, if results of various non-invasive studies are discrepant as to the epileptogenic area, invasive studies using, for example, subdural EEG monitoring is necessary to determine the responsible area.     

Association of circulating endothelium and noradrenaline with increased calcium-channel binding sites in the placental bed in pre-eclampsia

PURPOSE: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short-acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike-provoking properties of clonidine in comparison to methohexital. METHODS: After oral premedication with clonidine, short-lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings. RESULTS: Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations. CONCLUSIONS: This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Single photon emission computed tomography-EEG relations in temporal lobe epilepsy

The role of single photon emission computed tomography (SPECT) as an independent confirmation test in presurgical evaluation of medically intractable temporal lobe epilepsy has not been critically investigated. Because spreading ictal discharges may cause a concomitant increase of cerebral blood flow in remote cerebral regions, a careful analysis of peri-injection EEG patterns and their relation to ictal SPECT may be important in evaluating the reliability of ictal SPECT. Both interictal and ictal EEG and SPECT were reviewed in 19 patients with temporal lobe epilepsy who achieved a successful seizure outcome after surgery. Patients were divided into unitemporal and bitemporal groups according to the lateralization of interictal epileptiform discharges (IED). Ictal EEG features were classified into lateralized and nonlateralized groups. The concordance between SPECT and EEG lateralizations was examined in each patient and correlated to the documented epileptogenic temporal lobe. Interictal SPECT correctly lateralized in eight of nine patients with unitemporal IED and in five of 10 patients with bitemporal IED. Ictal SPECT was highly concordant with the peri-injection ictal EEG but correctly lateralized the epileptogenic region in only 11 of 19 patients. When both pre- and postinjection EEG epochs lateralized ipsilaterally, all ictal SPECT images showed concordant lateralization. If pre- and postinjection EEG epochs were either different in lateralization or nonlateralization, ictal SPECT images often showed complex patterns of cerebral perfusion with a high incidence of false lateralization. Interictal SPECT was more sensitive and reliable in patients with unitemporal IED than in patients with bitemporal IEDs. Ictal SPECT was closely related with peri-injection EEG epochs but with frequent false lateralization. The role of ictal SPECT as an independent confirmation test in presurgical evaluation should be reappraised.     

Continuous source imaging of scalp ictal rhythms in temporal lobe epilepsy

PURPOSE: We wished to determine whether continuous EEG source imaging can predict the location of seizure onset with sublobar accuracy in temporal lobe epilepsy (TLE). METHODS: We retrospectively analyzed the earliest scalp ictal rhythms, recorded with 23- to 27-channel EEG, in 40 patients with intractable TLE. A continuous source analysis technique with multiple fixed dipoles (Focus 1.1) decomposed the EEG into source components representing the activity of major cortical sublobar surfaces. For the temporal lobe, these were basal, anterior tip, anterolateral, and posterolateral cortex. Ictal EEG onset was categorized according to its most prominent and leading source component. All patients underwent intracranial EEG studies before epilepsy surgery, and all had a successful surgical outcome (follow-up >1 year). RESULTS: Most patients with ictal rhythms having a predominant basal source component had hippocampal-onset seizures, whereas those with seizures with prominent lateral source activity had predominantly temporal neocortical seizure origins. Seizures with a prominent anterior temporal tip source component mostly had onset in entorhinal cortex. Seizures in some patients had several equally large and nearly synchronous source components. These seizures, which could be modeled equally well by a single oblique dipole, had onset predominantly in either entorhinal or lateral temporal cortex. CONCLUSIONS: Multiple fixed dipole analysis of scalp EEG can provide information about the origin of temporal lobe seizures that is useful in presurgical planning. In particular, it can reliably distinguish seizures of mesial temporal origin from those of lateral temporal origin.     

Significance of interictal temporal lobe delta activity for localization of the primary epileptogenic region

Because interictal temporal lobe delta activity (TLDA) has been described in 30 to 90% of patients with temporal lobe epilepsy (TLE) but has not been investigated in patients with extratemporal epilepsy, we sought to determine the localizing significance of TLDA. We compared the presurgical interictal scalp EEG results of 47 consecutive patients who received extratemporal resection (40 frontal and 7 parietal-occipital) for intractable epilepsy with 43 consecutive patients who received anterior temporal lobectomy. We defined lateralized TLDA as runs of lower than 4-Hz waveforms that were easily distinguished from the background rhythms and were maximal at electrodes T4, F8, and T6 or T3, F7, and T5. The lateralized TLDA was subcategorized as temporal intermittent rhythmic delta activity (TIRDA) or temporal intermittent polymorphic delta activity (TIPDA). A chi-square test was used to determine the association of the lobe of the epileptogenic zone with TIRDA and TIPDA. We found TIRDA in 12 (28%) and TIPDA in 8 (19%) patients in the temporal lobe group, and TIRDA in 2 (4%) and TIPDA in 9 (19%) patients in the extratemporal group. TIRDA was strongly associated with TLE (p < 0.003), whereas TIPDA occurred at an equal rate in both groups. Similar to anterior temporal epilepsy, lateralized TIPDA is present in up to 20% of patients with extratemporal epilepsy. The presence of TIRDA strongly suggests TLE but may infrequently occur in extratemporal epilepsy. Caution should be used when using lateralized TLDA as a presurgical localizing finding.     

Medial temporal lobe epilepsy: videotape analysis of objective clinical seizure characteristics

PURPOSE: The syndrome of temporal lobe epilepsy has been described in great detail. Here we focus specifically on the clinical manifestations of seizures originating in the hippocampus and surrounding mesial temporal structures. METHODS: Seizure origin was confirmed in 67 cases by depth EEG recording and surgical cure after mesial temporal resection. RESULTS: Among nonlateralized manifestations, we commonly found oral automatisms, pupillary dilatation, impaired consciousness, and generalized rigidity. Appendicular automatisms were often ipsilateral to the seizure focus, whereas dystonia and postictal hemiparesis were usually contralateral. Head deviation, when it occurred early in the seizure, was an ipsilateral finding, but was contralateral to the seizure focus when it occurred late. Clear ictal speech and quick recovery were found when seizures originated in the non-language-dominant hemisphere, but postictal aphasia and prolonged recovery time were characteristic of seizure origin in the language-dominant hemisphere. CONCLUSIONS: These signs help to define the mesial temporal lobe epilepsy (MTLE) syndrome and often provide information as to the side of seizure origin.     

Dipole source localization of ictal epileptiform activity

Dipole source localization of ictal epileptiform activity recorded by scalp EEG was performed in patients prior to surgical treatment. The dipole tracing method combined with the scalp-skull-brain head model was used to locate epileptogenic foci. A digital EEG system was used for data collection. The accuracy of dipole source localization was evaluated by comparing the focus location with that obtained by chronic subdural electrocorticography. In a case of frontal lobe epilepsy with epileptogenic focus in the frontoparietal convexity, the results of dipole source localization agreed well with those obtained with chronic subdural electrocorticography. In a case of lateral temporal lobe epilepsy, the results of dipole source localization were consistent with those obtained with chronic subdural electrocorticography, but a small localization error was observed. The clinical usefulness of and suggestions for improving this method are discussed.     

Spectral EEG during short-term discontinuation of antiepileptic medication in partial epilepsy

The effect of short-term discontinuation of antiepileptic drugs (AEDs) on spectral analysis of EEG background activity (spectral EEG) was studied in patients undergoing preoperative evaluation for epilepsy surgery. We also wished to clarify whether AED discontinuation would provide lateralizing evidence in spectral EEGs of patients with temporal lobe epilepsy (TLE). Spectral EEGs were performed in 15 patients receiving their regular medication regimen and again after a 1-week period during AED withdrawal. A subgroup of 9 patients who had previously undergone temporal lobectomies (TLE group) was studied separately. In this group, we evaluated the effect of preceding seizures on spectral EEG derived from temporal neocortical areas. In all patients, spectral EEG changes were detected even after a short-term AED withdrawal. The total amount of absolute delta activity was reduced and occipital peak frequency and relative alpha activity were increased as compared with baseline values. In TLE patients with habitual seizures occurring < 20 h before the spectral EEG recording, lateralization was correctly identified by the greater amount of absolute delta activity ipsilateral to the epileptogenic focus. Epileptic seizures are accompanied by subtle focal slowing in spectral EEG for a much longer period than has been assumed. In addition, postictal spectral EEG over the temporal lobes may have lateralizing value. Further studies in larger numbers of patients are needed to evaluate the role of spectral EEG in the preoperative evaluation of patients for temporal lobe surgery.     

Functional MRI lateralization of memory in temporal lobe epilepsy

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.     

A decade of rare donor services in the United States. Report of the American Red Cross Rare Donor Registry (1981-1990)

As a substitute for depth electrodes, mesial temporal subdural electrodes were devised. This electrode has a slender trapezoid shape and is easily introduced to the inner uppermost portion of the parahippocampal gyrus. Our results have shown that mesial temporal electrodes can detect not only interictal spikes but also subclinical and clinical seizure discharges from the mesiolimbic structures, and they have excellent capability for lateralization of the mesial temporal epileptic focus. If mesial temporal subdural strips are used in combination with lateral temporal subdural grids, comprehensive understanding of the focus distribution throughout the temporal lobes will be possible without using depth electrodes.     

Lateralization of human temporal lobe epilepsy by 31P NMR spectroscopic imaging at 4.1 T

OBJECTIVE: To compare the phosphorous metabolite ratios in the mesial temporal lobe of healthy volunteers (n = 20) with the corresponding ratios in patients with temporal lobe epilepsy (n = 30) using 31P NMR spectroscopic imaging and to lateralize the seizure focus in temporal lobe epilepsy patients using various phosphorous metabolite ratios-phosphocreatine to inorganic phosphate (PCr/Pi), PCr to adenosine triphosphate (PCr/gamma-ATP), and (gamma-ATP/Pi)--and to compare with clinical lateralization results. METHODS: All 31P NMR spectroscopic imaging studies were performed on a high-field, 4.1 T, whole-body NMR spectroscopic imaging system using a 31P/1H double-tuned volume coil. RESULTS: We found an average reduction of 15% in the PCr/Pi and gamma-ATP/Pi ratios compared with the corresponding ratios in healthy volunteers in the entire mesial temporal lobe, and more than a 30% reduction in these two ratios in the anterior region of the epileptogenic mesial temporal lobe. These ratios were also reduced significantly in the ipsilateral lobe when compared with their corresponding values in the contralateral lobe. In patients we lateralized the seizure focus, based on these 31P NMR data, and compared the results with the clinical lateralization. The lateralization based on either the PCr/Pi or the gamma-ATP/Pi ratio yielded a correspondence of 70 to 73% with the final clinical lateralization. In the subgroup of patients (n = 9) that needed intracranial EEG for the presurgical lateralization because of inconclusive results from the noninvasive methods, a 78% correspondence was found with the 31P NMR-based lateralization, whereas MRI provided a correspondence of only 33%, and scalp EEG provided a correspondence of only 56%. CONCLUSIONS: These results suggest the utility of adding the 31P NMR method to the group of noninvasive modalities used for presurgical decision making in temporal lobe epilepsy patients.     

EEG findings in frontal lobe epilepsies

As a group, epilepsies of frontal lobe origin are thought to be poorly localized using surface EEG recordings. This finding may depend on the specific areas of frontal lobe from which the seizures originate or the pathologic substrate. We reviewed the presurgical surface EEGs of patients with frontal lobe epilepsy who underwent epilepsy surgery. The specific area of the frontal lobe where seizures originated was determined by 1) intracranial ictal EEG recordings, or 2) the presence of a structural lesion, identified by imaging studies in patients who achieved complete seizure control following surgery. We differentiated patients whose seizures began in the dorsolateral frontal convexity from those whose seizures began in the medial frontal region, and we correlated EEG findings in the interictal, postictal, and ictal states with seizure semiology, pathologic substrate, and surgical outcome. Four of nine patients had seizures originating in the dorsolateral frontal convexity and five had medial frontal onset seizures. Patients whose seizures originated from the dorsolateral convexity had focal interictal epileptiform abnormalities that localized to the region of seizure onset. Patients whose seizures began in the medial frontal region had either no interictal epileptiform abnormality or had multifocal epileptiform discharges. Patients whose seizures began in the dorsolateral convexity showed focal electrographic seizure activity that was localizing. This rhythmic fast activity did not appear to be substrate-specific. Patients whose seizure onset localized to the medial frontal region did not show focal electrographic seizure at clinical onset. We conclude that the scalp EEG recordings of frontal lobe epilepsies contain features that enable differentiation of seizures originating from two different regions of the frontal lobe.     

Epileptiform electroencephalographic patterns

Electroencephalography (EEG) is the most useful test for assessment of patients with epilepsy. It can help establish the diagnosis of epilepsy and determine the type of seizure disorder and its site of origin. Epileptiform abnormalities in the EEG tracing may be focal or generalized. The main types of focal epileptiform discharges arise from the temporal, frontal, occipital, centroparietal, centrotemporal, and midline regions of the brain. Generalized epileptiform discharges consist of the 3-Hz spike-and-wave, slow spike-and-wave, atypical spike-and-wave, paroxysmal fast activity, and hypsarrhythmic patterns. Status epilepticus is manifested by continuous epileptiform discharges or recurrent seizure activity without interim recovery, which can occur in a generalized or focal manner. Benign epileptiform variants unassociated with seizures can also be present in the EEG. Included in this category are the "14 & 6" positive bursts, small sharp spikes, wicket waves, 6-Hz spike-and-wave discharges, and rhythmic temporal theta activity. The EEG findings should be interpreted in the context of the overall clinical picture.     

Long-term subdural strip electrocorticographic monitoring of ictal déjà vu

We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right-handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left-handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experimental phenomenon appears to lateralize to the hemisphere nondominant for handedness.