A Stereoelectroencephalographic (SEEG) Study of Light-Induced Mesiotemporal Epileptic Seizures

Summary: Purpose: This study explored the mechanism of light-induced complex partial seizures by using ictal intracerebral recordings in a patient with refractory epilepsy of the right temporal lobe.
Methods: Presurgical evaluation of this patient was realized by means of video-EEG recordings, WADA test, magnetic resonance imaging (MRI), F¹⁸-deoxyglucose and C¹¹-flumazenil positron emission tomography (PET) interictal neuroimaging data, and stereoelectroencephalographic (SEEG) ictal recordings.
Results: SEEG investigations demonstrated the right mesiotemporal origin of all the patient's seizures. This result was confirmed by a successful right temporal lobectomy. Moreover, SEEG recordings revealed a frequent interictal spiking activity in the right occipital visual cortex that was undetectable on scalp recordings. However, the occipital cortex was not involved at the onset of mesiotemporal ictal discharges and was not hyperresponsive to focal electrical stimulation.
Conclusions: This study shows that, in spite of interictal occipital spiking, the photosensitivity of mesiotemporal seizures can be observed in both the absence of occipital cortex involvement during ictal discharges and demonstrable hyper-excitability of the occipital cortex to light or direct electrical stimulation.     

Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study

PURPOSE: In this study, we report the clinical features of insular lobe seizures based on data from video and stereo-electroencephalographic (SEEG) ictal recordings and direct electric insular stimulation of the insular cortex performed in patients referred for presurgical evaluation of temporal lobe epilepsy (TLE). METHODS: Since our first recordings of insular seizures, the insular cortex has been included as one of the targets of stereo-electroencephalographic (SEEG) electrode implantation in 50 consecutive patients with TLE whose seizures were suspected to originate from, or rapidly to propagate to, the perisylvian cortex. In six, a stereotyped sequence of ictal symptoms associated with intrainsular discharges could be identified. RESULTS: This ictal sequence occurred in full consciousness, beginning with a sensation of laryngeal constriction and paresthesiae, often unpleasant, affecting large cutaneous territories, most often at the onset of a complex partial seizure (five of the six patients). It was eventually followed by dysarthric speech and focal motor convulsive symptoms. The insular origin of these symptoms was supported by the data from functional cortical mapping of the insula by using direct cortical stimulations. CONCLUSIONS: This sequence of ictal symptoms looks reliable enough to characterize insular lobe epileptic seizures (ILESs). Observation of this clinical sequence at the onset of seizures on video-EEG recordings in TLE patients strongly suggests that the seizure-onset zone is located not in the temporal but in the insular lobe; recording directly from the insular cortex should occur before making any decision regarding epilepsy surgery.     

Acute alteration of emotional behaviour in epileptic seizures is related to transient desynchrony in emotion-regulation networks.

OBJECTIVE: During focal epileptic seizures, patients may express intense agitation, screaming and facial expressions of rage, fear or anger. The precise anatomical origin of such intense ictal emotional behaviour is not fully understood and the mechanisms by which the epileptic discharges provoke these phenomena are unknown. In the present study, we analysed the neurophysiological mechanisms underlying ictal emotional behaviour in 3 patients with frontal lobe epilepsies undergoing intracerebral recordings for presurgical evaluation. METHODS: We analyzed the interactions between regions forming 'emotional networks', before and during behavioural alterations. Intracerebral recordings (SEEG method) of seizures from 3 patients presenting with frontal lobe seizures were analyzed. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between brain structures. RESULTS: We found that these intense emotional alterations were associated with a decrease of synchrony between signals recorded from the neural networks known to be involved in emotional processing, and in particular a loss of synchrony between the orbito-frontal cortex and the amygdala. This disruption of functional connections could then result in the disruption of emotional regulation leading to the release of altered behaviour, as observed in epileptic patients during seizures. CONCLUSIONS: We propose that the occurrence of intense ictal emotional behaviour disturbance in frontal lobe seizures is related to a disruption of the normal mechanisms of emotional regulation SIGNIFICANCE: These results provide some insight into our understanding of the pathophysiological processes involved in human partial epilepsies as well as in the interpretation of clinical semiology.     

Nonconvulsive Status Epilepticus: EEG Analysis in a Large Series

Summary: We analyzed EEG characteristics comprehensively in a large series of nonconvulsive status epilepticus (NCSE) cases. Eighty-five ictal episodes in 78 patients were analyzed. The ictal discharges were generalized (group G) in 59 episodes (69%), diffuse with focal predominance (group GF) in 15 (18%), and focal (group F) in 11 (13%). The morphologies and patterns of persistence varied greatly. Frequency of ictal discharge was also variable and was almost always <3 Hz. Demonstration of focal epileptic features in response to intravenous (i.v.) diazepam (DZP) and the presence of interictal focal epileptiform discharges in some cases in groups G and GF suggested possible focal onset secondarily generalized in these cases. This study suggests that electrographically NCSE is a highly heterogeneous epileptic state, and i.v. DZP may serve as a valuable diagnostic tool in differentiating generalized from focal onset NCSE.     

Functional mapping of the insular cortex: clinical implication in temporal lobe epilepsy

PURPOSE: We report the results of 75 intracortical electrical stimulations of the insular cortex performed in 14 patients during stereo-electroencephalography (SEEG) investigation of drug-resistant partial epilepsy. The insular cortex was investigated on electroclinical arguments suggesting the possibility of a perisylvian spread or a rapid multilobar diffusion of the discharges during video EEG. METHODS: In these 14 patients, 27 stereotactically implanted transopercular electrodes reached the insular cortex (11 the right insula, 16 the left insula). Square pulses of current were applied between the two deepest adjacent contacts of each transopercular electrode using low (1 Hz) or high-frequency (50 Hz) stimulation. Only symptoms evoked in the absence of afterdischarges were analyzed. RESULTS: Clinical responses were evoked in 10 of the 14 patients (in 20 of the 27 insular sites) and showed a clear topographic specificity inside the insular cortex. Viscerosensitive and visceromotor responses, similar to those evoked by temporomesial stimulation, were evoked by anterior insular stimulation and somesthetic sensation, similar to those evoked by opercular cortex stimulation, by posterior insular stimulation. CONCLUSIONS: The topographic organization of the induced responses within the insular cortex suggest that two different cortical networks, a visceral network extending to the temporomesial structures and a somesthetic network reaching the opercular cortex, are disturbed with stimulation of the anterior or the posterior insula, respectively. Thus ictal symptoms associated with the spread of the epileptic discharges to the insular cortex might be difficult to distinguish from those usually reported during temporomesial or opercular discharges.     

Ictal headache: Headache as first ictal symptom in focal epilepsy

Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG-demonstrated ictal discharges.     

Ictal headache: headache as first ictal symptom in focal epilepsy

Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG-demonstrated ictal discharges.     

Presurgical evaluation for partial epilepsy: relative contributions of chronic depth-electrode recordings versus FDG-PET and scalp-sphenoidal ictal EEG

One hundred fifty-three patients with medically refractory partial epilepsy underwent chronic stereotactic depth-electrode EEG (SEEG) evaluations after being studied by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) and scalp-sphenoidal EEG telemetry. We carried out retrospective standardized reviews of local cerebral metabolism and scalp-sphenoidal ictal onsets to determine when SEEG recordings revealed additional useful information. FDG-PET localization was misleading in only 3 patients with temporal lobe SEEG ictal onsets for whom extratemporal or contralateral hypometabolism could be attributed to obvious nonepileptic structural defects. Two patients with predominantly temporal hypometabolism may have had frontal epileptogenic regions, but ultimate localization remains uncertain. Scalp-sphenoidal ictal onsets were misleading in 5 patients. For 37 patients with congruent focal scalp-sphenoidal ictal onsets and temporal hypometabolic zones, SEEG recordings never demonstrated extratemporal or contralateral epileptogenic regions; however, 3 of these patients had nondiagnostic SEEG evaluations. The results of subsequent subdural grid recordings indicated that at least 1 of these patients may have been denied beneficial surgery as a result of an equivocal SEEG evaluation. Weighing risks and benefits, it is concluded that anterior temporal lobectomy is justified without chronic intracranial recording when specific criteria for focal scalp-sphenoidal ictal EEG onsets are met, localized hypometabolism predominantly involves the same temporal lobe, and no other conflicting information has been obtained from additional tests of focal functional deficit, structural imaging, or seizure semiology.     

Dipole modeling of scalp electroencephalogram epileptic discharges: correlation with intracerebral fields.

OBJECTIVE: In order to evaluate the feasibility of modeling seizures and the reliability of dipole models, we compared source localizations of scalp seizures with the distribution of simultaneous intracerebral electroencephalogram (SEEG). METHODS: In a first session, only scalp electroencephalogram (EEG) was recorded from 15 patients. We averaged the first detectable ictal activity in two consecutive segments of stable topography and morphology. Spatio-temporal dipole sources were estimated for each segment and projected on 3D-magnetic resonance images. In a second session, SEEG was recorded simultaneously with control scalp electrodes, allowing the identification of ictal patterns similar to those submitted to dipole modeling. RESULTS: Ictal discharges could be analyzed in only 6 of 15 patients. In the remaining 9, scalp discharges were undetectable or non-reproducible in 6, and solutions were unstable despite an apparently stable discharge in 3. In the 6 patients successfully modeled, dipoles were found in regions where SEEG discharges were present. However, when intracerebral discharges were very focal, there was no corresponding scalp activity. When intracerebral signals were maximal in the mesial temporal regions at the seizure onset, only lateral neocortical dipoles were found. When discharges reached the frontal lobes, we could identify lateral and mesial frontal sources. CONCLUSIONS: In most seizures, it was not possible to obtain satisfactory dipole models, probably a reflection of the high noise level or widespread generators. When modeling was possible, our results suggested that mesial temporal seizure discharges did not contribute to scalp EEG activity. This activity appears to reflect signals synchronized and distributed over the lateral temporal or frontal neocortex, as well as signals generated in mesial frontal areas.     

Periventricular nodular heterotopia: classification, epileptic history, and genesis of epileptic discharges

PURPOSE: Periventricular nodular heterotopia (PNH) is among the most common malformations of cortical development, and affected patients are frequently characterized by focal drug-resistant epilepsy. Here we analyzed clinical, MRI, and electrophysiologic findings in 54 PNH patients to reevaluate the classification of PNH, relate the anatomic features to epileptic outcome, and ascertain the contribution of PNH nodules to the onset of epileptic discharges. METHODS: The patients were followed up for a prolonged period at the Epilepsy Center of our Institute. In all cases, we related MRI findings to clinical and epileptic outcome and analyzed interictal and ictal EEG abnormalities. In one patient, EEG and stereo-EEG (SEEG) recordings of seizures were compared. RESULTS: We included cases with periventricular nodules, also extending to white matter and cortex, provided that anatomic continuity was present between nodules and malformed cortex. Based on imaging and clinical data, patients were subdivided into five PNH groups: (a) bilateral and symmetrical; (b) bilateral single-noduled; (c) bilateral and asymmetrical; (d) unilateral; and (e) unilateral with extension to neocortex. The latter three groups were characterized by worse epileptic outcome. No differences in outcome were found between unilateral PNH patients regardless the presence of cortical involvement. Interictal as well as ictal EEG abnormalities were always related to PNH location. CONCLUSIONS: The distinctive clinical features and epileptic outcomes in each group of patients confirm the reliability of the proposed classification. Ictal EEG and SEEG recordings suggest that seizures are generated by abnormal anatomic circuitries including the heterotopic nodules and adjacent cortical areas.     

Differential contribution of excitatory and inhibitory neurons in shaping neurovascular coupling in different epileptic neural states

Understanding the neurovascular coupling (NVC) underlying hemodynamic changes in epilepsy is crucial to properly interpreting functional brain imaging signals associated with epileptic events. However, how excitatory and inhibitory neurons affect vascular responses in different epileptic states remains unknown. We conducted real-time in vivo measurements of cerebral blood flow (CBF), vessel diameter, and excitatory and inhibitory neuronal calcium signals during recurrent focal seizures. During preictal states, decreases in CBF and arteriole diameter were closely related to decreased γ-band local field potential (LFP) power, which was linked to relatively elevated excitatory and reduced inhibitory neuronal activity levels. Notably, this preictal condition was followed by a strengthened ictal event. In particular, the preictal inhibitory activity level was positively correlated with coherent oscillating activity specific to inhibitory neurons. In contrast, ictal states were characterized by elevated synchrony in excitatory neurons. Given these findings, we suggest that excitatory and inhibitory neurons differentially contribute to shaping the ictal and preictal neural states, respectively. Moreover, the preictal vascular activity, alongside with the γ-band, may reflect the relative levels of excitatory and inhibitory neuronal activity, and upcoming ictal activity. Our findings provide useful insights into how perfusion signals of different epileptic states are related in terms of NVC.     

Ictal and interictal SPECT findings in childhood absence epilepsy.

The purpose of this study was to investigate the informative value of single photon emission tomography (SPECT) in relation to the pathophysiological functioning of the brain during absence seizures and the origin of ictal discharges in idiopathic generalized epilepsies (IGEs). Six patients with childhood absence epilepsy (CAE) were selected for the study and two consecutive SPECT sessions were performed concomitant with EEG recordings revealing normal results and during hyperventilation (HV) studies where the ictal discharges were induced either alone or accompanied by clinical absence seizures. All six patients had ictal discharges in their EEGs during HV and two of them also had clinical absences. SPECT findings during HV revealed an overall increase in the cerebral blood flow (CBF) with significantly higher values as compared to the baseline data. There was no indication for any focal origin in either the interictal or the ictal SPECT findings. Results of the study were supportive for the concept of subcortical origin for the absence seizures and they were also promising for the diagnostic value of ictal SPECT in epileptic cases with undetermined origin as to whether they were localization-related or generalized.     

EEG-fMRI study of the ictal and interictal epileptic activity in patients with eyelid myoclonia with absences

Purpose: To investigate the blood oxygenation level‐dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography‐correlated functional magnetic resonance imaging (EEG‐fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function. Methods: Four patients with EMA were investigated through the method of EEG‐fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored. Results: Seven sessions of EEG‐fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges. Conclusions: The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations (“default” pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.     

Planned ictal FDG PET imaging for localization of extratemporal epileptic foci

PURPOSE: This work demonstrates the feasibility of planned ictal positron emission tomography (PET) with [18F]fluoro-2-deoxy-glucose (FDG) for localization of epileptic activity in patients with frequent partial seizures of extratemporal origin. METHODS: Ictal PET imaging was performed in four patients (two men and two women, ages 28-61) with continuous or very frequent (every 3-15 min) partial seizures. All patients had abnormalities apparent on magnetic resonance (MR) or computed tomographic (CT) imaging, two with extensive brain lesions that precluded precise localization of the seizure focus with interictal PET or single-photon emission tomography (SPECT) imaging. RESULTS: Ictal PET imaging demonstrated a restricted area of focal hypermetabolism concordant with surface electroencephalographic (EEG) recording in all cases. The PET images were registered to MR imaging data for further anatomic localization of hypermetabolic regions in three cases. The ictal PET data were used to guide neurosurgical intervention in one case. CONCLUSIONS: We conclude that planned ictal PET imaging may be a useful and potentially superior approach to ictal SPECT for identifying the epileptic focus in a selected group of patients with continuous or frequent simple partial seizures.     

Temporal lobe or psychomotor status epilepticus. A case report

A 22-year-old female with a history of polymorphic and uncontrollable psychomotor seizures in association with unclear disturbances of perception, emotion and intellect is reported. During chronically performed SEEG studies the patient entered a psychomotor status epilepticus with transition from the discontinuous to the continuous type. The electrical findings at surface and depth indicated a primary epileptogenic area in the right hippocampal formation. The typical clinical signs were observed during depth recording. The anatomo-electroclinical correlations therefore could be studied with confidence. Good correlation could be established between distinct seizure patterns and predominant clinical signs. Especially long-lasting hallucinations of music were clearly linked to the ictal involvement of the right gyrus of Heschl, and clouded consciousness and/or memory disturbances were shown to be due to bilateral ictal discharges in the hippocampal formations. Attempts to control the status activity by diazepam intravenously were without striking effects, but very specific acoustic stimuli influenced the discharging pattern of the gyrus of Heschl.     

Changes preceding interictal epileptic EEG abnormalities: comparison between EEG/fMRI and intracerebral EEG

Purpose: In simultaneous scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), blood oxygen level dependent (BOLD) changes occurring before the spike have been sometimes described but could not be explained. To characterize the origin of this prespike BOLD signal change, we looked for electrographic changes in stereo‐EEG (SEEG) possibly preceding the scalp spike in patients that showed early BOLD response in EEG/fMRI. Methods: We studied four patients with drug‐resistant focal epilepsy who underwent EEG/fMRI, showed a prespike BOLD response, and were then studied with depth electrodes for presurgical localization of the epileptic generator. Early BOLD responses in the region of the spike field were analyzed using models with hemodynamic response functions (HRFs) peaking from −9 to +9 s around the spike. SEEG recordings in the period and location corresponding to the early HRF responses were analyzed to detect if electrographic changes were present in the SEEG before the scalp abnormality. Key Findings: One of the four patients presented a SEEG interictal discharge in the period corresponding to the early BOLD response. In the other three, no electrographic changes were detected in the SEEG in the period corresponding to early BOLD changes. Significance: Although the early BOLD activity may sometimes be explained by a synchronized neural discharge detectable with SEEG but not visible on the scalp EEG, in most cases the early BOLD response reflects a metabolic phenomenon that does not appear to result from a synchronized neuronal discharge. Prespike metabolic responses can result from synchronized or nonsynchronized neuronal activity, or from nonneuronal mechanisms including glia.     

Long-term video-EEG recordings following transient unilateral middle cerebral and common carotid artery occlusion in Long-Evans rats

The mechanisms of injured brain that establish poststroke seizures and epilepsy are not well understood, largely because animal modeling of these phenomena has had limited development. We studied the electrobehavioral properties of 2.5-month-old male Long-Evans rats by video-electroencephalogram (EEG) recordings during the 6 months following sham operation or lesioning by transient unilateral middle cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAO). The main findings of this study were: (1) control animals demonstrated interictal focal or restricted bilateral 7-8 Hz spike-wave discharges (SWDs) lasting 1-2 s without behavioral change and ictal generalized 7-8 Hz SWDs (absence seizures), which were prolonged, frequent, and associated with motor arrest of the animal; (2) lesioned animals demonstrated cortical infarction associated with interictal SWDs similar to controls, except that focal discharges were more numerous relative to bilateral discharges, and ictal SWDs, which were of shorter duration and less frequent than those of controls; (3) lesioned animals demonstrated decreased hemispheric and regional spectral power at approximately 7 and 15 Hz compared with controls, directly related to the reduced occurrence of ictal SWDs; and (4) lesioning did not independently generate either focal or generalized epileptic seizures. These studies demonstrate distinct electrobehavioral properties of Long-Evans rats lesioned by MCA/CCAO as juveniles and monitored by video-EEG recordings during young adulthood but fail to provide evidence of poststroke seizures or epilepsy.     

Effect of Seizures on Cerebral Blood Flow Measured with 15–H2O and Positron Emission Tomography

Summary: To study quantitative alterations in regional cerebral blood flow (rCBF) accompanying seizures, and to assess the utility of ictal activation PET scanning as a noninvasive clinical tool for localization of epileptogenic foci, we used pentylenetetrazole (F'TZ) to induce seizures during ¹⁵O-water positron emission tomography (PET) CBF measurement in 15 patients with uncontrolled complex partial seizures (CPS) who had been referred for surgical evaluation. Continuous EEG monitoring was performed during the PET scans. After baseline scans were obtained, each patient was injected with 150–300 mg PTZ. Two patients had generalized tonic-clonic seizures (GTCs). CBF increases were asymmetrical. Two patients (in 1 the seizure occurred spontaneously, without PTZ injection) who had CPS had bitemporal 70–80% increases in CBF. Thalamic CBF increased during both CPS and GTCS. Five patients had an increase in focal EEG in-terictal abnormality, accompanied by focal flow decreases in 3. PTZ injection not accompanied by clinical seizures did not increase CBF. Partial seizures may be associated with bilateral increases in CBF, and subcortical gray regions are involved in ictal activation.