Depth Electrode Recordings Research Articles

Initiation, Propagation, and Termination of Partial (Focal) Seizures

The neurophysiological patterns that correlate with partial (focal) seizures are well defined in humans by standard electroencephalogram (EEG) and presurgical depth electrode recordings. Seizure patterns with similar features are reproduced in animal models of partial seizures and epilepsy. However, the network determinants that support interictal spikes, as well as the initiation, progression, and termination of seizures, are still elusive. Recent findings show that inhibitory networks are prominently involved at the onset of these seizures, and that extracellular changes in potassium contribute to initiate and sustain seizure progression. The end of a partial seizure correlates with an increase in network synchronization, which possibly involves both excitatory and inhibitory mechanisms.

MTLE with hippocampal sclerosis in adult as a syndrome

Mesial temporal lobe epilepsy with hippocampal sclerosis, (MTLE-HS) is a well characterized disorder which associates electroclinical features suggestive of seizure onset in the mesial or limbic structures of the temporal lobe, and hippocampal sclerosis. This underlying pathology differentiates MTLE-HS from MTLE due to other pathological substrates. Typically, when MTLE-HS is diagnosed, a typical course of the disease can be retrospectively recognized, including early prolonged febrile seizures, a latent period, onset in mid-to-late childhood, auras that may initially occur in isolation, periods of seizure remission during adolescence or early adulthood. Then the condition progresses, associating elaborated seizures, progressive drug-resistance and cognitive, mainly memory, disorders of variable intensity. The seizures have a relatively gradual onset/offset, developing over 1–2minutes, with partial awareness at the onset, and lasting for 2 to 10minutes. Auras are common, with visceral, autonomic, psycho-affective, experiential components, presenting less frequently diverse sensory or sensorial symptoms. Awareness is generally preserved at onset, but then loss of consciousness occurs, with initial motionless stare, and automatisms, which typically are oro-alimentary, vocal or gestural, accompanied by motor signs such as contralateral dystonic posturing. A dysphasia is frequent when the focus is in the dominant hemisphere, often prolonged by a post-ictal dysphasia and confusion. Interictal EEG shows anterior or mid-temporal spikes/sharp ipsilaterally to the focus, in combination with non-epileptiform regional slowing. These changes may be bilateral but usually predominates ipsilaterally. Ictal EEG changes are marked by rhythmic temporal alpha or theta activity within 30seconds of clinical onset. The hallmark is the presence of hippocampal sclerosis, demonstrable on coronal MRI sequences by unilateral (or asymmetrical) decrease in hippocampal volume and increase in signal on T2-weighted sequences. The diagnosis of MTLE is crucial because of its frequent poor prognosis under antiepileptic drugs, and of the possibility of excellent results after resective surgery. PET scanning shows a typical antero-mesial hypometabolism extending to the pole and lateral aspects of the temporal lobe. Presurgical investigations may also include depth-electrode recordings in case of doubt about more extensive or bilateral onsets. They demonstrate and lateralize the amygdalo-hippocampal discharges, some of them remaining apparently asymptomatic in the absence of extrahippocampal spreading. These interactions between hippocampal and extrahippocampal networks confer its specificity to MTLE-HS, together with its remarkable natural course. This entity is diagnostically essential, whether it should be regarded as an epileptic syndrome, disease or a distinctive constellation.

Cortical involvement in focal epilepsies with epileptic spasms

The pathophysiological mechanisms of epileptic spasms are still poorly understood. The role of subcortical structures has been suggested on the basis of non-localized EEG features and from experimental data. The description of asymmetric spasms associated with lateralized EEG patterns has challenged this view and raises the possibility of a cortical origin. This study investigated the cortical organization of partial seizures associated with epileptic spasms in children undergoing intracerebral EEG recordings for presurgical evaluation. Eleven children with drug resistant epileptic spasms and for whom depth electrode recordings were performed were retrospectively studied. In all children several features suggested a focal origin. Cortical involvement was studied using the "Epileptogenicity Index" (EI). A focal origin was finally demonstrated in 10/11 patients. Seven patients demonstrated pre-ictal changes in the seizure onset zone area. EI analysis showed maximal values in the temporal (n=5), parietal (n=1) or frontal (n=5) cortices. EEG changes were also observed in the premotor cortex during spasms in patients with frontal or parietal seizures and in 3/5 patients with temporal lobe seizures. Good surgical outcome (class I or II) was obtained in 7/10 patients. Seizures associated with epileptic spasms may originate from various cortical regions. Premotor/motor cortices are probably involved in determining ictal clinical changes.

Ictal propagation of high frequency activity is recapitulated in interictal recordings: Effective connectivity of epileptogenic networks recorded with intracranial EEG

Seizures are increasingly understood to arise from epileptogenic networks across which ictal activity is propagated and sustained. In patients undergoing invasive monitoring for epilepsy surgery, high frequency oscillations have been observed within the seizure onset zone during both ictal and interictal intervals. We hypothesized that the patterns by which high frequency activity is propagated would help elucidate epileptogenic networks and thereby identify network nodes relevant for surgical planning. Intracranial EEG recordings were analyzed with a multivariate autoregressive modeling technique (short-time direct directed transfer function—SdDTF), based on the concept of Granger causality, to estimate the directionality and intensity of propagation of high frequency activity (70–175Hz) during ictal and interictal recordings. These analyses revealed prominent divergence and convergence of high frequency activity propagation at sites identified by epileptologists as part of the ictal onset zone. In contrast, relatively little propagation of this activity was observed among the other analyzed sites. This pattern was observed in both subdural and depth electrode recordings of patients with focal ictal onset, but not in patients with a widely distributed ictal onset. In patients with focal ictal onsets, the patterns of propagation recorded during pre-ictal (up to 5min immediately preceding ictal onset) and interictal (more than 24h before and after seizures) intervals were very similar to those recorded during seizures. The ability to characterize epileptogenic networks from interictal recordings could have important clinical implications for epilepsy surgery planning by reducing the need for prolonged invasive monitoring to record spontaneous seizures.

Detection of Spreading Depolarization with Intraparenchymal Electrodes in the Injured Human Brain

Spreading depolarization events following ischemic and traumatic brain injury are associated with poor patient outcome. Currently, monitoring these events is limited to patients in whom subdural electrodes can be placed at open craniotomy. This study examined whether these events can be detected using intra-cortical electrodes, opening the way for electrode insertion via burr hole. Animal work was carried out on adult Sprague-Dawley rats in a laboratory setting to investigate the feasibility of recording depolarization events. Subsequently, 8 human patients requiring craniotomy for traumatic brain injury or aneurysmal subarachnoid hemorrhage were monitored for depolarization events in an intensive care setting with concurrent strip (subdural) and depth (intra-parenchymal) electrode recordings. (1) Depolarization events can be reliably detected from intra-cortically placed electrodes. (2) A reproducible slow potential change (SPC) waveform morphology was identified from intra-cortical electrodes on the depth array. (3) The depression of cortical activity known to follow depolarization events was identified consistently from both intra-cortical and sub-cortical electrodes on the depth array. Intra-parenchymally sited electrodes can be used to consistently identify depolarization events in humans. This technique greatly extends the capability of monitoring for spreading depolarization events in injured patients, as electrodes can be sited without the need for craniotomy. The method provides a new investigative tool for the evaluation of the contribution of these events to secondary brain injury in human patients.

Are high frequency oscillations associated with altered network topology in partial epilepsy?

Neurophysiological studies have reported functional network alterations in epilepsy, most consistently in the theta frequency band. Highly interconnected brain regions (so-called ‘hubs’) seem to be important in these epileptic networks. High frequency oscillations (HFOs) in intracranial EEG recordings are recently discovered biomarkers that can identify the epileptogenic area and are thought to result from altered neuronal interactions. We studied whether the epileptogenic zone (identified by HFOs and seizure onset zone) is associated with pathological hubs. Bilateral depth electrode recordings from the hippocampus and amygdala were available from twelve patients suspected of temporal lobe epilepsy. HFOs, classified as ripples (80–250Hz) and fast ripples (250–500Hz), and epileptiform spikes were marked for all patients in a five-minute epoch of slow-wave sleep. For each channel, we computed hub-measures from a period without epileptiform spikes and found that the epileptogenic zone was associated with a decreased hub-value in the theta frequency band. The amount of HFOs, especially fast ripples, was negatively correlated with the hub-value per channel. Results from post-hoc analyses of other frequency bands, particularly the broad- and gamma frequency band, pointed in the same direction as the results for the theta frequency band. These findings suggest a pathological functional ‘isolation’ of the epileptogenic zone in the interictal state.

A statistical method for predicting seizure onset zones from human single-neuron recordings

Objective. Clinicians often use depth-electrode recordings to localize human epileptogenic foci. To advance the diagnostic value of these recordings, we applied logistic regression models to single-neuron recordings from depth-electrode microwires to predict seizure onset zones (SOZs). Approach. We collected data from 17 epilepsy patients at the Barrow Neurological Institute and developed logistic regression models to calculate the odds of observing SOZs in the hippocampus, amygdala and ventromedial prefrontal cortex, based on statistics such as the burst interspike interval (ISI). Main results. Analysis of these models showed that, for a single-unit increase in burst ISI ratio, the left hippocampus was approximately 12 times more likely to contain a SOZ; and the right amygdala, 14.5 times more likely. Our models were most accurate for the hippocampus bilaterally (at 85% average sensitivity), and performance was comparable with current diagnostics such as electroencephalography. Significance. Logistic regression models can be combined with single-neuron recording to predict likely SOZs in epilepsy patients being evaluated for resective surgery, providing an automated source of clinically useful information.

Interictal PET and ictal subtraction SPECT: Sensitivity in the detection of seizure foci in patients with medically intractable epilepsy

Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. Fifty-three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7 years (median 32 years, range 1-60 years). Twenty-seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty-three patients had surgical resection and >2 years of follow-up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.

Increased Ictal Discharge Frequency and Neocortex Gliosis in Lateral Temporal Lobe Epilepsy

Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis has both a scalp EEG initial ictal discharge frequency, which is faster, and also an intracranial EEG onset site that is more restricted to the hippocampus, than lateral TLE without hippocampal sclerosis. This study was performed to determine if lateral TLE patients have either intracranial EEG neocortical initial ictal frequencies or measures of lateral neocortex (LNC) histopathology that differ from patients whose seizures start in medial or multiple temporal lobe areas. Thirty-six TLE patients undergoing ictal depth and subdural strip electrode recordings were studied to determine the initial ictal discharge site (epileptogenic zone) within the temporal lobe and neocortical ictal frequency. In 25 patients, the number of reactive astrocytes in the neocortex and other measures of pathologic assessment of LNC were assessed. The initial neocortical ictal frequency was significantly faster when the initial ictal discharge was in the LNC ± medial paleocortex than either when it was in the hippocampus ± medial paleocortex or when it occurred simultaneously over the entire temporal lobe. Intracortical and Chaslin gliosis were both significantly greater when the initial ictal discharge was limited to the LNC than when it was in the hippocampus and/or medial paleocortex. Temporal lobe seizures originating in neocortex had a faster initial neocortical ictal frequency than seizures arising either medially in the hippocampus or widely over the whole temporal lobe. Epileptogenic zones limited to temporal neocortex were associated with greater intraneocortical and Chaslin gliosis compared with zones confined to medial structures.

Mapping Human Pitch Representation in a Distributed System Using Depth-Electrode Recordings and Modeling

Depth-electrode recordings from the auditory cortex of humans undergoing presurgical evaluation for epilepsy allow the recording of ensemble responses to pitch in the form of local field potentials. These recordings allow another test of the hypothesis that there is a specialized neural ensemble for pitch within auditory cortex. Moreover, the technique allows recordings from multiple sites with millisecond temporal resolution to allow modeling of the effective connectivity between these sites. Here we argue that this takes the form of a hierarchical network of pitch-sensitive regions. Activity can be understood as reflecting predictive coding, in which perceptual predictions and error messages are continuously exchanged between a higher pitch center and lower-level auditory cortex.

1H-MRS Imaging in Patients with Non-Lesional Insular Cortex Epilepsy Characterized by Depth Electrode Recordings (P01.058)

Objective: Identifying insular metabolic abnormalities using proton magnetic resonance spectroscopy imaging (1H-MRSI) during the presurgical evaluation of non-lesional insular cortex epilepsy (ICE). Background Seizures arising from the insular cortex can generate a wide variety of ictal symptoms potentially leading to a false diagnosis of temporal, frontal or parietal lobe epilepsy. In non-lesional ICE, standard non-invasive investigations such as video-EEG, SPECT and PET are often non-localizing or false-localizing potentially leading to inaccurate localization of the epileptogenic zone. Design/Methods: Using voxel-based 1H-MRSI, we studied 16 patients with suspected non-lesional ICE, 13 of which subsequently underwent insular and peri-insular depth electrode recordings, as well as 16 age-matched controls. Four voxels (8 ml each) were positioned to include bilateral anterior and posterior insular regions. Spectral analysis was performed to quantitate N-acetylaspartate (NAA) and creatinine (Cr). Comparisons of the NAA/Cr ratios between the normal and affected insula and between patients and controls were made using a one-way ANOVA. An asymmetry index (AI) was also calculated to evaluate intra-individual metabolic variations. Results: Insular interictal spikes (IIS) were recorded in 12 of 13 patients on intracerebral EEG recordings. Insular seizures were recorded in 6 of those patients (ICE). Ipsilateral and contralateral NAA/Cr ratios were found to be similar in all the groups. No difference in NAA/Cr ratios was found between ICE patients, IIS patients and healthy controls (2.05 ± 0.20, 2.16 ± 0.21 and 2.01 ± 0.16 respectively, P=0.06). Mean AIs in ICE and IIS patients were non-significant when compared to controls (P=0.17). Lateralization of the AI to the epileptic insular cortex was found in only one of 1 of 6 (17%) ICE patients. Conclusions: 1H-MRSI failed to identify significant metabolic abnormalities in patients with insular spikes and/or seizures and is hence unlikely to be useful during the presurgical evaluation of suspected ICE. Supported by: Quebec Bio-Imaging Network (QBIN) and the Savoy Foundation. Disclosure: Dr. Gibbs has nothing to disclose. Dr. Boulanger has nothing to disclose. Dr. Gilbert has nothing to disclose. Dr. Leroux has nothing to disclose. Dr. Bouthillier has nothing to disclose. Dr. Nguyen has nothing to disclose.

Seizure Outcome and Memory Function after Multiple Hippocampal Transections (IN5-1.009)

Objective: To evaluate seizure outcome and memory function after multiple hippocampal transections (MHT) of the hippocampus in intractable nonlesional mesial temporal lobe epilepsy (MTLE). Background Hippocampal anatomy suggests that the circuits of memory processing (transverse lamellae) are different from those of seizure propagation (longitudinal pathways). Thus, transverse cuts may interrupt seizure circuitry without interfering with memory function. Design/Methods: 13 patients with nonlesional MTLE had depth electrode recordings confirming hippocampal seizure onset and underwent MHT. Duration of epilepsy ranged between 5 and 55 years. Antiepileptic drugs (AEDs) were not changed postoperatively. Intraoperative monitoring was done with 5-6 hippocampal electrodes spaced at around 1 cm intervals, and spike counting for approximately 10 minutes before each cut. The number of transections ranged between 4 and 7 resulting in marked spike reduction (p=0.003, paired t-test). Neuropsychological assessment was done preoperatively and 1 year postoperatively in all patients. Results: There were no complications. 10 patients (77%) are seizure-free (follow-up>1 year in 8 patients, and 0.3). Conclusions: MHT provides an effective intervention and a safer alternative than temporal lobectomy regarding memory preservation in patients with nonlesional MTLE. Disclosure: Dr. Kahriman has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Macinuas has nothing to disclose. Dr. Bailey has nothing to disclose. Dr. Fastenau has nothing to disclose. Dr. Syed has nothing to disclose. Dr. Amina has nothing to disclose. Dr. Tanner has received personal compensation for activities with GlaxoSmithKline, Inc. as a speaker. Dr. Karanec has nothing to disclose. Dr. Luders has nothing to disclose. Dr. Koubeissi has received personal compensation for activities with UCB Pharma and Pfizer Inc as a speaker.

Poster #134 GAMMA OSCILLATIONS IN MEG-DATA IN CHRONIC SCHIZOPHRENIA AND DURING KETAMINE ADMINISTRATION: EVIDENCE FOR THE ROLE OF NMDA-RECEPTOR DEFICITS IN THE PATHOPHYSIOLOGYOF SCHIZOPHRENIA

We have previously used direct electrode recordings in two human subjects to identify neural correlates of the perception of pitch (Griffiths, Kumar, Sedley et al., Direct recordings of pitch responses from human auditory cortex, Curr. Biol. 22 (2010), pp. 1128–1132). The present study was carried out to assess virtual-electrode measures of pitch perception based on non-invasive magnetoencephalography (MEG). We recorded pitch responses in 13 healthy volunteers using a passive listening paradigm and the same pitch-evoking stimuli (regular interval noise; RIN) as in the previous study. Source activity was reconstructed using a beamformer approach, which was used to place virtual electrodes in auditory cortex. Time-frequency decomposition of these data revealed oscillatory responses to pitch in the gamma frequency band to occur, in Heschl's gyrus, from 60 Hz upwards. Direct comparison of these pitch responses to the previous depth electrode recordings shows a striking congruence in terms of spectrotemporal profile and anatomical distribution. These findings provide further support that auditory high gamma oscillations occur in association with RIN pitch stimuli, and validate the use of MEG to assess neural correlates of normal and abnormal pitch perception.

Poster #133 DECREASED ATTENTION TO INFORMATIVE SOCIAL CUES IN SCHIZOPHRENIA PATIENTS

We have previously used direct electrode recordings in two human subjects to identify neural correlates of the perception of pitch (Griffiths, Kumar, Sedley et al., Direct recordings of pitch responses from human auditory cortex, Curr. Biol. 22 (2010), pp. 1128–1132). The present study was carried out to assess virtual-electrode measures of pitch perception based on non-invasive magnetoencephalography (MEG). We recorded pitch responses in 13 healthy volunteers using a passive listening paradigm and the same pitch-evoking stimuli (regular interval noise; RIN) as in the previous study. Source activity was reconstructed using a beamformer approach, which was used to place virtual electrodes in auditory cortex. Time-frequency decomposition of these data revealed oscillatory responses to pitch in the gamma frequency band to occur, in Heschl's gyrus, from 60 Hz upwards. Direct comparison of these pitch responses to the previous depth electrode recordings shows a striking congruence in terms of spectrotemporal profile and anatomical distribution. These findings provide further support that auditory high gamma oscillations occur in association with RIN pitch stimuli, and validate the use of MEG to assess neural correlates of normal and abnormal pitch perception.

Transient Suppression of Broadband Gamma Power in the Default-Mode Network Is Correlated with Task Complexity and Subject Performance

Task performance is associated with increased brain metabolism but also with prominent deactivation in specific brain structures known as the default-mode network (DMN). The role of DMN deactivation remains enigmatic in part because its electrophysiological correlates, temporal dynamics, and link to behavior are poorly understood. Using extensive depth electrode recordings in humans, we provide first electrophysiological evidence for a direct correlation between the dynamics of power decreases in the DMN and individual subject behavior. We found that all DMN areas displayed transient suppressions of broadband gamma (60-140 Hz) power during performance of a visual search task and, critically, we show for the first time that the millisecond range duration and extent of the transient gamma suppressions are correlated with task complexity and subject performance. In addition, trial-by-trial correlations revealed that spatially distributed gamma power increases and decreases formed distinct anticorrelated large-scale networks. Beyond unraveling the electrophysiological basis of DMN dynamics, our results suggest that, rather than indicating a mere switch to a global exteroceptive mode, DMN deactivation encodes the extent and efficiency of our engagement with the external world. Furthermore, our findings reveal a pivotal role for broadband gamma modulations in the interplay between task-positive and task-negative networks mediating efficient goal-directed behavior and facilitate our understanding of the relationship between electrophysiology and neuroimaging studies of intrinsic brain networks.

Gamma band pitch responses in human auditory cortex measured with magnetoencephalography

We have previously used direct electrode recordings in two human subjects to identify neural correlates of the perception of pitch (Griffiths, Kumar, Sedley et al., Direct recordings of pitch responses from human auditory cortex, Curr. Biol. 22 (2010), pp. 1128–1132). The present study was carried out to assess virtual-electrode measures of pitch perception based on non-invasive magnetoencephalography (MEG). We recorded pitch responses in 13 healthy volunteers using a passive listening paradigm and the same pitch-evoking stimuli (regular interval noise; RIN) as in the previous study. Source activity was reconstructed using a beamformer approach, which was used to place virtual electrodes in auditory cortex. Time-frequency decomposition of these data revealed oscillatory responses to pitch in the gamma frequency band to occur, in Heschl's gyrus, from 60 Hz upwards. Direct comparison of these pitch responses to the previous depth electrode recordings shows a striking congruence in terms of spectrotemporal profile and anatomical distribution. These findings provide further support that auditory high gamma oscillations occur in association with RIN pitch stimuli, and validate the use of MEG to assess neural correlates of normal and abnormal pitch perception.

High-frequency (80–500 Hz) oscillations and epileptogenesis in temporal lobe epilepsy

High-frequency oscillations (HFOs), termed ripples (80–200Hz) and fast ripples (250–600Hz), are recorded in the EEG of epileptic patients and in animal epilepsy models; HFOs are thought to reflect pathological activity and seizure onset zones. Here, we analyzed the temporal and spatial evolution of interictal spikes with and without HFOs in the rat pilocarpine model of temporal lobe epilepsy. Depth electrode recordings from dentate gyrus (DG), CA3 region, subiculum and entorhinal cortex (EC), were obtained from rats between the 4th and 15th day after a status epilepticus (SE) induced by i.p. injection of pilocarpine. The first seizure occurred 6.1±2.5days after SE (n=7 rats). Five of 7 animals exhibited interictal spikes that co-occurred with fast ripples accounting for 4.9±4.6% of all analyzed interictal spikes (n=12,886) while all rats showed interictal spikes co-occurring with ripples, accounting for 14.3±3.4% of all events. Increased rates of interictal spikes without HFOs in the EC predicted upcoming seizures on the following day, while rates of interictal spikes with fast ripples in CA3 reflected periods of high seizure occurrence. Finally, interictal spikes co-occurring with ripples did not show any specific relation to seizure occurrence. Our findings identify different temporal and spatial developmental patterns for the rates of interictal spikes with or without HFOs in relation with seizure occurrence. These distinct categories of interictal spikes point at dynamic processes that should bring neuronal networks close to seizure generation.

Heterotopia Associated with Hippocampal Sclerosis: An Under-Recognized Cause of Early Onset Epilepsy in Children Operated on for Temporal Lobe Epilepsy

The aim of this study is to report on 52 children operated on for pharmacoresistant temporal lobe epilepsy, with special emphasis on histopathology and correlation with clinical features. Charts were retrospectively analyzed. All children underwent comprehensive clinical, electrophysiological and radiological investigations before surgery. Surgical procedures were tailored according to scalp, foramen ovale and eventually depth electrode recordings. Histopathology was compared with clinical variables (χ (2) and Fisher's exact tests). Outcome was evaluated using the Engel scale. Developmental tumor was found in 14 cases, malformation of cortical development (MCD) in 26, isolated hippocampal sclerosis (HS) in 5 and gliosis in 7. Dual pathology (DP) affected 18 patients and the main extrahippocampal lesion consisted of microscopic sub-cortical heterotopias (HS-HT) for 15 patients who shared a particular clinical pattern: a history of febrile seizures (FS) and/or brain injury, early onset of epilepsy without latent period from FS to the first temporal seizure, and a particularly good outcome following surgery. In our pediatric temporal lobe surgery series, the prevalence for MCD and for DP was higher than in adult series. Age at seizure onset depends on pathology, and is earlier when involving the neocortex rather than only the hippocampus. We identify the association HS-HT (the most frequent DP in this series), with particular clinical features.

Insular epilepsy masquerading as multifocal cortical epilepsy as proven by depth electrode

The insular cortex is an uncommon epileptogenic location from which complex partial seizures may arise. Seizure activity in insular epilepsy may mimic temporal, parietal, or other cortical areas. Semiology, electroencephalography, and even surface electrocorticography recordings may falsely localize other cortical foci, leading to inaccurate diagnosis and treatment. The use of insular depth electrodes allows more precise localization of seizure foci. The authors describe the case of a young girl with seizures falsely localized to the cortex, with foci arising from the insula, as proven by depth electrode recordings. Resection of the insula yielded seizure control.

Experimental Neonatal Status Epilepticus and the Development of Temporal Lobe Epilepsy with Unilateral Hippocampal Sclerosis

Hippocampal sclerosis is a common pathological finding in patients with temporal lobe epilepsy, including children, but a causal relationship to early-life seizures remains in question. Neonatal status epilepticus in animals can result in neuronal death within the hippocampus, although macroscopic features of hippocampal shrinkage are not evident at adulthood. Here, we examined electrophysiological and pathological consequences of focally evoked status epilepticus triggered by intra-amygdala microinjection of kainic acid in postnatal day 10 rat pups. Neonatal status epilepticus resulted in extensive neuronal death in the ipsilateral hippocampal CA1 and CA3 subfields and hilus, as assessed by DNA fragmentation and Fluoro-Jade B staining 72 hours later. The contralateral hippocampus was not significantly damaged. Histopathology at P55/P65 revealed unilateral hippocampal sclerosis (grade IV, modified Wyler/Watson scale) comprising >50% CA1 and CA3 neuron loss and astrogliosis. Additional features included hydrocephalus ex vacuo, modest dentate granule cell layer widening, and altered neuropeptide Y immunoreactivity indicative of synaptic rearrangement. Hippocampal atrophy was also evident on magnetic resonance imaging. Depth electrode recordings at adulthood detected spontaneous seizures that involved the ipsilateral hippocampus and amygdala. A significant positive correlation was found between hippocampal pathology grade and both frequency and duration of epileptic seizures at adulthood. The current study demonstrates that experimental neonatal status epilepticus can result in classical unilateral hippocampal sclerosis and temporal lobe epilepsy.