Neocortical Temporal Lobe Epilepsy Research Articles

1135 Classification of Temporal Lobe Epilepsy Anatomo-clinico-electrical Hypotheses: A Stereo EEG Study

INTRODUCTION: Temporal lobe epilepsy (TLE) has historically been divided into mesial and lateral (neocortical) TLE, but electrophysiological, semiological, and anatomical evidence indicate that the epileptogenic zone (EZ) and areas of propagation involve both temporal and extratemporal structures. Hypothesis-driven, structured interrogation is crucial for a successful stereo EEG (SEEG) exploration and subsequent successful surgical intervention. METHODS: 59 patients (ages 19-77) with drug-resistant TLE underwent SEEG at our institution from 2020-2022. We retrospectively reviewed each patient’s multidisciplinary discussions, history, imaging, and outcomes. We proposed four types of implantation hypotheses: temporal, temporal/basal/occipital, anterior perisylvian, and perisylvian. We quantitatively validated these types against anatomic coverage and semiology using unsupervised clustering and clinically by comparing classification to rates of successful localization of the epileptogenic zone (EZ) and seizure outcomes. RESULTS: Temporal (only) hypotheses were the least frequent (13.6%), followed by temporal/basal/occipital (25.4%), anterior perisylvian (30.5%), and perisylvian (30.5%). The hypotheses were not different in age at SEEG (p = 0.32), sex (p = 0.67), and handedness (p = 0.33). Frequent semiological features by type were: temporal – autonomic features, dÉjÀ vu; temporal/basal/occipital – visual and language disturbance; anterior perisylvian – oromotor; perisylvian – sensory manifestation. Clustering was validated against semiology (RI = 0.63) and lobar coverage (RI = 0.73). Successful localization of the EZ occurred in 79.7% and did not associate with hypothesis type (p = 0.22). Hypothesis type (p = 0.30) or EZ localization (p = 1.00) did not associate with the presence of an MRI lesion. 6-month Engel 1a rate was 71% and did not vary by hypothesis type (p = 0.29). CONCLUSIONS: The anatomo-clinico-electrical hypotheses in TLE must consider both temporal and extratemporal structures and not be limited by a medial vs. lateral TLE mindset. This proposed classification of TLE hypotheses can serve as starting point for multidisciplinary patient discussion as well as a tool to compare SEEG exploration and outcomes across centers.

Radiofrequency ablation during stereoelectroencephalography: from diagnostic tool to therapeutic intervention. Illustrative case.

Radiofrequency thermocoagulation (RFTC) during intracranial stereoelectroencephalography (sEEG) was first described as a safe technique for creating lesions of epileptic foci in 2004. Since that time, the method has been applied as a diagnostic and/or palliative intervention. Although widely practiced in European epilepsy surgical programs, the technique has not been popularized in the United States given the lack of Food and Drug Administration (FDA)-approved technologies permitting safe usage of in situ sEEG electrodes for this purpose. The authors present a case report of a young female patient with refractory left neocortical temporal lobe epilepsy undergoing sEEG electrode implantation, who underwent sEEG-guided RFTC via a stereotactic temperature-sensing pallidotomy probe. Although used as a diagnostic step in her workup, the patient has remained seizure-free for nearly 18 months. The use of in situ sEEG electrodes for RFTC remains limited in the United States. In this context, this case highlights a safe alternative and temporizing approach to performing diagnostic sEEG-guided RFTC, using a temperature-sensing pallidotomy probe to create small, precise stereotactic lesions. The authors caution careful consideration of this technique as a temporary work-around solution while also highlighting the rising need for new FDA-approved technologies for safe RFTC through in situ temperature-sensing sEEG electrodes.

ID: 218087 RNS for Medically Uncontrolled Bilateral Neocortical Temporal Lobe Epilepsy Confers Favorable Long-Term Seizure Control

Patients with refractory neocortical temporal lobe epilepsy are challenging surgical candidates. Preoperative evaluation often fails to accurately localize SOZs, which necessitates the use of intracranial electroencephalography (iEEG). Furthermore, once SOZ can be defined, patients are typically not candidates for resective surgery. We present a retrospective case series of our experience with diagnosis and management of “bilateral neocortical temporal lobe epilepsy” (bnTLE) treated with responsive neurostimulation (RNS).?

Metabolic profiles and correlation with surgical outcomes in mesial versus neocortical temporal lobe epilepsy.

Differentiating mesial temporal lobe epilepsy (MTLE) and neocortical temporal lobe epilepsy (NTLE) remains challenging. Our study characterized the metabolic profiles between MTLE and NTLE and their correlation with surgical prognosis using 18 F-FDG-PET. A total of 137 patients with intractable temporal lobe epilepsy (TLE) and 40 age-matched healthy controls were recruited. Patients were divided into the MTLE group (N = 91) and the NTLE group (N = 46). 18 F-FDG-PET was used to measure the metabolism of regional cerebra, which was analyzed using statistical parametric mapping. The volume of abnormal metabolism in cerebral regions and their relationship with surgical prognosis were calculated for each surgical patient. The cerebral hypometabolism of MTLE was limited to the ipsilateral temporal and insular lobes (p < 0.001, uncorrected). The NTLE patients showed hypometabolism in the ipsilateral temporal, frontal, and parietal lobes (p < 0.001, uncorrected). The MTLE patients showed extensive hypermetabolism in cerebral regions (p < 0.001, uncorrected). Hypermetabolism in NTLE was limited to the contralateral temporal lobe and cerebellum, ipsilateral frontal lobe, occipital lobe, and bilateral thalamus (p < 0.001, uncorrected). Among patients who underwent resection of epileptic lesions, 51 (67.1%) patients in the MTLE group and 10 (43.5%) in the NTLE group achieved Engel class IA outcome (p = 0.041). The volumes of metabolic increase for the frontal lobe or thalamus in the MTLE group were larger in non-Engel class IA patients than Engel class IA patients (p < 0.05). The spatial metabolic profile discriminated NTLE from MTLE. Hypermetabolism of the thalamus and frontal lobe in MTLE may facilitate preoperative counseling and surgical planning.

Spikes and High Frequency Oscillations in Lateral Neocortical Temporal Lobe Epilepsy: Can They Predict the Success Chance of Hippocampus-Sparing Resections?

PurposeWe investigated the distribution of spikes and HFOs recorded during intraoperative electrocorticography (ioECoG) and tried to elaborate a predictive model for postsurgical outcomes of patients with lateral neocortical temporal lobe epilepsy (TLE) whose mesiotemporal structures are left in situ.MethodsWe selected patients with temporal lateral neocortical epilepsy focus who underwent ioECoG-tailored resections without amygdalo–hippocampectomies. We visually marked spikes, ripples (80–250 Hz), and fast ripples (FRs; 250–500 Hz) on neocortical and mesiotemporal channels before and after resections. We looked for differences in event rates and resection ratios between good (Engel 1A) and poor outcome groups and performed logistic regression analysis to identify outcome predictors.ResultsFourteen out of 24 included patients had a good outcome. The poor-outcome patients showed higher rates of ripples on neocortical channels distant from the resection in pre- and post-ioECoG than people with good outcomes (ppre = 0.04, ppost = 0.05). Post-ioECoG FRs were found only in poor-outcome patients (N = 3). A prediction model based on regression analysis showed low rates of mesiotemporal post-ioECoG ripples (ORmesio = 0.13, pmesio = 0.04) and older age at epilepsy onset (OR = 1.76, p = 0.04) to be predictors of good seizure outcome.ConclusionHFOs in ioECoG may help to inform the neurosurgeon of the hippocampus-sparing resection success chance in patients with lateral neocortical TLE.

HP25: Spikes and HFOs in neocortical temporal lobe epilepsy: Can they help us identify who needs an additional amygdalo-hippocampectomy?

Whether patients with a neocortical temporal lobe epilepsy need an additional amygdalo-hippocampectomy is a frequently asked question in clinical practice. We investigated if spikes and HFOs recorded during intraoperative ECoG (ioECoG) can guide the neurosurgeon in this decision. Methods: We selected patients with a temporal neocortical lesion who underwent an ioECoG-tailored resection without an amygdalo-hippocampectomy from the RESPect database. We visually marked spikes, ripples (80-250Hz) and fast ripples (FRs; 250-500Hz) on neocortical and mesiotemporal channels before and after the resection. We looked for differences in event rates and resection ratios between good (Engel 1A) and poor outcome groups and performed a logistic regression to identify outcome predictors. Results: Fourteen out of 24 included patients had a good outcome. The poor-outcome patients showed a younger age at epilepsy onset (p = 0.01) and higher rates of ripples on neocortical channels distant from the resection in pre- and post-ioECoG (ppre = 0.04, ppost = 0.048). Post-ioECoG FRs were found only in poor-outcome patients (N = 3). Factors predictive for seizure outcome were neocortical and mesiotemporal post-ioECoG ripples (ORneo = 3.68, pneo = 0.055; ORmesio = 0.13, pmesio = 0.03) and age at epilepsy onset (OR = 1.76, p = 0.03). Two poor-outcome patients underwent repeated surgery for removal of mesial structures, but their outcome did not improve. Conclusion: High rates of post-ioECoG ripples distant from the resection and the presence of residual FRs are indicators of an incomplete resection. HFOs in ioECoG may help to inform the neurosurgeon on the chance of success but do not specifically indicate that mesiotemporal structures should additionally be removed.

Chapter 29 - Surgery procedures in temporal lobe epilepsies

Temporal lobe epilepsy (TLE) is the most common cause of refractory epilepsy amenable for surgical treatment and seizure control. Surgery for TLE is a safe and effective strategy. The seizure-free rate after surgical resection in patients with mesial or neocortical TLE is about 70%. Resective surgery has an advantage over stereotactic radiosurgery in terms of seizure outcomes for mesial TLE patients. Both techniques have similar results for safety, cognitive outcomes, and associated costs. Stereotactic radiosurgery should therefore be seen as an alternative to open surgery for patients with contraindications for or with reluctance to undergo open surgery. Laser interstitial thermal therapy (LITT) has also shown promising results as a curative technique in mesial TLE but needs to be more deeply evaluated. Brain-responsive stimulation represents a palliative treatment option for patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior mesial temporal lobe resection. Overall, despite the expansion of innovative techniques in recent years, resective surgery remains the reference treatment for TLE and should be proposed as the first-line surgical modality. In the future, ultrasound therapies could become a credible therapeutic option for refractory TLE patients.

A New Approach to Tumor Cancer with a Novel Imaging Profile for White matter abnormalities including Leukodystrophies: Sensing the Human Brain

Neuromolecular Imaging (NMI) for white matter detection, distinct from that of gray matter is an inventive art. (1) This imaging technique demonstrates, for the first time, a LIVE and continuous videotracking nanotechnology for distinguishing white matter from gray matter in the brain of epilepsy patients, online, in real time and for long periods of time. NMI is known to perform with unrivaled temporal and spatial operational reliability and reproducibility Thus, a nanotechnology for white matter disorders, for example, leukodystrophies, is published for the first time. The purpose of this paper is to present a critical distinction for white versus gray matter in hippocampal and neocortical resected tissue derived from mesial and neocortical temporal lobe epilepsy patients en bloc during intraoperative surgery; the patients present as medically refractory to classical pharmacotherapeutics. The tiny carbon-based lipid polymeric sensor, the BRODERICK PROBE® readily sees white matter in contrast to gray matter in brain neuroanatomic substrates as it continually senses the glia or the neuron, white or gray matter, respectively, with distinct clarity via electroactive signal processing. The difference between white and gray matter is striking as the videotrace slides smoothly from the white to the gray milieu. Thus, a primary in vivo white matter nanotechnology is presented to advance diagnosis and therapy for white and gray matter abnormalities in the brain and spinal cord.

Clinical features of automatisms and correlation with the seizure onset zones: A cluster analysis of 74 surgically-treated cases

ObjectivesTo identify semiologic features of automatisms correlating to different seizure onset zones (SOZ). MethodsIn total, 204 seizures from 74 patients with either oral or manual automatisms were assessed. Patients were divided into four groups depending on the SOZ into frontal, posterior, neocortical temporal, and mesial temporal cortex groups. A k-means analysis was applied on 11 semiologic features on a multi-criteria scale. Then, the resulting clinical patterns were correlated with the SOZs determined by presurgical anatomy-electroclinical data (25 cases with stereo-EEG). ResultsFour clinical patterns of automatisms with different accompanying symptoms were identified. The clinical features of clusters 1 and 4 were mostly found in temporal epilepsy whereas clusters 2 and 3 were more frequent in extratemporal epilepsy. Cluster 1 was significantly correlated with mesial temporal lobe epilepsy (p = .017) and was characterised by aura, postictal confusion, short automatisms delay. Cluster 3 included 1/3 patients with frontal lobe epilepsy and was characterised by emotionality. Cluster 4 was related to neocortical temporal lobe epilepsy and characterised by dystonia and short automatism delay (p = .011). ConclusionThe distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome.

Ictal central apneas in temporal lobe epilepsies

The objective of the study was to examine the frequency and characteristics of ictal central apnea (ICA) in a selective cohort of patients with mesial or neocortical temporal lobe epilepsy (TLE) undergoing surface video-electroencephalography (EEG) and multimodal recording of cardiorespiratory parameters. We retrospectively screened 453 patients who underwent EEG in a single center including nasal airflow measurements, respiratory inductance plethysmography of thoracoabdominal excursions, peripheral capillary oxygen saturation, and electrocardiography. Patients with confirmed TLE subtype, either by magnetic resonance imaging (MRI) lesions limited to the temporal neocortex or mesial structures and concordant neurophysiologic data, or patients who underwent invasive explorations were included. Ictal central apnea frequency and characteristics were analyzed in 41 patients with 164 seizures that had multimodal respiratory monitoring. The total occurrence of ICA in all seizures in this cohort was 79.9%. No significant difference was seen between mesial and neocortical temporal lobe seizures (79.8% and 80.0%, respectively). Ictal central apnea preceded EEG onset by 13 ± 11 s in 33.3% of seizures and was the first clinical sign by 18 ± 14 s in 48.7%. Longer ICA duration trended towards a more severe degree of hypoxemia. In a selective cohort of TLE defined by MRI lesion and/or intracranial recordings, the frequency of ICA was higher than previously reported in the literature. Multimodal respiratory monitoring has localizing value and is generally well tolerated. Ictal central apnea preceded both EEG on scalp recordings as well as clinical seizure onset in a substantial number of patients. Respiratory monitoring and ICA detection is even more paramount during invasive monitoring to confirm that the recorded seizure onset is seen before the first clinical sign.

Optimised induction of on-demand focal hippocampal and neocortical seizures by electrical stimulation

BackgroundEpilepsy is a common neurological disorder affecting over 60 million people globally, approximately a third of whom are refractory to pharmacotherapy. Surgical resection of the epileptogenic zone is frequently unsuitable or ineffective, particularly for individuals with focal neocortical or mesial temporal lobe epilepsy. Therefore, there is a need to develop animal models for elucidating the mechanisms of focal epilepsies and evaluating novel treatment strategies. New MethodWe present two adapted in vivo seizure models, the neocortical and hippocampal epileptic afterdischarge models, that enable stereotyped seizures to be induced on demand by electrical stimulation in anaesthetised, neurologically intact rats. The stimulation parameters and anaesthetic were optimised to generate electrographically reproducible, self-sustaining seizures with a well-defined focal origin. ResultsNeocortical or hippocampal seizures were consistently generated under fentanyl-isoflurane anaesthesia by stimulating the sensorimotor cortex or perforant path, respectively, with 100 Hz trains of biphasic square-wave pulses. The induced seizures were suppressed by propofol, an established antiseizure anaesthetic, thus validating the clinical responsiveness of the developed models. Comparison with Existing MethodsThe high degree of reproducibility in seizure presentation, predictable seizure induction and ability to operate in anaesthetised animals renders these models overall less laborious and more cost-effective than most conventionally used seizure models. ConclusionsThe proposed models provide an efficient method for the high-throughput screening of novel antiseizure therapies, including closed-loop stimulation paradigms, and are well-suited to in vivo investigations that require tight regulation of seizure timing under anaesthetised conditions, particularly neuroimaging studies aimed at understanding the development of epileptogenic networks.

Emotional asymmetries in refractory medial temporal and frontal lobe epilepsy: Their impact on predicting lateralization and localization of seizures

BackgroundEmotional disturbances have been reported in patients with epilepsy. Although conflicting results emanate from relevant studies, depressive symptoms are seen more often in temporal lobe epilepsy (TLE) whereas, hypomanic/manic symptoms usually accompany frontal lobe epilepsy (FLE); the above psychiatric symptoms are especially seen in refractory epilepsy. However, neocortical TLE and medial TLE are considered as distinct epileptic syndromes, and there is limited literature on comparison of affective traits in medial TLE (MTLE) and FLE. AimIn the present study, we sought to investigate affective traits among epilepsy surgery candidates suffering refractory left medial TLE (LMTLE), right medial TLE (RMTLE), left FLE (LFLE), and right FLE (RFLE). ResultsOur results revealed that patients with MTLE scored significantly higher than the ones with FLE in depression, anxiety, asthenia, and melancholia as measured by the Symptoms Rating Scale for Depression and Anxiety (SRSDA), while patients with FLE scored significantly higher in mania than those with MTLE. Moreover, patients with MTLE scored significantly higher than their FLE counterparts on the anxiety scale of the State Trait Personality Inventory (STPI)-trait version. When laterality of the seizure focus was taken into account, no differences were found among both patients with MTLE and patients with FLE, with exception for the Trail Making Test part B (TMT-B) in which patients with RMTLE performed significantly worse than patients with LMTLE. Seizure frequency was higher for FLE. ConclusionsWe provide evidence for an anterior-frontal versus a posterior-medial temporal cerebral functional asymmetry with regard to the manifestation of manic and depressive emotional traits in FLE and MTLE, respectively. Our results are mainly discussed within the frame of their contribution in localizing and to a lesser extent in lateralizing seizures foci in epilepsy surgery candidates. We suggest that this is of great importance in the context of preoperative monitoring of epilepsy surgery, especially when neuropsychologists are called upon to provide anatomical information in defining the functional deficit zone.

T01. Role of hypothalamic hamartoma in non-gelastic seizures: An exploration of the brain network

Patients having a hypothalamic hamartoma frequently present epileptic attacks of laughter, and they later experience multiple additional seizure types. Because of these types of seizures, hypothalamic hamartomas are considered to be a type of pharmacoresistant epilepsy. Gelastic seizures are associated with hypothalamic hamartomas, but the relationship between hypothalamic hamartomas and other non-gelastic seizures is unknown. Deep electrodes were placed in the hypothalamic hamartoma (anterior, superior, medial aspect), bilateral anterior nuclei of the thalamus, bilateral cingulate gyri, bilateral hippocampi, and bilateral hippocampal sides of the hypothalamic hamartoma under stereotactic guidance. Clinical manifestations and electroencephalograms (EEG) were collected during intermittent and acute stages. The seizure generator zone was located. Seizures in adult patients with hypothalamic hamartomas usually consist of the following types: generalized tonic-clonic seizures; partial tonic seizures; excessive body movements (hip swing and automotor seizures); and evolving seizures (generalized tonic-clonic seizures evolving to excessive body movements or excessive body movements evolving to brief generalized tonic-clonic seizures). The clinical manifestations usually occur later than the discharges in the hypothalamic hamartoma. Seizures originating from the anterior, superior, medial aspect of the hypothalamic hamartoma propagate first to the anterior nucleus of the thalamus. Symptoms are generated in the bilateral cingulate gyri and prefrontal cortex, especially in the cingulate gyri. As the seizures continue to propagate, ictal onset is triggered in the hippocampus, which leads to generalized tonic-clonic seizures. The amygdala and hippocampus are the regions of single cell discharges; no apparent discharges were observed in the amygdala-hippocampal side of the hypothalamic hamartoma. Through stereotactic electrode implantation, we confirmed that the conducting pathway of seizures from a hypothalamic hamartoma is the hypothalamus-anterior nucleus of the thalamus-cingulate gyrus-prefrontal cortex. Ictal symptoms disappeared post-operatively, which further proved the “running down” phenomenon. After removing the persistent effect of the hypothalamic hamartoma on the frontal (mammillary body-mammillothalamic fasciculus- anterior nucleus of the thalamus-cingulate gyrus-frontal lobe) and temporal lobes (connections between the hypothalamus and amygdala or the fornix-medial temporal lobe), epileptiform discharges in the temporal and frontal lobes improved. This finding indicated that neocortical temporal lobe epilepsy originates from the hypothalamic hamartoma. These results provide guidance for the treatment of seizures in patients with hamartomas and contribute to an understanding of the brain network.

Hippocampography Guides Consistent Mesial Resections in Neocortical Temporal Lobe Epilepsy.

Background. The optimal surgery in lesional neocortical temporal lobe epilepsy is unknown. Hippocampal electrocorticography maximizes seizure freedom by identifying normal-appearing epileptogenic tissue for resection and minimizes neuropsychological deficit by limiting resection to demonstrably epileptogenic tissue. We examined whether standardized hippocampal electrocorticography (hippocampography) guides resection for more consistent hippocampectomy than unguided resection in conventional electrocorticography focused on the lesion. Methods. Retrospective chart reviews any kind of electrocorticography (including hippocampography) as part of combined lesionectomy, anterolateral temporal lobectomy, and hippocampectomy over 8 years . Patients were divided into mesial (i.e., hippocampography) and lateral electrocorticography groups. Primary outcome was deviation from mean hippocampectomy length. Results. Of 26 patients, fourteen underwent hippocampography-guided mesial temporal resection. Hippocampography was associated with 2.6 times more consistent resection. The range of hippocampal resection was 0.7 cm in the mesial group and 1.8 cm in the lateral group (p = 0.01). 86% of mesial group versus 42% of lateral group patients achieved seizure freedom (p = 0.02). Conclusions. By rationally tailoring excision to demonstrably epileptogenic tissue, hippocampography significantly reduces resection variability for more consistent hippocampectomy than unguided resection in conventional electrocorticography. More consistent hippocampal resection may avoid overresection, which poses greater neuropsychological risk, and underresection, which jeopardizes postoperative seizure freedom.

ID 358 – Hypermotor seizures in patients with temporal lobe epilepsy

Purpose Hypermotor seizures are considered to be characteristic of frontal lobe epilepsy, with only rare occurrence in temporal lobe epilepsy (TLE). The objective of this study was to determine the features of TLE with hypermotor seizures. Methods Patients with medically refractory TLE, who underwent video-EEG monitoring between 2006 and 2015 at our epilepsy center were included the study. We retrospectively identified patients investigated whom hyperkinetic manifestations were proved to be linked to initial temporal lobe involvement. Results We identified 6 patients with hypermotor seizures from our database. We analyzed all recorded seizures for detailed semiology and ictal EEG features. MRI and FDG-PET imaging were performed. Two patients with hypermotor seizures had implanted frontal and temporal subdural electrodes demonstrating temporal initiation and frontal spread before hypermotor behavior. Ictal EEG showed that onset of seizures were neocortical temporal lobe origin in 4 patients. Discussion Seizures originating in the temporal lobe must be recognized as an important cause of hyperkinetic seizures. Hypermotor seizures are more common in patients with neocortical temporal lobe epilepsy than with mesial temporal lobe epilepsy. Our findings are important to recognize of TLE with hypermotor seizures and help making decision for epilepsy surgery.

Sleep affects cortical source modularity in temporal lobe epilepsy: A high-density EEG study

ObjectiveInterictal epileptiform discharges (IEDs) constitute a perturbation of ongoing cerebral rhythms, usually more frequent during sleep. The aim of the study was to determine whether sleep influences the spread of IEDs over the scalp and whether their distribution depends on vigilance-related modifications in cortical interactions. MethodsWake and sleep 256-channel electroencephalography (EEG) data were recorded in 12 subjects with right temporal lobe epilepsy (TLE) differentiated by whether they had mesial or neocortical TLE. Spikes were selected during wake and sleep. The averaged waking signal was subtracted from the sleep signal and projected on a bidimensional scalp map; sleep and wake spike distributions were compared by using a t-test. The superimposed signal of sleep and wake traces was obtained; the rising phase of the spike, the peak, and the deflections following the spike were identified, and their cortical generator was calculated using low-resolution brain electromagnetic tomography (LORETA) for each group. ResultsA mean of 21 IEDs in wake and 39 in sleep per subject were selected. As compared to wake, a larger IED scalp projection was detected during sleep in both mesial and neocortical TLE (p<0.05). A series of EEG deflections followed the spike, the cortical sources of which displayed alternating activations of different cortical areas in wake, substituted by isolated, stationary activations in sleep in mesial TLE and a silencing in neocortical TLE. ConclusionDuring sleep, the IED scalp region increases, while cortical interaction decreases. SignificanceThe interaction of cortical modules in sleep and wake in TLE may influence the appearance of IEDs on scalp EEG; in addition, IEDs could be proxies for cerebral oscillation perturbation.

4. Familial generalized seizures due to LGI1 mutation: Importance of family history for genetic testing

Background It is well known that patients with temporal lobe epilepsy may present with generalized seizures, and the temporal localization depends on further investigation. We present a family with five individuals in three generations where the clinical pattern consisted largely of generalized seizures, but who were then shown to have epilepsy due to an LGI1 mutation. We wish to discuss the clinical and EEG findings in these patients, and to compare these with families with autosomal dominant partial epilepsy with auditory features (ADPEAF) or familial lateral temporal lobe epilepsy (FLTLE) reported in the literature. Family report The proband is a 46-year-old female college graduate who had normal development and no history of head trauma, central nervous system infection or febrile seizures. She had four nocturnal generalized tonic-clonic seizures (GTCS), all occurred around 5–6 am, the first one at age 19years. Diphenylhydantoin was prescribed and later replaced by carbamazepine CR. She has been seizure free since adequate compliance with treatment. Her first EEG performed at 19 years showed an excess of slow waves at 2–4Hz over both posterior head regions without epileptic activity. Her second EEG at 22years showed spikes and slow spike waves alternating over both temporal regions, mostly during drowsiness, and increased during hyperventilation. During intermittent photic stimulation, a photomyoclonic response appeared. Her 40-year-old sister had her first GTCS at 12years which was generalized from the onset. All but one of her subsequent attacks occurred during sleep. Before the only seizure that occurred while awake, she felt numbness of her whole body and heard a whooshing sound suggestive of neocortical temporal lobe involvement. The third sister is 52years old; she had her first GTCS at 19years. A year prior to this, she had transient symptoms of a tingling sensation associated with a whooshing noise. She later had other generalized attacks preceded by this aura. A diagnosis of neocortical or lateral temporal lobe epilepsy, possibly ADPEAF or FLTLE, was suggested. Although the proband only had nocturnal GTCS, LGI1 sequencing was performed on the basis of the family history. A c.611delC mutation leading to a frameshift and premature termination of the protein was identified. Discussion Generalized nocturnal and diurnal seizures associated with interictal generalized spike-wave activity occurring in a family with ADPEAF is unusual. They may represent secondarily generalized seizures or primary generalized seizures or both. In addition, photosensitivity in the proband is unusual as well. Among the reported patients with LGI1 mutation, there are several who have had GTCS and interictal generalized spike-wave and/or polyspike-wave discharges [Ottman et al., 2004]. This family further illustrates that patients with ADPEAF or FLTLE may present with generalized seizures and generalized spike and wave epileptic discharges. Intensive monitoring and attention to aura with auditory features should lead to accurate diagnosis of this genetically determined epileptic syndrome. This report points to the importance of detailed family history to help orient the diagnosis by genetic testing.

Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis

Metabotropic glutamate receptor type 5 (mGluR5) upregulation in temporal lobe epilepsy (TLE) and the correlation of its expression with features of hippocampal sclerosis (HS) remains unclear. Here we characterized mGluR5 immunoreactivity in hippocampus, entorhinal cortex (EC), and subiculum of TLE specimens with confirmed HS, with neocortical TLE (non-HS) and necropsy controls. We correlated mGluR5 immunoreactivity with neuronal density, mossy fiber sprouting, astrogliosis (GFAP), and dendritic alterations (MAP2). TLE specimens showed increased mGluR5 expression, which was most pronounced in the EC, subiculum, CA2, and dentate gyrus outer molecular layer. Increased mGluR5 expression was seen in hippocampal head and body segments and was independent of neuronal density, astrogliosis, or dendritic alterations. Positive correlation between mGluR5 expression with mossy fiber sprouting and with MAP2 in CA3 and CA1 was found only in HS specimens. Negative correlation between mGluR5 expression with seizure frequency and epilepsy duration was found only in non-HS cases. Specimens from HS patients without previous history of febrile seizure (FS) showed higher mGluR5 and MAP2 expression in CA2. Our study suggests that mGluR5 upregulation is part of a repertoire of post-synaptic adaptations that might control overexcitation and excessive glutamate release rather than a dysfunction that leads to seizure facilitation. That would explain why non-HS cases, on which seizures are likely to originate outside the hippocampal formation, also exhibit upregulated mGluR5. On the other hand, lower mGluR5 expression was related to increased seizure frequency. In addition to its role in hyperexcitability, mGluR5 upregulation could play a role in counterbalance mechanisms along the hyperexcitable circuitry uniquely altered in sclerotic hippocampal formation. Inefficient post-synaptic compensatory morphological (dendritic branching) and glutamatergic (mGluR5 expression) mechanisms in CA2 subfield could potentially underlie the association of FS with HS and TLE. © 2013 Wiley Periodicals, Inc.

Sleep modulation of epileptic activity in mesial and neocortical temporal lobe epilepsy: A study with depth and subdural electrodes

This study characterizes the spatial–temporal distribution of epileptic activity in mesial and neocortical temporal lobe epilepsy (TLE) assessed by subdural and depth electrodes during sleep. We determined in 13 patients the frequency, lateralization, and localization of interictal epileptic discharges (IEDs). As compared to the waking state, IEDs increased in light sleep (196%, p<0.05) and in deep sleep (601%, p<0.05) but did not change significantly in REM sleep (−8.33%, p=0.94). From 11 patients with unilateral TLE, in all cases, IEDs lateralized to the seizure onset side during REM sleep and the waking state. In mesial TLE, IEDs tended to shift in an anterior–posterior axis and remained always localized in the amygdalo–hippocampal complex. By contrast, in neocortical TLE, the maximal activity moved in a mesial–lateral axis between neocortical and mesial structures. Twenty-six seizures were registered in 7 patients, 22 of which occurred in light sleep and 4 in wakefulness, but none occurred in deep or REM sleep.

Update on Temporal Lobe Epilepsy

Update on Temporal Lobe Epilepsy