Intracerebral Correlates of Scalp EEG Ictal Discharges Based on Simultaneous Stereo-EEG Recordings.

BACKGROUND AND OBJECTIVES: It remains unknown to what extent ictal scalp EEG can accurately predict the localization of the intracerebral seizure onset in presurgical evaluation of drug-resistant epilepsies. In this study, we aimed to define homogeneous ictal scalp EEG profiles (based on their first ictal abnormality) and assess their localizing value using simultaneously recorded scalp EEG and stereo-EEG. METHODS: We retrospectively included consecutive patients with drug-resistant focal epilepsy who had simultaneous stereo-EEG and scalp EEG recordings of at least 1 seizure in the epileptology unit in Nancy, France. We analyzed 1 seizure per patient and used hierarchical cluster analysis to group similar seizure profiles on scalp EEG and then performed a descriptive analysis of their intracerebral correlates. RESULTS: We enrolled 129 patients in this study. The hierarchical cluster analysis showed 6 profiles on scalp EEG first modification. None were specific to a single intracerebral localization. The "normal EEG" and "blurred EEG" clusters (early muscle artifacts) comprised only 5 patients each and corresponded to no preferential intracerebral localization. The "temporal discharge" cluster (n = 46) was characterized by theta or delta discharges on ipsilateral anterior temporal scalp electrodes and corresponded to a preferential mesial temporal intracerebral localization. The "posterior discharge" cluster (n = 42) was characterized by posterior ipsilateral or contralateral rhythmic alpha discharges or slow waves on scalp and corresponded to a preferential temporal localization. However, this profile was the statistically most frequent scalp EEG correlate of occipital and parietal seizures. The "diffuse suppression" cluster (n = 9) was characterized by a bilateral and diffuse background activity suppression on scalp and corresponded to mesial, and particularly insulo-opercular, localization. Finally, the "frontal discharge" cluster (n = 22) was characterized by bilateral frontal rhythmic fast activity or preictal spike on scalp and corresponded to preferential ventrodorsal frontal intracerebral localizations. DISCUSSION: The hierarchical cluster analysis identified 6 seizure profiles regarding the first abnormality on scalp EEG. None of them were specific of a single intracerebral localization. Nevertheless, the strong relationships between the "temporal," "frontal," "diffuse suppression," and "posterior" profiles and intracerebral discharge localizations may contribute to hierarchize hypotheses derived from ictal scalp EEG analysis regarding intracerebral seizure onset.

Cell to network computational model of the epileptic human hippocampus suggests specific roles of network and channel dysfunctions in the ictal and interictal oscillations.

The mechanisms underlying the generation of hippocampal epileptic seizures and interictal events and their interactions with the sleep-wake cycle are not yet fully understood. Indeed, medial temporal lobe epilepsy is associated with hippocampal abnormalities both at the neuronal (channelopathies, impaired potassium and chloride dynamics) and network level (neuronal and axonal loss, mossy fiber sprouting), with more frequent seizures during wakefulness compared with slow-wave sleep. In this article, starting from our previous computational modeling work of the hippocampal formation based on realistic topology and synaptic connectivity, we study the role of micro- and mesoscale pathological conditions of the epileptic hippocampus in the generation and maintenance of seizure-like theta and interictal oscillations. We show, through the simulations of hippocampal activity during slow-wave sleep and wakefulness that: (i) both mossy fiber sprouting and sclerosis account for seizure-like theta activity, (ii) but they have antagonist effects (seizure-like activity occurrence increases with sprouting but decreases with sclerosis), (iii) though impaired potassium and chloride dynamics have little influence on the generation of seizure-like activity, they do play a role on the generation of interictal patterns, and (iv) seizure-like activity and fast ripples are more likely to occur during wakefulness and interictal spikes during sleep.

Naming impairments evoked by focal cortical electrical stimulation in the ventral temporal cortex correlate with increased functional connectivity.

BACKGROUND: High-frequency cortical electrical stimulations (HF-CES) are the gold standard for presurgical functional mapping. In the dominant ventral temporal cortex (VTC) HF-CES can elicit transient naming impairment (eloquent sites), defining a basal temporal language area (BTLA). OBJECTIVE: Whether naming impairments induced by HF-CES within the VTC are related to a specific pattern of connectivity of the BTLA within the temporal lobe remains unknown. We addressed this issue by comparing the connectivity of eloquent and non-eloquent sites from the VTC using cortico-cortical evoked potentials (CCEP). METHODS: Low frequency cortical electrical stimulations (LF-CES) were used to evoke CCEP in nine individual brains explored with Stereo-Electroencephalography. We compared the connectivity of eloquent versus non eloquent sites within the VTC using Pearson's correlation matrix. RESULTS: Overall, within the VTC, eloquent sites were associated with increased functional connectivity compared to non-eloquent sites. Among the VTC structures, this pattern holds true for the inferior temporal gyrus and the parahippocampal gyrus while the fusiform gyrus specifically showed a high connectivity in both non eloquent and eloquent sites. CONCLUSIONS: Our findings suggest that the cognitive effects of focal HF-CES are related to the functional connectivity properties of the stimulated sites, and therefore to the disturbance of a wide cortical network. They further suggest that functional specialization of a cortical region emerges from its specific pattern of functional connectivity. Cortical electrical stimulation functional mapping protocols including LF coupled to HF-CES could provide valuable data characterizing both local and distant functional architecture.

Anticipatory anxiety of seizures is associated with ictal emotional distress and amygdala onset seizures.

OBJECTIVE: Anxiety disorders are a frequent psychiatric condition in patients with epilepsy. Anticipatory anxiety of seizures (AAS) is described as a daily persistent fear or excessive worry of having a seizure. AAS seems to be related to "subjective ictal anxiety" reported by patients. The current study aimed to assess the association between objective ictal features and the presence of AAS. METHODS: Ninety-one patients with drug-resistant focal epilepsy underwent a standardized psychiatric assessment, specific for epilepsy, and presurgical long-term video-electroencephalography (EEG) or stereo-EEG (SEEG). We compared seizure semiology and epilepsy features of patients with AAS (n = 41) to those of patients without AAS (n = 50). We analyzed emotional and motor behavior ictal signs as well as ictal consciousness. We further assessed amygdala ictal involvement in seizures recorded with SEEG (n = 28). RESULTS: AAS was significantly associated with the presence of ictal emotional distress; negative emotional behavior (p < .01) and negative emotion were explicitly reported to the examiner during recording (p = .015), regardless of the ictal level of consciousness. Among the patients recorded with SEEG, we found a significant involvement of amygdala within the seizure onset zone (p < .01) for patients with AAS. SIGNIFICANCE: Higher risk of developing AAS is associated with seizures expressing negative emotional symptoms, independently of ictal consciousness level. Persistent interictal fear of seizures might be viewed as the consequence of a reinforcement of the emotional networks secondary to amygdala involvement in seizures of temporal origin. Physicians should screen for AAS not only to assess the impact of epilepsy on daily life, but also as an interictal biomarker of ictal semiology and emotional network involvement at seizure onset.

Postictal psychosis, a cause of secondary affective psychosis: A clinical description study of 77 patients.

OBJECTIVE: Postictal psychosis (PIP) is a severe complication occurring at least in 2% of patients with epilepsy. Since the 19th century, psychiatrists have reported the specificity of PIP presentation, but descriptions did not clearly distinguish PIP from after-seizure delirium. This study aimed to provide a precise description of psychiatric signs occurring during PIP, and improve recognition of PIP. METHODS: We performed a review of clinical descriptions available in literature (48 patients), that we gathered with a retrospective multicentric case series of patients from three French epilepsy units (29 patients). For each patient, we collected retrospectively the psychiatric signs, and epilepsy features. RESULTS: We found a high prevalence of persecutory (67.5%) and religious (55.8%) delusions, with almost systematic hallucinations (83.1%) and frequent mood disturbances (76.6%), especially euphoria. Severe consequences were not negligible (other-directed assault in 20.8%, self-directed in 13.0%). The type of delusion was associated with mood symptoms (p = 0.017). Episode onset was mainly sudden/rapid (90.9%), its duration was mostly between one and 14 days (64.9%) and the response to antipsychotic medication was good. Disorder was recurrent in more than a half of the sample (57.1% of patients with at least 2 episodes). CONCLUSION: Considering our findings, PIP resembles more an affective psychosis, than a purely psychotic disorder. The presence of affective signs differentiates PIP from other psychotic comorbidities in epilepsy. Additionally, resemblance between PIP and psychotic manic episode might help to discuss links between epilepsy and bipolar disorder.

Epilepsy in Early Onset Alzheimer's Disease.

BACKGROUND: Epilepsy seems to be an important comorbidity in patients with early onset Alzheimer's disease (EOAD). Currently, seizures are still underestimated in this population. However, seizures may interact with AD evolution with possible acceleration of cognitive decline. OBJECTIVE: To better define the epileptic disorders observed in patients with EOAD. METHODS: All patients diagnosed as EOAD in our hospital between 2013 and 2019 with positive CSF biomarkers for AD were selected. The usual follow-up was extended with a 3-h EEG and a consultation with an epilepsy expert. Information on epilepsy and AD were collected and analyzed. RESULTS: Among the 25 included patients, 10 (40%) were classified as epileptic. Seizure types were tonic-clonic (25%), typical temporal seizures (25%), myoclonus (25%), focal extra-temporal seizures (8%), and other seizure types (17%). AD-E patients had a significant lower MMSE (15.3±8.4 AD-E versus 22.1±5.1 AD-NE, p = 0.036) and a lower autonomy (IADL 4.1±2.7 AD-E versus 6.4±1.9 AD-NE, p = 0.046) at AD diagnosis with comparable ages between AD-E and AD-NE. Epileptic patients seemed to present a faster cognitive decline ([ΔMMSE per year 1.7±1.3 AD-E versus 0.9±1.4 AD-NE; p = 0.09). All patients with severe cognitive impairment (MMSE ≤ 10) had an epileptic comorbidity. CONCLUSION: Epilepsy is a frequent comorbidity in EOAD patients, with a percentage of 40%in our study. This comorbidity may be associated with a severe form of EOAD. The role of epilepsy in the acceleration of cognitive decline and the positive impact of antiepileptic drugs on cognition need further research.

Language Mapping Using Stereo Electroencephalography: A Review and Expert Opinion.

Stereo-electroencephalography (sEEG) is a method that uses stereotactically implanted depth electrodes for extra-operative mapping of epileptogenic and functional networks. sEEG derived functional mapping is achieved using electrical cortical stimulations (ECS) that are currently the gold standard for delineating eloquent cortex. As this stands true especially for primary cortices (e.g., visual, sensitive, motor, etc.), ECS applied to higher order brain areas determine more subtle behavioral responses. While anterior and posterior language areas in the dorsal language stream seem to share characteristics with primary cortices, basal temporal language area (BTLA) in the ventral temporal cortex (VTC) behaves as a highly associative cortex. After a short introduction and considerations about methodological aspects of ECS using sEEG, we review the sEEG language mapping literature in this perspective. We first establish the validity of this technique to map indispensable language cortices in the dorsal language stream. Second, we highlight the contrast between the growing empirical ECS experience and the lack of understanding regarding the fundamental mechanisms underlying ECS behavioral effects, especially concerning the dispensable language cortex in the VTC. Evidences for considering network architecture as determinant for ECS behavioral response complexities are discussed. Further, we address the importance of designing new research in network organization of language as this could enhance ECS ability to map interindividual variability, pathology driven reorganization, and ultimately identify network resilience markers in order to better predict post-operative language deficit. Finally, based on a whole body of available studies, we believe there is strong evidence to consider sEEG as a valid, safe and reliable method for defining eloquent language cortices although there have been no proper comparisons between surgical resections with or without extra-operative or intra-operative language mapping.

Stereoelectroencephalographic language mapping of the basal temporal cortex predicts postoperative naming outcome.

OBJECTIVE: In drug-resistant temporal lobe epilepsy (TLE) patients, the authors evaluated early and late outcomes for decline in visual object naming after dominant temporal lobe resection (TLR) according to the resection status of the basal temporal language area (BTLA) identified by cortical stimulation during stereoelectroencephalography (SEEG). METHODS: Twenty patients who underwent SEEG for drug-resistant TLE met the inclusion criteria. During language mapping, a site was considered positive when stimulation of two contiguous contacts elicited at least one naming impairment during two remote sessions. After TLR ipsilateral to their BTLA, patients were classified as BTLA+ when at least one positive language site was resected and as BTLA- when all positive language sites were preserved. Outcomes in naming and verbal fluency tests were assessed using pre- and postoperative (means of 7 and 25 months after surgery) scores at the group level and reliable change indices (RCIs) for clinically meaningful changes at the individual level. RESULTS: BTLA+ patients (n = 7) had significantly worse naming scores than BTLA- patients (n = 13) within 1 year after surgery but not at the long-term evaluation. No difference in verbal fluency tests was observed. When RCIs were used, 5 of 18 patients (28%) had naming decline within 1 year postoperatively (corresponding to 57% of BTLA+ and 9% of BTLA- patients). A significant correlation was found between BTLA resection and naming decline. CONCLUSIONS: BTLA resection is associated with a specific and early naming decline. Even if this decline is transient, naming scores in BTLA+ patients tend to remain lower compared to their baseline. SEEG mapping helps to predict postoperative language outcome after dominant TLR.