No major effect of dopamine receptor 1/5 antagonist SCH-23390 on epileptic activity in the Tg2576 mouse model of amyloidosis.

The excitation-inhibition imbalance manifesting as epileptic activities in Alzheimer's disease is gaining more and more attention, and several potentially involved cellular and molecular pathways are currently under investigation. Based on in vitro studies, dopamine D1-type receptors in the anterior cingulate cortex and the hippocampus have been proposed to participate in this peculiar co-morbidity in mouse models of amyloidosis. Here, we tested the implication of dopaminergic transmission in vivo in the Tg2576 mouse model of Alzheimer's disease by monitoring epileptic activities via intracranial EEG before and after treatment with dopamine antagonists. Our results show that neither the D1-like dopamine receptor antagonist SCH23390 nor the D2-like dopamine receptor antagonist haloperidol reduces the frequency of epileptic activities. While requiring further investigation, our results indicate that on a systemic level, dopamine receptors are not significantly contributing to epilepsy observed in vivo in this mouse model of Alzheimer's disease.

Local neuronal excitation and global inhibition during epileptic fast ripples in humans.

Understanding the neuronal basis of epileptic activity is a major challenge in neurology. Cellular integration into larger scale networks is all the more challenging. In the local field potential, interictal epileptic discharges can be associated with fast ripples (200-600 Hz), which are a promising marker of the epileptogenic zone. Yet, how neuronal populations in the epileptogenic zone and in healthy tissue are affected by fast ripples remain unclear. Here, we used a novel 'hybrid' macro-micro depth electrode in nine drug-resistant epileptic patients, combining classic depth recording of local field potentials (macro-contacts) and two or three tetrodes (four micro-wires bundled together) enabling up to 15 neurons in local circuits to be simultaneously recorded. We characterized neuronal responses (190 single units) with the timing of fast ripples (2233 fast ripples) on the same hybrid and other electrodes that target other brain regions. Micro-wire recordings reveal signals that are not visible on macro-contacts. While fast ripples detected on the closest macro-contact to the tetrodes were always associated with fast ripples on the tetrodes, 82% of fast ripples detected on tetrodes were associated with detectable fast ripples on the nearest macro-contact. Moreover, neuronal recordings were taken in and outside the epileptogenic zone of implanted epileptic subjects and they revealed an interlay of excitation and inhibition across anatomical scales. While fast ripples were associated with increased neuronal activity in very local circuits only, they were followed by inhibition in large-scale networks (beyond the epileptogenic zone, even in healthy cortex). Neuronal responses to fast ripples were homogeneous in local networks but differed across brain areas. Similarly, post-fast ripple inhibition varied across recording locations and subjects and was shorter than typical inter-fast ripple intervals, suggesting that this inhibition is a fundamental refractory process for the networks. These findings demonstrate that fast ripples engage local and global networks, including healthy tissue, and point to network features that pave the way for new diagnostic and therapeutic strategies. They also reveal how even localized pathological brain dynamics can affect a broad range of cognitive functions.

[Evaluation of the relevance of the pharmaceutical educational interview on the knowledge and satisfaction of patients who received a vagus nerve neurostimulator implantation]. / Évaluation de la pertinence de l'entretien pharmaceutique éducatif sur les connaissances et la satisfaction de patients ayant bénéficié d'une implantation d'un neurostimulateur du nerf vague.

INTRODUCTION: Vagal neurostimulation (VNS) medical devices (MDs) are used to treat drug-resistant epilepsy. Using a magnet, the patient can activate on the stimulations in order to stop a seizure or interrupt the adverse effects (AEs) of the device. The objective is to evaluate the improvement of the patients' knowledge about the VNS following a pharmaceutical educational interview (PEI) as well as their satisfaction. MATERIALS AND METHODS: The pharmaceutical educational interview regarding drugs and DMs was performed by the clinical pharmacist at the patient's bed after VNS implantation. A questionnaire about VNS devices (operation, adverse effects, recommendations) and assessing knowledge was submitted to patients before and after the PEI. Satisfaction was assessed by the Likert scale. RESULTS: From March 2020 to August 2021, 18 implanted patients were included in the study. In 78% of cases (14/18), the total number of good responses after PEI increased. The mean good response was significantly increased from 16.11/25 (64%) before PEI to 22.33/25 (89%) after PEI (P-value<0.01). The maximum satisfaction score (4/4) was given in 71% of the items. DISCUSSION-CONCLUSION: The results support the relevance of PEI. Patients feel a need for information and consider the interview useful. An improvement in knowledge was observed, which allows us to hope for an optimization of the effectiveness of the device, in particular, a reduction in seizures and AE. This study shows the feasibility and the interest of the development of clinical pharmacy applied to medical devices in complementarity with the expertise on drugs.

Large-scale network dynamics underlying the first few hundred milliseconds after stimulus presentation: An investigation of visual recognition memory using iEEG.

Recognition memory is the ability to recognize previously encountered objects. Even this relatively simple, yet extremely fast, ability requires the coordinated activity of large-scale brain networks. However, little is known about the sub-second dynamics of these networks. The majority of current studies into large-scale network dynamics is primarily based on imaging techniques suffering from either poor temporal or spatial resolution. We investigated the dynamics of large-scale functional brain networks underlying recognition memory at the millisecond scale. Specifically, we analyzed dynamic effective connectivity from intracranial electroencephalography while epileptic subjects (n = 18) performed a fast visual recognition memory task. Our data-driven investigation using Granger causality and the analysis of communities with the Louvain algorithm spotlighted a dynamic interplay of two large-scale networks associated with successful recognition. The first network involved the right visual ventral stream and bilateral frontal regions. It was characterized by early, predominantly bottom-up information flow peaking at 115 ms. It was followed by the involvement of another network with predominantly top-down connectivity peaking at 220 ms, mainly in the left anterior hemisphere. The transition between these two networks was associated with changes in network topology, evolving from a more segregated to a more integrated state. These results highlight that distinct large-scale brain networks involved in visual recognition memory unfold early and quickly, within the first 300 ms after stimulus onset. Our study extends the current understanding of the rapid network changes during rapid cognitive processes.

Interactions between antiseizure medications and contraception: A study about the knowledge of patients and their specialist physicians.

Planning pregnancy is very important for women with epilepsy (WWE), because of the potential teratogenic effects and neurodevelopmental disorders of different antiseizure medications (ASMs). Nevertheless, contraception in WWE can be challenging due to the existence of drug interactions between ASMs and hormonal contraception. The aim of this study was to assess women's knowledge of potential interactions between their ASMs and contraceptive options. The second objective was to assess neurologist's knowledge of the potential interactions between ASMs and contraceptive methods. An anonymous online survey was proposed to reproductive-age WWE during consultation with their neurologist. Another online survey was proposed to neurologists. These surveys were performed through a French regional medical network. A total of 79 patients agreed to respond to the survey. Forty-nine women used lamotrigine alone or in combination, 15 used an enzyme-inducing ASM alone or in combination, 13 used non-enzyme-inducing ASM and 2 used both lamotrigine and an enzyme-inducing ASM. Half of the WWE had mistaken beliefs about interactions between their ASM and contraception. Among them, 35% of the women treated with an enzyme-inducing ASM were unaware of a potential decreased efficacy of hormonal contraception. Moreover, 51% of the women who were taking lamotrigine did not know that combined hormonal contraception might decrease the efficacy of their ASM. On the other hand, 64.5% of WWE without an enzyme-inducing ASM wrongly thought that their ASM can decrease their hormonal contraceptive efficacy. A total of 20 neurologists answered the online survey. It revealed specific gaps concerning interactions between ASM and contraceptives; in fact, 35% of answers concerning the identification of specific enzyme-inducing ASMs were wrong. This study therefore highlights the need for educational efforts for both WWE and their physicians regarding drug interactions between ASMs and hormonal contraceptives.

Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy.

OBJECTIVE: To assess the relation between coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy. METHODS: Cross-sectional analysis of data collected in the SAVE study, which included patients with drug-resistant focal epilepsy during long-term EEG monitoring. Patients in whom both coffee consumption and data about seizure frequency, including focal to bilateral tonic-clonic seizures (FBTCS), were available were selected. Coffee consumption was collected using a standardized self-report questionnaire and classified into four groups: none, rare (from less than 1 cup/week to up 3 cups/week), moderate (from 4 cups/week to 3 cups/day), and high (more than 4 cups/day). RESULTS: Six hundred and nineteen patients were included. There was no relation between coffee consumption and total seizure frequency (p = 0.902). In contrast, the number of FBTCS reported over the past year was significantly associated with usual coffee consumption (p = 0.029). Specifically, number of FBCTS in patients who reported moderate coffee consumption was lower than in others. In comparison with patients with moderate coffee consumption, the odds ratio (95%CI) for reporting at least 1 FBTCS per year was 1.6 (1.03-2.49) in patients who never take coffee, 1.62 (1.02-2.57) in those with rare consumption and 2.05 (1.24-3.4) in those with high consumption. Multiple ordinal logistic regression showed a trend toward an association between coffee consumption and number of FBTCS (p = 0.08). CONCLUSIONS AND RELEVANCE: Our data suggest that effect of coffee consumption on seizures might depend on dose with potential benefits on FBTCS frequency at moderate doses. These results will have to be confirmed by prospective studies.

A Fast Visual Recognition Memory System in Humans Identified Using Intracerebral ERP.

One key item of information retrieved when surveying our visual world is whether or not objects are familiar. However, there is no consensus on the respective roles of medial temporal lobe structures, particularly the perirhinal cortex (PRC) and hippocampus. We considered whether the PRC could support a fast recognition memory system independently from the hippocampus. We recorded the intracerebral electroencephalograph activity of epileptic patients while they were performing a fast visual recognition memory task, constraining them to use their quickest strategy. We performed event-related potential (ERP) and classification analyses. The PRC was, by far, the earliest region involved in recognition memory. This activity occurred before the first behavioral responses and was found to be related to reaction times, unlike the hippocampus. Single-trial analyses showed that decoding power was equivalent in the PRC and hippocampus but occurred much earlier in the PRC. A critical finding was that recognition memory-related activity occurred in different frontal and parietal regions, including the supplementary motor area, before the hippocampus. These results, based on ERP analyses, suggest that the human brain is equipped with a fast recognition memory system, which may bypass the hippocampus and in which the PRC plays a critical role.

Stereoelectroencephalography (SEEG) and epilepsy surgery in posttraumatic epilepsy: A multicenter retrospective study.

PURPOSE: Posttraumatic epilepsy (PTE) is a common cause of drug-resistant epilepsy, especially in young adults. Nevertheless, such patients are not common candidates for intracranial presurgical evaluation. We investigated the role of stereoelectroencephalography (SEEG) in defining epileptogenicity and surgical strategy in patients with PTE. METHODS: We analyzed ictal SEEG recordings from 18 patients. We determined the seizure onset zone (SOZ) by quantifying the epileptogenicity of the sampled structures, using the "epileptogenicity index" (EI). We also identified seizure onset patterns (SOPs) through visual and frequency analysis. Postsurgical outcome was assessed by Engel's classification. RESULTS: The SOZ in PTE was most often located in temporal lobes, followed by frontal lobes. The SOZ was network-organized in the majority of the cases. Half of the SOP did not contain fast discharges. Half of the recordings showed SOZ that were less extensive than the posttraumatic lesions seen on brain magnetic resonance imaging (MRI). All but one operated patient benefited from tailored cortectomy. Only 3 patients were contraindicated for surgical resection due to bilateral epileptogenicity. The overall surgical outcome was good in majority of patients (67% Engel I). CONCLUSION: Despite the potential risk of bilateral or multifocal epilepsy, patients with PTE may benefit from presurgical assessment in well-selected cases. In this context, SEEG allows guidance of tailored resections adapted to the SOZ.

Probabilistic functional tractography of the human cortex revisited.

In patients with pharmaco-resistant focal epilepsies investigated with intracranial electroencephalography (iEEG), direct electrical stimulations of a cortical region induce cortico-cortical evoked potentials (CCEP) in distant cerebral cortex, which properties can be used to infer large scale brain connectivity. In 2013, we proposed a new probabilistic functional tractography methodology to study human brain connectivity. We have now been revisiting this method in the F-TRACT project (f-tract.eu) by developing a large multicenter CCEP database of several thousand stimulation runs performed in several hundred patients, and associated processing tools to create a probabilistic atlas of human cortico-cortical connections. Here, we wish to present a snapshot of the methods and data of F-TRACT using a pool of 213 epilepsy patients, all studied by stereo-encephalography with intracerebral depth electrodes. The CCEPs were processed using an automated pipeline with the following consecutive steps: detection of each stimulation run from stimulation artifacts in raw intracranial EEG (iEEG) files, bad channels detection with a machine learning approach, model-based stimulation artifact correction, robust averaging over stimulation pulses. Effective connectivity between the stimulated and recording areas is then inferred from the properties of the first CCEP component, i.e. onset and peak latency, amplitude, duration and integral of the significant part. Finally, group statistics of CCEP features are implemented for each brain parcel explored by iEEG electrodes. The localization (coordinates, white/gray matter relative positioning) of electrode contacts were obtained from imaging data (anatomical MRI or CT scans before and after electrodes implantation). The iEEG contacts were repositioned in different brain parcellations from the segmentation of patients' anatomical MRI or from templates in the MNI coordinate system. The F-TRACT database using the first pool of 213 patients provided connectivity probability values for 95% of possible intrahemispheric and 56% of interhemispheric connections and CCEP features for 78% of intrahemisheric and 14% of interhemispheric connections. In this report, we show some examples of anatomo-functional connectivity matrices, and associated directional maps. We also indicate how CCEP features, especially latencies, are related to spatial distances, and allow estimating the velocity distribution of neuronal signals at a large scale. Finally, we describe the impact on the estimated connectivity of the stimulation charge and of the contact localization according to the white or gray matter. The most relevant maps for the scientific community are available for download on f-tract. eu (David et al., 2017) and will be regularly updated during the following months with the addition of more data in the F-TRACT database. This will provide an unprecedented knowledge on the dynamical properties of large fiber tracts in human.

Cost-effectiveness analysis of epilepsy surgery in a controlled cohort of adult patients with intractable partial epilepsy: A 5-year follow-up study.

OBJECTIVE: Despite its well-known effectiveness, the cost-effectiveness of epilepsy surgery has never been demonstrated in France. We compared cost-effectiveness between resective surgery and medical therapy in a controlled cohort of adult patients with partial intractable epilepsy. METHODS: A prospective cohort of adult patients with surgically remediable and medically intractable partial epilepsy was followed over 5 years in the 15 French centers. Effectiveness was defined as 1 year without a seizure, based on the International League Against Epilepsy (ILAE) classification. Clinical outcomes and direct costs were compared between surgical and medical groups. Long-term direct costs and effectiveness were extrapolated over the patients' lifetimes with a Monte-Carlo simulation using a Markov model, and an incremental cost-effectiveness ratio (ICER) was computed. Indirect costs were also evaluated. RESULTS: Among the 289 enrolled surgery candidates, 207 were operable-119 in the surgical group and 88 in the medical group-65 were not operable and not analyzed here, 7 were finally not eligible, and 10 were not followed. The proportion of patients completely seizure-free during the last 12 months (ILAE class 1) was 69.0% in the operated group and 12.3% in the medical group during the second year (p < 0.001), and it was respectively 76.8% and 21% during the fifth year (p < 0.001). Direct costs became significantly lower in the surgical group the third year after surgery, as a result of less antiepileptic drug use. The value of the discounted ICER was 10,406 (95% confidence interval [CI] 10,182-10,634) at 2 years and 2,630 (CI 95% 2,549-2,713) at 5 years. Surgery became cost-effective between 9 and 10 years after surgery, and even earlier if indirect costs were taken into account as well. SIGNIFICANCE: Our study suggests that in addition to being safe and effective, resective surgery of epilepsy is cost-effective in the medium term. It should therefore be considered earlier in the development of epilepsy.

Radiosurgical Corpus Callosotomy for Intractable Epilepsy: Retrospective Long-Term Safety and Efficacy Assessment in 19 Patients an Review of the Literature.

BACKGROUND: Some patients suffering from intractable epileptic seizures, particularly drop attacks (DAs), are nonremediable by curative techniques. Palliative procedure carries a significant rate of surgical and neurological complications. OBJECTIVE: To propose evaluation of safety and efficacy of Gamma Knife corpus callosotomy (GK-CC) as an alternative to microsurgical corpus callosotomy. METHODS: This study included retrospective analysis of 19 patients who underwent GK-CC between 2005 and 2017. RESULTS: Of the 19 patients, 13 (68%) had improvement in seizure control and 6 had no significant improvement. Of the 13/19 (68%) with improvement in seizures, 3 (16%) became completely seizure-free, 2 (11%) became free of DA and generalized tonic-clonic but with residual other seizures, 3 (16%) became free of DA only, and 5 (26%) had >50% reduction in frequency of all seizure types. In the 6 (31%) patients with no appreciable improvement, there were residual untreated commissural fibers and incomplete callosotomy rather than failure of Gamma Knife to disconnect. Seven patients showed a transient mild complication (37% of patients, 33% of the procedures). No permanent complication or neurological consequence was observed during the clinical and radiological workup with a mean of 89 (42-181) months, except 1 patient who had no improvement of epilepsy and then aggravation of the pre-existing cognitive and walking difficulties (Lennox-Gastaut). The median time of improvement after GK-CC was 3 (1-6) months. CONCLUSION: Gamma Knife callosotomy is safe and accurate with comparable efficacy to open callosotomy in this cohort of patients with intractable epilepsy suffering from severe drop attacks.

Specific profiles of new-onset vs. non-inaugural status epilepticus: From diagnosis to 1-year outcome.

While new-onset status epilepticus (NOSE) is a harbinger of chronic epilepsy, prospective medical data are sparse in terms of specifying whether the evolution of status epilepticus (SE) and seizure expression in NOSE resembles what occurs in patients who have already been diagnosed with epilepsy [non-inaugural SE (NISE)] in all aspects apart from its inaugural nature. The aim of this study was to compare the clinical, MRI, and EEG features that could distinguish NOSE from NISE. We conducted a prospective monocentric study in which all patients ≥18 years admitted for SE over a 6-month period were included. A total of 109 patients (63 NISE and 46 NOSE cases) were included. Despite similar modified Rankin scores before SE, several aspects of the clinical history distinguished NOSE from NISE patients. NOSE patients were older and frequently had neurological comorbidity and preexisting cognitive decline, but they had a similar prevalence of alcohol consumption to NISE patients. NOSE and NISE evolve in the same proportions as refractory SE (62.5% NOSE, 61% NISE) and share common features such as the same incidence (33% NOSE, 42% NISE, and p = 0.53) and volumes of peri-ictal abnormalities on MRI. However, in NOSE patients, we observed greater non-convulsive semiology (21.7% NOSE, 6% NISE, and p = 0.02), more periodic lateral discharges on EEG (p = 0.004), later diagnosis, and higher severity according to the STESS and EMSE scales (p < 0.0001). Mortality occurred in 32.6% of NOSE patients and 21% of NISE patients at 1 year (p = 0.19), but with different causes of death occurring at different time points: more early deaths directly linked to SE at 1 month occurred in the NOSE group, while there were more remote deaths linked to causal brain lesions in the NISE group at final follow-up. In survivors, 43.6% of the NOSE cases developed into epilepsy. Despite acute causal brain lesions, the novelty related to its inaugural nature is still too often associated with a delay in diagnosing SE and a poorer outcome, which justifies the need to more clearly specify the various types of SE to constantly raise awareness among clinicians. These results highlight the relevance of including novelty-related criteria, clinical history, and temporality of occurrence in the nosology of SE.

Neuronal hyperexcitability in the Tg2576 mouse model of Alzheimer's disease - the influence of sleep and noradrenergic transmission.

The link between Alzheimer's disease (AD) and network hypersynchrony - manifesting as epileptic activities - received considerable attention in the past decade. However, several questions remain unanswered as to its mechanistic underpinnings. Therefore, our objectives were (1) to better characterise epileptic events in the Tg2576 mouse model throughout the sleep-wake cycle and disease progression via electrophysiological recordings and (2) to explore the involvement of noradrenergic transmission in this pathological hypersynchrony. Over and above confirming the previously described early presence and predominance of epileptic events during rapid-eye-movement (REM) sleep, we also show that these events do not worsen with age and are highly phase-locked to the section of the theta cycle during REM sleep where hippocampal pyramidal cells reach their highest firing probability. Finally, we reveal an antiepileptic mechanism of noradrenergic transmission via α1-adrenoreceptors that could explain the intriguing distribution of epileptic events over the sleep-wake cycle in this model, with potential therapeutic implications in the treatment of the epileptic events occurring in many AD patients.

Early identification of seizure freedom with medical treatment in patients with mesial temporal lobe epilepsy and hippocampal sclerosis.

BACKGROUND: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is usually associated with a poor response to antiseizure medications. We focused on MTLE-HS patients who were seizure free on medication to: (1) determine the clinical factors associated with seizure freedom and (2) develop a machine-learning classifier to better earlier identify those patients. METHODS: We performed a retrospective, multicentric study comparing 64 medically treated seizure-free MTLE-HS patients with 200 surgically treated drug-resistant MTLE-HS patients. First, we collected medical history and seizure semiology data. Then, we developed a machine-learning classifier based on clinical data. RESULTS: Medically treated seizure-free MTLE-HS patients were seizure-free for at least 2 years, and for a median time of 7 years at last follow-up. Compared to drug-resistant MTLE-HS patients, they exhibited: an older age at epilepsy onset (22.5 vs 8.0 years, p < 0.001), a lesser rate of: febrile seizures (39.0% vs 57.5%, p = 0.035), focal aware seizures (previously referred to as aura)(56.7% vs 90.0%, p < 0.001), autonomic focal aware seizures in presence of focal aware seizure (17.6% vs 59.4%, p < 0.001), dystonic posturing of the limbs (9.8% vs 47.0%, p < 0.001), gestural (27.4% vs 94.0%, p < 0.001), oro-alimentary (32.3% vs 75.5%, p < 0.001) or verbal automatisms (12.9% vs 36.0%, p = 0.001). The classifier had a positive predictive value of 0.889, a sensitivity of 0.727, a specificity of 0.962, a negative predictive value of 0.893. CONCLUSIONS: Medically treated seizure-free MTLE-HS patients exhibit a distinct clinical profile. A classifier built with readily available clinical data can identify them accurately with excellent positive predictive value. This may help to individualize the management of MTLE-HS patients according to their expected pharmacosensitivity.

Hidden Objective Memory Deficits Behind Subjective Memory Complaints in Patients With Temporal Lobe Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this work was to test the hypothesis that patients with temporal lobe epilepsy (TLE) with subjective initial memory complaints (not confirmed by an objective standard assessment) and various phenotypes also show objective very long-term memory deficit with accelerated long-term forgetting. We tested patients with TLE with 2 surprise memory tests after 3 weeks: the standard Free and Cued Selective Reminding Test (FCSRT) and Epireal, a new test specifically designed to capture more ecologic aspects of autobiographical memory. METHODS: Forty-seven patients with TLE (12 with hippocampal sclerosis, 12 with amygdala enlargement, 11 with extensive lesions, 12 with normal MRI) who complained about their memory, but for whom the standard neuropsychological assessment did not reveal any memory impairment after a standard delay of 20 minutes, underwent 2 surprise memory tests after 3 weeks. They were compared to 35 healthy controls. RESULTS: After 3 weeks, FCSRT and Epireal recall scores were significantly lower in patients than in controls (p < 0.001). There was no significant correlation between FCSRT and Epireal scores (p = 0.99). Seventy-six percent of patients with TLE had objective impairment on at least 1 of these very long-term memory tests, regardless of the existence and type of lesion or response to antiseizure medication. Easily applicable, Epireal had a higher effect size, detected deficits in 28% more patients, and is a useful addition to the standard workup. DISCUSSION: Assessing long-term memory should be broadened to a wide spectrum of patients with TLE with a memory complaint, regardless of the epileptic syndrome, regardless of whether it is associated with a lesion. This could lead to rethinking TLE nosology associated with memory.

Sleep: The Tip of the Iceberg in the Bidirectional Link Between Alzheimer's Disease and Epilepsy.

The observation that a pathophysiological link might exist between Alzheimer's disease (AD) and epilepsy dates back to the identification of the first cases of the pathology itself and is now strongly supported by an ever-increasing mountain of literature. An overwhelming majority of data suggests not only a higher prevalence of epilepsy in Alzheimer's disease compared to healthy aging, but also that AD patients with a comorbid epileptic syndrome, even subclinical, have a steeper cognitive decline. Moreover, clinical and preclinical investigations have revealed a marked sleep-related increase in the frequency of epileptic activities. This characteristic might provide clues to the pathophysiological pathways underlying this comorbidity. Furthermore, the preferential sleep-related occurrence of epileptic events opens up the possibility that they might hasten cognitive decline by interfering with the delicately orchestrated synchrony of oscillatory activities implicated in sleep-related memory consolidation. Therefore, we scrutinized the literature for mechanisms that might promote sleep-related epileptic activity in AD and, possibly dementia onset in epilepsy, and we also aimed to determine to what degree and through which processes such events might alter the progression of AD. Finally, we discuss the implications for patient care and try to identify a common basis for methodological considerations for future research and clinical practice.

CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients.

CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.

Generalized convulsive status epilepticus management in adults: a cohort study with evaluation of professional practice.

PURPOSE: Generalized convulsive status epilepticus (GCSE) needs immediate management. Despite guidelines, adherence to management protocols is often poor, this contributing to poor outcome. We aimed to evaluate the usefulness of a management protocol in GCSE. METHODS: This is a prospective population-based study of consecutive adults with GCSE in Haute-Garonne district, France. Demographics and treatment procedures were documented. Factors associated with seizure termination and refractoriness were analyzed using logistic regression. RESULTS: One hundred eighteen episodes in 111 adults (mean age 55 years) between October 2006 and February 2008 were included. SE was convulsive in 101 episodes. Incidence was 6.6 per 100,000 and case fatality was 9%. Adequate initial treatment according to protocol was observed in 38%; 64% were treated out-of-hospital, and SE was refractory in 27% [no response after two antiepileptic drugs (AED)]. Patients who received adequate first-line treatment were 6.8 times [95% confidence interval (CI) 2.8-16.9] more likely to have seizure termination, with 74% versus 29% efficacy rate (p < 0.0001). Inadequate initial management was 4.7 times (1.9-11.1) more likely to need several benzodiazepine doses (p = 0.0004) and 9.1 times (3.7-20) more likely to require a long-acting AED as next treatment (p < 0.0001). Seizure termination after initial treatment was associated with decreased intensive care unit stay [1 (1-2) versus 2 (1-5.5) days, p < 0.0001] and hospital stay [3 (2-11) versus 7 (3-18) days, p = 0.009]. DISCUSSION: GCSE termination and outcome seem clearly associated with adherence to treatment protocol. Results add to the debate on appropriate allocation of resources for out-of-hospital treatment, licensed drugs, and achievement of guideline implementation to improve SE outcome.

Impaired consciousness during temporal lobe seizures is related to increased long-distance cortical-subcortical synchronization.

Loss of consciousness (LOC) is a dramatic clinical manifestation of temporal lobe seizures. Its underlying mechanism could involve altered coordinated neuronal activity between the brain regions that support conscious information processing. The consciousness access hypothesis assumes the existence of a global workspace in which information becomes available via synchronized activity within neuronal modules, often widely distributed throughout the brain. Re-entry loops and, in particular, thalamo-cortical communication would be crucial to functionally bind different modules together. In the present investigation, we used intracranial recordings of cortical and subcortical structures in 12 patients, with intractable temporal lobe epilepsy (TLE), as part of their presurgical evaluation to investigate the relationship between states of consciousness and neuronal activity within the brain. The synchronization of electroencephalography signals between distant regions was estimated as a function of time by using non-linear regression analysis. We report that LOC occurring during temporal lobe seizures is characterized by increased long-distance synchronization between structures that are critical in processing awareness, including thalamus (Th) and parietal cortices. The degree of LOC was found to correlate with the amount of synchronization in thalamo-cortical systems. We suggest that excessive synchronization overloads the structures involved in consciousness processing, preventing them from treating incoming information, thus resulting in LOC.

Post-traumatic Stress Disorder With Flashbacks of an Old Childhood Memory Triggered by Right Temporal Lobe Epilepsy Surgery in Adulthood.

BACKGROUND: A plethora of data show that the hippocampus and the amygdala are involved in post-traumatic stress disorder (PTSD). Neural dysfunctions leading to PTSD (e.g. how the amygdala and the hippocampus are altered) are only partially known. The unusual case of a patient presenting with refractory epilepsy and developing PTSD immediately after surgery is described. Such symptoms in epileptic patients may help to explore PTSD mechanisms. CASE REPORT: A 41-year-old male suffering from partial refractory temporal lobe epilepsy was operated in May 2017. A right amygdala, hippocampus, and temporal pole selective resection was performed. He experienced intense PTSD symptoms 1 month after surgery. He complained about repetitive intrusive memories of abuse. The PTSD checklist score was equal to 62/80. He reported a history of childhood abuse: physical and emotional abuse as well as emotional negligence, assessed with the Childhood Trauma Questionnaire. No other medical history was recorded. He never complained about PTSD or any other psychiatric symptoms before surgery. CONCLUSION: this case indicates that PTSD may occur after temporal lobe epilepsy surgery and may specifically stem, as in this context, from the excision of part of the medial temporal lobe structures. Although rarely reported, PTSD may be undiagnosed when not selectively detected via multi-disciplinary neurological and psychiatric management, in the preoperative period and the immediate and delayed postoperative period.