Common Epilepsy Research Articles

Silencing of miR-132-3p protects against neuronal injury following status epilepticus by inhibiting IL-1β-induced reactive astrocyte (A1) polarization.

Mesial temporal lobe epilepsy (MTLE) is one of the most common refractory epilepsies and is usually accompanied by a range of brain pathological changes, such as neuronal injury and astrocytosis. Naïve astrocytes are readily converted to cytotoxic reactive astrocytes (A1) in response to inflammatory stimulation, suppressing the polarization of A1 protects against neuronal death in early central nervous system injury. Our previous study found that pro-inflammatory cytokines and miR-132-3p (hereinafter referred to as "miR-132") expression were upregulated, but how miR-132 affected reactive astrocyte polarization and neuronal damage during epilepsy is not fully understood. Here, we aimed to explore the effect and mechanism of miR-132 on A1 polarization. Our results confirmed that A1 markers were significantly elevated in the hippocampus of MTLE rats and IL-1β-treated primary astrocytes. In vivo, knockdown of miR-132 by lateral ventricular injection reduced A1 astrocytes, neuronal loss, mossy fiber sprouting, and remitted the severity of status epilepticus and the recurrence of spontaneous recurrent seizures. In vitro, the neuronal cell viability and axon length were reduced by additional treatment with A1 astrocyte conditioned media (ACM), and downregulation of astrocyte miR-132 rescued the inhibition of cell activity by A1 ACM, while the length of axons was further inhibited. The regulation of miR-132 on A1 astrocytes may be related to its target gene expression. Our results show that interfering with astrocyte polarization may be a breakthrough in the treatment of refractory epilepsy, which may extend to the research of other astrocyte polarization-mediated brain injuries.

Alterations in the default mode network in rolandic epilepsy with mild spike-wave index in non-rapid eye movement sleep.

PurposeRolandic epilepsy (RE) is one of the most common epilepsy syndromes during childhood. The aim of this study was to investigate the alterations in the default mode network (DMN) of RE patients whose spike-wave index (SWI) was within the 50–85% range during non-rapid eye movement (NREM) during sleep, as well as to detect early neuroimaging markers.MethodsResting-state data was recorded for each subject using magnetoencephalography (MEG). DMN-related brain regions were chosen as regions of interest. The spectral power and functional connectivity (FC) of the DMN were estimated through the use of minimum norm estimation (MNE) combined with Welch technique and corrected amplitude envelope correlation (AEC-c).ResultsThe patient group included 20 patients with NREM phase 50% ≤ SWI < 85% (mild SWI group), and 18 typical RE patients (SWI < 50% group). At the regional level, the mild SWI group exhibited enhanced spectral power in the delta band of the bilateral posterial cingulate cortex and attenuated the spectral power in the alpha band of the bilateral posterial cingulate cortex. Enhanced spectral power in the bilateral precuneus (PCu) in the delta band and attenuated spectral power in the right lateral temporal cortex (LTC) in the alpha band were common across all RE patients. At the FC level, patients in the mild SWI group indicated increased AEC-c values between the bilateral posterial cingulate cortex in the delta band and between the left medial frontal cortex (MFC) and bilateral posterial cingulate cortex in the alpha band. Increased AEC-c values between the right PCu and left MFC in the delta band, and between the left PCu and right MFC in the theta band, were common across all RE patients. Moreover, the spectral power in the bilateral posterial cingulate cortex in the alpha band and the AEC-c value between the bilateral posterial cingulate cortex in the delta band demonstrated good discrimination ability.ConclusionThe spectral power of the bilateral posterior cingulate cortex (PCC) in the alpha band and the AEC-c value between the bilateral PCC in the delta band may be promising indicators of early differentiation between mild SWI and typical RE.

An aqueous extract of Syzygium cumini protects against kainate-induced status epilepticus and amnesia: evidence for antioxidant and anti-inflammatory intervention.

Temporal lobe epilepsy is the most common drug-resistant epilepsy. To cure epilepsy, drugs must target the mechanisms at the origin of seizures. Thus, the present investigation aimed to evaluate the antiepileptic- and anti-amnesic-like effects of an aqueous extract of Syzygium cumini against kainate-induced status epilepticus in mice, and possible mechanisms of action. Mice were divided into 7 groups and treated as follows: normal group or kainate group received po distilled water (10 mL/kg), four test groups received Syzygium cumini (28.8, 72, 144, and 288mg/kg, po), and the positive control group treated intraperitoneally (ip) with sodium valproate (300mg/kg). An extra group of normal mice was treated with piracetam (200mg/kg, po). Treatments were administered 60min before the induction of status epilepticus with kainate (15mg/kg, ip), and continued daily throughout behavioral testing. Twenty-four hours after the induction, T-maze and Morris water maze tasks were successively performed. The animals were then sacrificed and some markers of oxidative stress and neuroinflammation were estimated in the hippocampus. The extract significantly prevented status epilepticus and mortality. In the T-maze, the aqueous extract markedly increased the time spent and the number of entries in the discriminated arm. In the Morris water maze, the extract significantly increased the time spent in the target quadrant during the retention phase. Furthermore, the aqueous extract induced a significant reduction of oxidative stress and neuroinflammation. These results suggest that the aqueous extract of Syzygium cumini has antiepileptic- and anti-amnesic-like effects, likely mediated in part by antioxidant and anti-inflammatory activities.

Abnormal percent amplitude of fluctuation and functional connectivity within and between networks in benign epilepsy with centrotemporal spikes

BackgroundBenign epilepsy with centrotemporal spikes (BECTS) is one of the most common childhood epilepsy syndromes. The neural basis of BECTS is still poorly understood. This study aimed to further investigate the possible neural mechanisms of BECTS by comparing percent amplitude of fluctuation (PerAF) of resting-state functional magnetic resonance imaging (RS-fMRI) signal of each brain voxel and connectivity within and between related networks in children with BECTS and healthy controls (HCs). MethodsFirstly, we used PerAF method to investigate brain functional alteration and defined the regions of interest (ROIs) where children with BECTS exhibited significant PerAF alterations compared to HCs. We then divided these ROIs into different networks based on previous findings and investigated alterations of functional connectivity within and between networks in children with BECTS. Receiver operating characteristic (ROC) curve was employed to assess the reliable biomarker for distinguishing children with BECTS from HCs based on the intergroup PerAF differences. ResultsChildren with BECTS showed decreased PerAF in the left middle frontal cortex (MFC), right precentral gyrus, left precuneus (PCUN), bilateral posterior cingulate cortex (PCC), left angular gyrus, left inferior parietal lobule (IPL), right supplementary motor area (SMA) and left primary somatosensory cortex (S1) compared to HCs. The IPL and PCC exhibited higher classification power by ROC analysis. Moreover, our findings exhibited increased Intra-network connectivity in the default mode network (DMN), and increased inter-network connectivity of the sensorimotor network (SMN) with Broca's area and DMN. ConclusionsOur study investigated the abnormal PerAF and functional brain networks in children with BECTS, which might provide new insights into the pathological mechanisms of BECTS.

Resting-State EEG Functional Connectivity in Children with Rolandic Spikes with or without Clinical Seizures.

Alterations in dynamic brain network function are increasingly recognized in epilepsy. Benign childhood epilepsy with centrotemporal spikes (BECTS), or benign rolandic seizures, is the most common idiopathic focal epilepsy in children. In this study, we analyzed EEG functional connectivity (FC) among children with rolandic spikes with or without clinical seizures as compared to controls, to investigate the relationship between FC and clinical parameters in children with rolandic spikes. The FC analysis based on graph theory and network-based statistics in different frequency bands evaluated global efficiency, clustering coefficient, betweenness centrality, and nodal strength in four frequency bands. Similar to BECTS patients with seizures, children with rolandic spikes without seizures had significantly increased global efficiency, mean clustering coefficient, mean nodal strength, and connectivity strength, specifically in the theta frequency band at almost all proportional thresholds, compared with age-matched controls. Decreased mean betweenness centrality was only present in BECTS patients with seizures. Age at seizure onset was significantly positively associated with the strength of EEG-FC. The decreased function of betweenness centrality was only presented in BECTS patients with clinical seizures, suggesting weaker local connectivity may lower the seizure threshold. These findings may affect treatment policy in children with rolandic spikes.

Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

ObjectiveRecent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross‐sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE‐HS) correlate with clinical features.MethodsWe extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1‐weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA‐Epilepsy consortium, comprising 804 people with MTLE‐HS and 1625 healthy controls from 25 centers. Features with a moderate case–control effect size (Cohen d ≥ .5) were used to train an event‐based model (EBM), which estimates a sequence of disease‐specific biomarker changes from cross‐sectional data and assigns a biomarker‐based fine‐grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance.ResultsIn MTLE‐HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10−16), age at onset (ρ = −.18, p = 9.82 × 10−7), and ASM resistance (area under the curve = .59, p = .043, Mann–Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE‐HS with mild or nondetectable abnormality on T1W MRI.SignificanceFrom cross‐sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE‐HS subjects in other cohorts and help establish connections between imaging‐based progression staging and clinical features.

Impact of Genetic Testing on Therapeutic Decision-Making in Childhood-Onset Epilepsies-a Study in a Tertiary Epilepsy Center.

We assessed the frequency of pediatric monogenic epilepsies and precision therapies at a tertiary epilepsy center. We analyzed medical records of children, born in 2006-2011 and followed at the Danish Epilepsy Center from January to December 2015; 357 patients were identified, of whom 27 without epilepsy and 35 with acquired brain damage were excluded. Of the remaining 295 children, 188 were consented for study inclusion and genetic testing. At inclusion, 86/188 had a preexisting genetic diagnosis and did not undergo further genetic testing. The 102 genetically unsolved patients underwent WES, which identified a (likely) pathogenic variant in eight patients and a highly relevant variant of unknown significance (VUS) in seven additional patients. Single nucleotide polymorphism array was performed in the remaining 87 patients and revealed no (likely) pathogenic copy number variants (CNVs). Patients with a genetic diagnosis had a significantly lower median age at seizure onset and more often had febrile seizures, status epilepticus, or neurodevelopmental impairment compared to those who remained genetically unsolved. Most common epilepsies were focal or multifocal epilepsies and developmental and epileptic encephalopathies (DDEs). Fifty-three patients, with a putative genetic diagnosis, were potentially eligible for precision therapy approaches. Indeed, genetic diagnosis enabled treatment adjustment in 32/53 (60%); 30/32 (93%) patients experienced at least a 50% reduction in seizure burden while only 4/32 (12.5%) became seizure-free. In summary, a genetic diagnosis was achieved in approximately 50% of patients with non-acquired epilepsy enabling precision therapy approaches in half of the patients, a strategy that results in > 50% reduction in seizure burden, in the majority of the treated patients.

Epilepsy and other comorbidities in Down syndrome

AbstractDown syndrome (DS) is the most common cause of intellectual disability. Due to many genetic and biochemical aberrations, people with DS suffer from several somatic disorders and concomitant diseases. Epilepsies occur more often than in the normal population, but less often than with intellectual disability of other causes. Epilepsies in DS have a trimodal distribution with age-related phenotypes, etiologies, and prognosis. The most common epilepsy syndrome in infancy is the often-self-limiting West syndrome; if Lennox–Gastaut syndrome occurs in the later course of development, the seizure prognosis worsens significantly. From the fourth decade of life, myoclonic epilepsy often occurs, which in combination with rapidly progressive Alzheimer’s dementia is life-limiting within a few years.

Multimodal connectome biomarkers of cognitive and affective dysfunction in the common epilepsies.

Epilepsy is one of the most common chronic neurological conditions, traditionally defined as a disorder of recurrent seizures. Cognitive and affective dysfunction are increasingly recognized as core disease dimensions and can affect patient well-being, sometimes more than the seizures themselves. Connectome-based approaches hold immense promise for revealing mechanisms that contribute to dysfunction and to identify biomarkers. Our review discusses emerging multimodal neuroimaging and connectomics studies that highlight network substrates of cognitive/affective dysfunction in the common epilepsies. We first discuss work in drug-resistant epilepsy syndromes, that is, temporal lobe epilepsy, related to mesiotemporal sclerosis (TLE), and extratemporal epilepsy (ETE), related to malformations of cortical development. While these are traditionally conceptualized as ‘focal’ epilepsies, many patients present with broad structural and functional anomalies. Moreover, the extent of distributed changes contributes to difficulties in multiple cognitive domains as well as affective-behavioral challenges. We also review work in idiopathic generalized epilepsy (IGE), a subset of generalized epilepsy syndromes that involve subcortico-cortical circuits. Overall, neuroimaging and network neuroscience studies point to both shared and syndrome-specific connectome signatures of dysfunction across TLE, ETE, and IGE. Lastly, we point to current gaps in the literature and formulate recommendations for future research.

Effectiveness and Safety of Oxcarbazepine vs. Levetiracetam as Monotherapy for Infantile Focal Epilepsy: A Longitudinal Cohort Study.

ObjectiveThis study aimed to compare the effectiveness and safety of oxcarbazepine (OXC) vs. levetiracetam (LEV) for treating infantile focal epilepsy in a longitudinal cohort study.MethodsWe enrolled 187 consecutive patients aged 2–24 months who received OXC or LEV as initial monotherapy; 161 patients completed the study. The longitudinal analysis involved anti-seizure medication (ASM) responsiveness, safety, the establishment of epilepsy syndrome, and etiology over a median follow-up of 2 years (interquartile range [IQR] 1.6–2.4). The relative efficacy and retention rates of OXC vs. LEV were evaluated using generalized linear regression models and the Cox proportional hazards model.ResultsThe 161 patients who completed the study had comparable baseline demographics and clinical variables between the OXC group (n = 83) and LEV group (n = 78). Overall, the mean age at onset was 6 months (IQR 4.3–9). The most common epilepsy syndrome was self-limited familial/non-familial infantile epilepsy (54.7%). Epilepsy was related to genetic and unknown causes in 34.2 and 52.2% of the patients, respectively. OXC achieved significantly higher responses than LEV for seizure freedom (risk ratio [RR] = 1.71, 95% confidence interval [CI] = 1.28–2.73, P < 0.001) and 12-month retention rate after onset (hazard ratio [HR] = 1.84, 95% CI = 1.15–2.95, P = 0.007). Moreover, OXC showed more obvious effects for patients aged < 1 year diagnosed with self-limited familial/non-familial infantile epilepsy and non-syndromic epilepsy with genetic or unknown causes. The adverse events related to both OXC and LEV were well-tolerated.SignificanceOXC could be an alternative to LEV for treating infantile focal epilepsy. OXC monotherapy can be considered first-line treatment for patients aged <12 months and those with epilepsy without developmental and epileptic encephalopathy.

SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility

Mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures is associated with common variation at rs7587026, located in the promoter region of SCN1A. We sought to explore possible underlying mechanisms. SCN1A expression was analysed in hippocampal biopsy specimens of individuals with mesial temporal lobe epilepsy with hippocampal sclerosis who underwent surgical treatment, and hippocampal neuronal cell loss was quantitatively assessed using immunohistochemistry. In healthy individuals, hippocampal volume was measured using MRI. Analyses were performed stratified by rs7587026 type. To study the functional consequences of increased SCN1A expression, we generated, using transposon-mediated bacterial artificial chromosome transgenesis, a zebrafish line expressing exogenous scn1a, and performed EEG analysis on larval optic tecta at 4 day post-fertilization. Finally, we used an in vitro promoter analysis to study whether the genetic motif containing rs7587026 influences promoter activity. Hippocampal SCN1A expression differed by rs7587026 genotype (Kruskal–Wallis test P = 0.004). Individuals homozygous for the minor allele showed significantly increased expression compared to those homozygous for the major allele (Dunn’s test P = 0.003), and to heterozygotes (Dunn’s test P = 0.035). No statistically significant differences in hippocampal neuronal cell loss were observed between the three genotypes. Among 597 healthy participants, individuals homozygous for the minor allele at rs7587026 displayed significantly reduced mean hippocampal volume compared to major allele homozygotes (Cohen’s D = − 0.28, P = 0.02), and to heterozygotes (Cohen’s D = − 0.36, P = 0.009). Compared to wild type, scn1lab-overexpressing zebrafish larvae exhibited more frequent spontaneous seizures [one-way ANOVA F(4,54) = 6.95 (P < 0.001)]. The number of EEG discharges correlated with the level of scn1lab overexpression [one-way ANOVA F(4,15) = 10.75 (P < 0.001]. Finally, we showed that a 50 bp promoter motif containing rs7587026 exerts a strong regulatory role on SCN1A expression, though we could not directly link this to rs7587026 itself. Our results develop the mechanistic link between rs7587026 and mesial temporal lobe epilepsy with hippocampal sclerosis and a history of febrile seizures. Furthermore, we propose that quantitative precision may be important when increasing SCN1A expression in current strategies aiming to treat seizures in conditions involving SCN1A haploinsufficiency, such as Dravet syndrome.

Ameliorating effect of ketogenic diet on acute status epilepticus: Insights into biochemical and histological changes in rat hippocampus.

This study aimed to evaluate the potential neuroprotective effects of ketogenic diet (KD) against the neuronal disruptions induced by SE in lithium-pilocarpine rat model of status epilepticus (SE). Four groups of female rats include; groups I and III received standard diet and groups II and IV received KD for 3 weeks. Groups I and II were left untreated, while groups III and IV were injected with LiCl (127 mg/kg, i.p.) followed by pilocarpine HCl (10mg/kg, i.p.) 18-24h later, repeatedly, till induction of SE. 72 h post-SE, KD effectively ameliorated the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters and the oxidative stress indices, increased adenine nucleotides and decreased immunoreactivity of iNOS, TNFα, glial fibrillary acidic protein, and synaptophysin. Thiswas in association with improvement in inflammatory response and neuronal tissue characteristics in hippocampus of SE rats. Histological changes showed preservation of neuronal integrity. These findings highlight the protective effects of KD in the acute phase post-SE via ameliorating biochemical and histological changes involved. PRACTICAL APPLICATIONS: Epilepsy is the fourth most common neurological disorder that requires lifelong treatment. It stigmatizes patients and their families. The use of the ketogenic diet (KD) as a therapy for epilepsy developed from observations that fasting could reduce seizures. From 1920s, the KD was a common epilepsy treatment until it was gradually superseded by anticonvulsant drugs so that by the 1980s it was rarely used. However, there has been a resurgence of interest and usage of the KD for epilepsy since the turn of the century. Despite its long history, the mechanisms by which KD exhibits its anti-seizure action are not fully understood. Our study aims to identify the mechanism of KD which may help further studies to achieve the same benefits with a drug or supplement to overcome its unpalatability and gastrointestinal side effects.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Hemp Dispensaries in NC Promote CBD to Treat Pain and Offer low-CBD/high Price Products

Demand for products containing cannabidiol (CBD), a non-intoxicating hemp/cannabis derived compound for the treatment of pain is growing as states legalize medicinal cannabis programs. Currently, only one prescription medication containing CBD is approved by the FDA; Epidiolex, which is used to treat resistant seizures syndromes in children. The FDA has deemed it illegal for companies to make any other medical/therapeutic or health claims about CBD products. Some states, such as North Carolina, have legalized CBD using compassionate programs to promote the access to CBD for patients with these epileptic syndromes. The goal of our study was to determine whether the CBD program in NC complies with FDA advertisement requirements, or these compounds are illegally advertised to treat pain. We also investigated whether the CBD program in NC provides an economic advantage over other pain medication or Epidiolex. We selected the 10 most populated cities of NC and randomly chose 3 hemp/CBD shops (dispensaries) from each city. We collected online information of products from the dispensary websites. Our results show that four types of products are equally present: edible, oral, inhalable, and topical. A word analysis of product description revealed that "pain relief" was the most common medical claim, and epilepsy or seizures were absent. Health claims were mostly related to skin and general wellbeing. The total CBD content of the majority of products was less than 500 mg. The average price for 300 mg of CBD in any type of product is $25, and there was a positive correlation between CBD content and price. We conclude that the NC CBD dispensaries do not comply with FDA requirements or the NC Epilepsy Alternative Treatment Act and heavily promote CBD for the treatment of pain. NC CBD products contain non-clinically meaningful CBD concentrations and higher prices than OTC analgesics or Epidiolex. Grant support from Pilot Award WFU Center for Research on Substance Use and Addiction.

Genetic Epilepsy Syndromes.

This article reviews the clinical features, typical EEG findings, treatment, prognosis, and underlying molecular etiologies of the more common genetic epilepsy syndromes. Genetic generalized epilepsy, self-limited focal epilepsy of childhood, self-limited neonatal and infantile epilepsy, select developmental and epileptic encephalopathies, progressive myoclonus epilepsies, sleep-related hypermotor epilepsy, photosensitive occipital lobe epilepsy, and focal epilepsy with auditory features are discussed. Also reviewed are two familial epilepsy syndromes: genetic epilepsy with febrile seizures plus and familial focal epilepsy with variable foci. Recent years have seen considerable advances in our understanding of the genetic factors underlying genetic epilepsy syndromes. New therapies are emerging for some of these conditions; in some cases, these precision medicine approaches may dramatically improve the prognosis. Many recognizable genetic epilepsy syndromes exist, the identification of which is a crucial skill for neurologists, particularly those who work with children. Proper diagnosis of the electroclinical syndrome allows for appropriate treatment choices and counseling regarding prognosis and possible comorbidities.

Neuroimaging and thalamic connectomics in epilepsy neuromodulation

Neuromodulation is an increasingly utilized therapy for the treatment of people with drug-resistant epilepsy. To date, the most common and effective target has been the thalamus, which is known to play a key role in multiple forms of epilepsy. Neuroimaging has facilitated rapid developments in the understanding of functional targets, surgical and programming techniques, and the effects of thalamic stimulation. In this review, the role of neuroimaging in neuromodulation is explored. First, the structural and functional changes of the thalamus in common epilepsy syndromes are discussed as the rationale for neuromodulation of the thalamus. Next, methods for imaging different thalamic nuclei are presented, as well as rationale for the need of direct surgical targeting rather than reliance on traditional stereotactic coordinates. Lastly, we discuss the potential role of neuroimaging in assessing the effects of thalamic stimulation and as a potential biomarker for neuromodulation outcomes.

Deep feature fusion based childhood epilepsy syndrome classification from electroencephalogram

Accurate classification of the children’s epilepsy syndrome is vital to the diagnosis and treatment of epilepsy. But existing literature mainly focuses on seizure detection and few attention has been paid to the children’s epilepsy syndrome classification. In this paper, we present a study on the classification of two most common epilepsy syndromes: the benign childhood epilepsy with centro-temporal spikes (BECT) and the infantile spasms (also known as the WEST syndrome), recorded from the Children’s Hospital, Zhejiang University School of Medicine (CHZU). A novel feature fusion model based on the deep transfer learning and the conventional time–frequency representation of the scalp electroencephalogram (EEG) is developed for the epilepsy syndrome characterization. A fully connected network is constructed for the feature learning and syndrome classification. Experiments on the CHZU database show that the proposed algorithm can offer an average of 92.35% classification accuracy on the BECT and WEST syndromes and their corresponding normal cases.

Psychiatric and Behavioural Side Effects Associated With Perampanel in Patients With Temporal Lobe Epilepsy. A Real-World Experience.

Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were “irritability” for both groups and “aggression” for patients with other focal epilepsies.

Treatment of Focal-Onset Seizures in Children: Should This Be More Etiology-Driven?

To accelerate the process of licensing antiseizure medication (ASM) in children, extrapolation of efficacy data for focal-onset seizures from adults to children ≥2 or ≥4 years of age is now accepted. We summarized the efficacy evidence from randomized, controlled trials that was used to grant approval for the pediatric indication of focal-onset seizures for the different ASMs available in Europe. Data from high-quality randomized, controlled trials in young children are limited, especially on the use of ASMs in monotherapy. Licensure trials are typically focused on seizure type irrespective of etiology or epilepsy syndrome. We elaborate on the importance of etiology- or syndrome-driven research and treatment, illustrating this with examples of childhood epilepsy syndromes characterized by predominantly focal-onset seizures. Some of these syndromes respond well to standard ASMs used for focal-onset seizures, but others would benefit from a more etiology- or syndrome-driven approach. Advances in molecular genetics and neuroimaging have made it possible to reveal the underlying cause of a child's epilepsy and tailor research and treatment. More high-quality randomized, controlled trials based on etiology or syndrome type are needed, including those assessing effects on cognition and behavior. In addition, study designs such as “N-of-1 trials” could elucidate possible new treatment options in rare epilepsies. Broadening incentives currently in place to stimulate the development and marketing of drugs for rare diseases (applicable to some epilepsy syndromes) to more common pediatric epilepsy types and syndromes might be a means to enable high-quality trials, and ultimately allow more evidence-based treatment in children.

Electrical status epilepticus during sleep (ESES) in benign childhood epilepsy with Centrotemporal spikes (BCECTS): insights into predictive factors, and clinical and EEG outcomes.

Benign childhood epilepsy with centro-temporal spikes (BCECTS), otherwise known as benign rolandic epilepsy, is the most common focal epilepsy in childhood. This study aimed to evaluate the development and resolution of ESES in children with BCECTS and evaluate the clinical and electroencephalography (EEG) parameters associated with prognosis. Resolution of ESES was defined as the reduction of the spike-wave index (SWI) to <50%. The SWI short method, measurements from the first 180 s of non-rapid eye movement; and the conventional method, measurements from total NREM stage 2, SW count during the first 60 and 180 s of NREM, SW localization, and ESES type were determined. Of a total of 126 BCECTS patients, 33, including 13 females, 20 males, who developed ESES during follow-up, were included in the study. ESES remission was observed in 42.4% (n = 14) of the patients. The median time to remission was 10.5 months. The rate of resolution was 87.9 % for the entire population. The mean age at resolution was 9.8 ± 2.05 years and the mean time to resolution was 8.8 months. The data demonstrated that age at ESES diagnosis, the time between BCECTS diagnosis and the onset of ESES, time to resolution of ESES, ESES remission, and seizure freedom after ESES were significantly associated with prognosis. The early recognition of ESES evolution in children with BECTS, the better understanding of the relationship between age at ESES diagnosis and remission and prognosis, and timely intervention can prevent long-term sequelae.