Adult Epilepsy Research Articles

Diagnostics and age-related evolution of Lennox–Gastaut syndrome. Management in diverse patient age periods

Lennox–Gastaut syndrome is an epileptic encephalopathy with onset in childhood. The classical triad of diagnostic criteria is well known: 1) presence of various types of refractory epileptic seizures (tonic, atypical absences, myoclonic, tonic/atonic drop attacks, generalized tonic-clonic, focal); 2) cognitive disorders with frequent behavioral disorders (not always evident by the beginning of epileptic seizures); 3) generalized, slow (≤2.5 Hz) spike-wave activity of wakefulness and generalized paroxysmal fast activity on sleep electroencephalogram. Despite the seizure onset usually occurring before the age of 8 (peak at 3–5) years old, the Lennox–Gastaut syndrome is often featured with a lifelong course. Many patients with this syndrome suffer from refractory epilepsy in adulthood, however, not always being provided a proper syndromological diagnosis. Expanding the criteria to diagnose the Lennox–Gastaut syndrome discussed here would allow to choose a proper treatment algorithm. Rufinamide is the drug of the second choice in the adjunctive therapy of epileptic seizures associated with Lennox–Gastaut syndrome. However, a pediatric-to-adult clinic transition of patients with Lennox–Gastaut syndrome may pose some obstacles. Herein, an effective patient management requires not only seizure control, but also improvement of patient's quality of life by influencing cognitive and behavioral issues, sleep disorders, disability (both physical and social), educational problems and employment.

Effects of cenobamate on cognitive performance of epilepsy patients

PurposeCenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance. MethodEfficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions. ResultsThe median CNB dose at T1 was 125 mg/day (range: 50 – 250 mg/day). Most patients received 2–3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p < .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency. ConclusionMost of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

EEG Markers of Treatment Resistance in Idiopathic Generalized Epilepsy: From Standard EEG Findings to Advanced Signal Analysis.

Idiopathic generalized epilepsy (IGE) represents a common form of epilepsy in both adult and pediatric epilepsy units. Although IGE has been long considered a relatively benign epilepsy syndrome, a remarkable proportion of patients could be refractory to treatment. While some clinical prognostic factors have been largely validated among IGE patients, the impact of routine electroencephalography (EEG) findings in predicting drug resistance is still controversial and a growing number of authors highlighted the potential importance of capturing the sleep state in this setting. In addition, the development of advanced computational techniques to analyze EEG data has opened new opportunities in the identification of reliable and reproducible biomarkers of drug resistance in IGE patients. In this manuscript, we summarize the EEG findings associated with treatment resistance in IGE by reviewing the results of studies considering standard EEGs, 24-h EEG recordings, and resting-state protocols. We discuss the role of 24-h EEG recordings in assessing seizure recurrence in light of the potential prognostic relevance of generalized fast discharges occurring during sleep. In addition, we highlight new and promising biomarkers as identified by advanced EEG analysis, including hypothesis-driven functional connectivity measures of background activity and data-driven quantitative findings revealed by machine learning approaches. Finally, we thoroughly discuss the methodological limitations observed in existing studies and briefly outline future directions to identify reliable and replicable EEG biomarkers in IGE patients.

Investigation on the Influencing Factors Related to Quality of Life of Adult Epilepsy Patients in Wenzhou, China, Based on Structural Equation Model.

Objective The aim of the study is to investigate the influencing factors of quality of life in adult patients with epilepsy in Wenzhou in China. Methods A total of 190 patients who visited our hospital from July 2019 to February 2021 were included in the study. Demographic data and disease status were collected. Moreover, QOLIE-31, PSQI, ESS, HAMD-17, and GAD-7 were used in the questionnaire survey. Structural equation model fitting was used to analyze the influencing factors of quality of life in adult patients with epilepsy. Results The scores of the dimension of onset worry in men were greater than those of women (P = 0.049), and the scores of the dimension of life satisfaction were lower than women (P = 0.047). The scores of cognitive function decreased with age (P = 0.047). The scores of quality of life of unemployed and drinking patients significantly decreased (P < 0.05). The score of quality of life positively correlated with good economic status and family relations (P < 0.05). The score of emotional health increased first and then decreased with the course of the disease. With the decrease in seizure frequency and the extension of months without a seizure, the score of quality of life gradually increased. Furthermore, the structural equation model showed that health status was directly correlated to the quality of life of patients with epilepsy. Conclusion Male, unemployment, drinking, older age, and disease are negatively related to the quality of life in patients with epilepsy. However, good economic status, good family relations, and good colleague relationships are positively related to the quality of life.

Exploring seizure management in hospitals, unmet need, and the impact of the COVID-19 pandemic on seizure presentations to hospital

PurposeThis study assesses investigations, referrals and admissions in patients presenting to the Emergency Department (ED) with seizures, and the effect of the COVID-19 pandemic on such management. Outcomes in patients with learning disabilities, active significant mental health concerns, and from the most socioeconomically deprived areas were compared to those of the general cohort. MethodsInvestigations, referrals and admissions were recorded for 120 patients across two cohorts; pre-pandemic (September 2019) and during the pandemic (December 2020). Retrospective review of individual patient electronic health care records was used for data collection. ResultsThere was a decrease in patient numbers from 2019 to 2020. A greater proportion of patients presented with organic cause seizures and fewer presented with non-epileptic attacks. Frequent use of CT heads (45%) is likely to represent improper use of limited resources. There were low referral rates, both to acute neurology (28%) and to the adult epilepsy team (32%). Patients with active significant mental health concerns were significantly less likely to be referred to neurology or admitted. ConclusionsDespite a greater proportion of admissions during the Covid-19 pandemic, referrals to acute neurology and the epilepsy team remained low. Failure to refer prevents the most vulnerable seizure patients from receiving appropriate support, as seen in patients with active significant mental health concerns. Neurology staff were unaware of a significant number of patients presenting with seizures, which is of concern in an already over-stretched department. This offers an opportunity to improve care for people with epilepsy.

Self-perceived burden and associated factors in Chinese adult epilepsy patients: A cross-sectional study.

ObjectivesEpilepsy requires long-term or lifelong treatment, and patients are prone to financial, emotional and psychological burdens that can cause psychological changes during the treatment process. This study aimed to describe the prevalence and associated factors of Self-Perceived Burden (SPB) in Chinese adult epilepsy patients, informing the treatment and nursing of epilepsy.MethodsA total of 143 adult epilepsy patients were included in this study, and the clinical questionnaire survey was conducted at the Third Xiangya Hospital of Central South University in Hunan, China, from March 2022 to June 2022. The sociodemographic and clinical characteristics of adult epilepsy patients were collected using a self-developed questionnaire, and the data on SPB, stigma and quality of life were collected through the Self-Perceived Burden Scale (SPBS), Kilifi Stigma Scale for Epilepsy (KSSE) and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Multiple linear regression analysis was used to determine the associated factors influencing SPB in adult epilepsy patients.ResultsThe average score of SPBS for the 143 adult epilepsy patients was 30.77 (SD = 9.06), and 89.5% of them had obvious SPB. The results of the univariate analysis showed that residence, monthly household income, duration of epilepsy, type of medication and electroencephalogram finding were associated with SPB (P < 0.05). In Spearman correlation analysis indicated that SPBS score were positively correlated with KSSE score (r = 0.510, P < 0.05) while negatively correlated with QOLIE-31 score (r = −0.506, P < 0.05). Multiple linear regression analysis revealed that factors such as KSSE, type of medication, residence and electroencephalogram finding accounted for 32.8% of the factors influencing SPB in adult epilepsy patients.Conclusion89.5% of adult epilepsy patients have varying degrees of SPB, which is associated with high stigma and poor quality of life. Therefore, during the treatment and nursing of adult epilepsy patients, clinical staff should pay attention to the psychological status of patients, help them reduce their psychological burden, and guide them to develop a healthy lifestyle.

The viral and inflammation hypothesis of epileptic seizures based on bioinformatic study of circulating miRNAs and peripheral whole-blood mRNAs of adult epilepsy patients.

BackgroundThe study aimed to investigate the genome-wide biological significance of the circulating miRNAs markers found in peripheral whole blood of adult epileptic seizures patients by integrating analysis using bioinformatics approaches.MethodsThe Gene Expression Omnibus (GEO) dataset was accessed to retrieve epilepsy-related circulating miRNA profile data (GSE114847) including 89 subjects (n = 40 epileptic and n = 49 healthy control), peripheral whole-blood mRNA expression data (GSE143772) including 64 subjects (n = 32 epileptic and n = 32 healthy control). To eliminate age disparities in epilepsy pathophysiology only adult epileptic patients were selected. Furthermore, GEO2R was used to identify adult-related mRNAs (AD-mRNAs) against epilepsy as potential biomarkers. Moreover, to predict the potential target genes for these mRNAs, we used mirWalk. Finally, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to investigate the biological activities of AD-mRNAs. Importantly, the protein–protein network of these identified AD-mRNAs was constructed. Eventually, the overlapping AD-mRNAs and AD-miRNAs and their functions were explored to shortlist potential AD-epileptic markers.ResultThe current study resulted in the identification of 79 upregulated and 40 downregulated different expression gene (DEGs) in both applied data. These targets were cross-linked and mapped with each other to acquire common adult epilepsy-related overlapped mRNAs (Mo-mRNAs). It was found that there was a total of 36 overlapping genes. These overlapped AD-mRNAs markers were found to be functionally enriched in cell regulating pathways i.e., positive regulation of type 1 interferon signaling pathway and mitochondrial cytochrome C release pathway, respectively.ConclusionThis research gives a comprehensive depiction of the mRNAs that may be involved in adult epilepsy patients' pathophysiological progressions.

Latent, Early or Late Human Herpes Virus-6B Expression in Adult Mesial Temporal Lobe Epilepsy: Association of Virus Life Cycle with Inflammatory Cytokines in Brain Tissue and Cerebral Spinal Fluid

Background: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. Methods: Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed. Results: Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups. Conclusions: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection.

Neuropilin-2 Signaling Modulates Mossy Fiber Sprouting by Regulating Axon Collateral Formation Through CRMP2 in a Rat Model of Epilepsy

Programmed neural circuit formation constitutes the foundation for normal brain functions. Axon guidance cues play crucial roles in neural circuit establishment during development. Whether or how they contribute to maintaining the stability of networks in mature brains is seldom studied. Upon injury, neural rewiring could happen in adulthood, of which mossy fiber sprouting (MFS) is a canonical example. Here, we uncovered a novel role of axon guidance molecule family Sema3F/Npn-2 signaling in MFS and epileptogenesis in a rat model of epilepsy. Dentate gyrus-specific Npn-2 knockdown increased seizure activity in epileptic animals along with increased MFS. Hippocampal culture results suggested that Npn-2 signaling modulates MFS via regulating axon outgrowth and collateral formation. In addition, we discovered that Sema3F/Npn-2 signal through CRMP2 by regulating its phosphorylation in the process of MFS. Our work illustrated that Npn-2 signaling in adult epilepsy animals could potentially modulate seizure activity by controlling MFS. MFS constitutes the structural basis for abnormal electric discharge of neurons and recurrent seizures. Therapies targeting Npn-2 signaling could potentially have disease-modifying anti-epileptogenesis effects in epilepsy treatment.

Anti-seizures therapeutics in patients with epilepsy: an approach to levetiracetam – review

Epilepsy is a chronic condition that consists of a transient disorder of brain function manifested by recurrent and unprovoked seizures affecting approximately 50 million people worldwide. Antiepileptic treatment is aimed at possible improvement the quality of life by reducing epilepsy seizures with the lowest possible side effects. One of the newest broad spectrum antiepileptic drug (AED) for the treatment of wide range of epilepsies – focal, partial, myoclonic, tonic-clonic and primary generalized seizures that can be used in both children and adults is levetiracetam. Levetiracetam is believed to bind to SV2A (synaptic vesicle protein 2A) in the brain, prevent the release of calcium stores from neurons and inhibit GABA and glycine activity. Due to the unique mechanism of action, high bioavailability (in both oral and intravenous administration), rapid absorption, metabolism based on the hydrolysis of acetamide groups in the blood (independent of the liver) and the lack of activity of the resulting metabolites, the drug is considered to be safe and effective in reducing and stopping seizures. In this review, we present the latest reports on the effectiveness of levetiracetam and its potential in the treatment of epilepsy in children and adults.

ATTCT and ATTCC repeat expansions in the ATXN10 gene affect disease penetrance of spinocerebellar ataxia type 10.

SummarySpinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant disorder caused by an expanded pentanucleotide repeat in the ATXN10 gene. This repeat expansion, when fully penetrant, has a size of 850–4,500 repeats. It has been shown that the repeat composition can be a modifier of disease, e.g., seizures. Here, we describe a Mexican kindred in which we identified both pure (ATTCT)n and mixed (ATTCT)n-(ATTCC)n expansions in the same family. We used amplification-free targeted sequencing and optical genome mapping to decipher the composition of these repeat expansions. We found a considerable degree of mosaicism of the repeat expansion. This mosaicism was confirmed in skin fibroblasts from individuals with ATXN10 expansions with RNAScope in situ hybridization. All affected family members with the mixed ATXN10 repeat expansion showed typical clinical signs of spinocerebellar ataxia and epilepsy. In contrast, individuals with the pure ATXN10 expansion present with Parkinson's disease or are unaffected, even in individuals more than 20 years older than the average age at onset for SCA10. Our findings suggest that the pure (ATTCT)n expansion is non-pathogenic, while repeat interruptions, e.g., (ATTCC)n, are necessary to cause SCA10. This mechanism has been recently described for several other repeat expansions including SCA31 (BEAN1), SCA37 (DAB1), and three loci for benign adult familial myoclonic epilepsy BAFME (SAMD12, TNRC6A, RAPGEF2). Therefore, long-read sequencing and optical genome mapping of the entire genomic structure of repeat expansions are critical for clinical practice and genetic counseling, as variations in the repeat can affect disease penetrance, symptoms, and disease trajectory.

Use of new intranasal benzodiazepines at a typical adult epilepsy center

ObjectiveThe aim of this study was to review out-of-hospital use of intranasal diazepam and midazolam for treatment of acute repetitive seizures (ARS) at a typical adult epilepsy center. MethodsData were collected through chart review and by telephone calls to either the patient or the caregiver regarding drug effectiveness, overall satisfaction, and adverse events. ResultsWe identified 96 patients who were prescribed either benzodiazepine. Thirty-nine patients in the diazepam group and 38 patients in the midazolam group were able to be contacted and were included in the study. Sixty-two percent of patients in the diazepam group and 55% of patients in the midazolam group had used the medication at the time of data collection. Of these patients, 83% of patients in the diazepam group and 85% of patients in the midazolam group reported cessation of seizures after either the first or second dose. In comparison of the average patient satisfaction between intranasal diazepam and midazolam, there was no statistical significance (4.25 ± 1.22 vs 3.95 ± 1.35; p = 0.42). Adverse events were minor, included fatigue, nasal discomfort, headache, and dizziness. DiscussionThe use of the two new intranasal benzodiazepines was roughly divided equally. Slightly more than half of the patients who were prescribed the medication had used it. The overall satisfaction of the two medications was comparable. These findings highlight the principal usability of intranasal diazepam and midazolam in adults with ARS.

Modelos experimentales en el estudio de la epileptogénesis

Epilepsy is a chronic neurological disease characterized by spontaneous recurrently occurring epileptic seizures as a consequence of abnormal, excessive and synchronous neuronal activity in the brain. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy in adults, being characterized by hippocampal sclerosis, reactive gliosis, neurodegeneration, and synaptic reorganization. Animal models of TLE based on the administration of convulsive agents trigger a status epilepticus (SE) that progresses towards the occurrence of spontaneous recurrent seizures. Among these models are those induced by the systemic administration of pilocarpine or by intrahippocampal injection of kainic acid, both being characterized by 3 clearly defined phases: (i) acute SE seizures; (ii) latent period and (iii) occurrence of recurrent spontaneous seizures. These models not only reproduce most of the neuropathological TLE features but also allow for the identification of biomarkers of epileptogenesis and potential pharmacological targets. The use of neuroimaging techniques such as positron emission tomography (PET) with the radiotracer 18F-Fluorodeoxyglucose (18F-FDG) identifies brain hypometabolism in the latent period that not only localizes the epileptic focus but is also an biomarker of early diagnosis. Other neuroimaging techniques allow for detecting, among others, biomarkers of neuroinflammation, alterations in the permeability of the blood-brain barrier and astrocytic activation, all of them associated with epileptogenesis. Finally, the use of chemogenetics through DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) technology in murine models leads to targeted modulation of astrocytic activity, being a novel tool that considers the contribution of the astrocytes role in brain metabolic alterations in epileptogenesis.

Vascular topology and blood flow are acutely impacted by experimental febrile status epilepticus

Febrile status epilepticus (FSE) is an important risk factor for temporal lobe epilepsy and early identification of those at high risk for epilepsy is vital. In a rat model of FSE, we identified an acute (2 hrs) novel MRI signal where reduced T2 relaxation values in the basolateral amygdala (BLA) predicted epilepsy in adulthood; this T2 signal remains incompletely understood and we hypothesized that it may be influenced by vascular topology. Experimental FSE induced in rat pups reduced blood vessel density of the cortical vasculature in a lateralized manner at 2 hrs post FSE. Middle cerebral artery (MCA) exhibited abnormal topology in FSE pups but not in controls. In the BLA, significant vessel junction reductions and decreased vessel diameter were observed, together with a strong trend for reduced vessel length. Perfusion weighted MRI (PWI) was acutely increased cerebral blood flow (CBF) in cortex, amygdala and hippocampus of FSE pups that correlated to decreased T2 relaxation values compared to controls. This is consistent with increased levels of deoxyhemoglobin associated with increased metabolic demand. In summary, FSE acutely modifies vascular topological and CBF in cortex and BLA that may underlie acute MRI signal changes that predict progression to future epilepsy.

Updated guideline on diagnosing and managing epilepsies

NICE has recently updated its guideline on diagnosing and managing epilepsies in children, young people and adults (NG217). This article provides a brief summary of the new guidance, which provides detailed recommendations on assessment, referral and management of different epilepsy and seizure types.

Clinical characteristics of cognitive impairment and its related risk factors in post-stroke epilepsy

Post-stroke epilepsy (PSE) patients are prone to cognitive impairment (CI) due to multiple factors. This study aimed to assess clinical characteristics of CI and its related risk factors in newly diagnosed Chinese Han adult epilepsy patients with ischaemic stroke. Data were collected on PSE patients hospitalized in the neurology ward of the Affiliated Hospital of Yangzhou University, from January 2016 to May 2019. Newly diagnosed PSE patients were followed for six months; their cognitive functions were then assessed according to the Chinese Beijing version of the Montreal Scale (MoCA) and patients were divided into a PSE+CI group (MoCA scale score <26) (n=81) or PSE-CI group (MoCA scale score ≥26) (n=36). Data collection tools also included the Chinese versions of the Zheng Self-assessment Anxiety Scale, the Zheng Self-assessment Depression Scale, the Barthel index and the National Hospital Seizure Severity Scale. We compared the basic clinical characteristics between the two groups of patients and investigated the factors of CI in PSE patients. In total, CI was present in 81 (69%) and absent in 36 (31%) PSE patients. MoCA total score in the PSE+CI group was 20.85±4.13 and 27.53±1.34 in the PSECI group. The Bonferroni corrected significance level was 0.0013. Scores for multiple cognitive domains (visuospatial/executive skills, naming, attention, language and delayed recall) were lower in the PSE+CI group than the PSE-CI group. Moreover, the PSE+CI group had a higher incidence of depression and anxiety. Univariate analysis showed that diabetes (p= 0.000) and the number of antiepileptic drugs (AEDs) (p= 0.001) were associated with CI in PSE. Binary logistic regression analysis showed that diabetes (odds ratio [OR]: 5.242, 95% confidence interval [CI]: 1.680-16.363, p= 0.004), high homocysteine levels (OR: 1.103, 95% CI: 1.008-1.207, p= 0.033) and the number of AEDs (OR: 3.354, 95% CI: 1.225-9.180, p= 0.019) were associated with CI in PSE. Diabetes, high homocysteine levels and a higher number of AEDs may be risk factors for CI in PSE.

Transition from pediatric to adult care among patients with epilepsy: Cross-sectional surveys of experts and patients in Korea.

ObjectivesMany pediatric patients with epilepsy require treatment beyond the pediatric age. These patients require transition to an adult epilepsy center. Currently, many centers worldwide run epilepsy transition programs. However, a standardized protocol does not exist in Korea. The basic data required to establish a transition program are also unavailable. We aimed to assess the status and perceptions of patients and epilepsy care providers on transition.MethodsTo assess the status of epilepsy transition, we retrospectively collected data from patients with epilepsy older than 18 years who visited our pediatric epilepsy clinic between March 1990 and July 2019. To assess the perception of transition, we surveyed patients, parents, pediatric neurologists (PN), and adult epileptologists (AE).ResultsIn a retrospective chart review, 39 of 267 (14.6%) patients visited the adult epilepsy clinic after consulting a pediatric neurologist, and three patients returned to the pediatric center. The average patient age at transition was 23.29 ± 5.10 years. A total of 94 patients or their guardians and 100 experts participated in the survey. About half of the patients or guardians (44.7%) did not want to transition and emotional dependence was the commonest reason. Most patients (52.1%) thought that the appropriate age of transition was above 20 years. PNs had greater concerns about patients' compliance than AEs. Regarding the age of transition, AEs believed that a younger age (18 years) was more appropriate than PNs (20 years).SignificanceThis study describes difficulties in the transition from pediatric to adult epilepsy centers without appropriate support. There were differences in perspectives among patients, parents, and adult and pediatric epilepsy care providers. This study can assist in creating a standardized protocol in Korea.

Adjunctive Transdermal Cannabidiol for Adults With Focal Epilepsy

Cannabidiol has shown efficacy in randomized clinical trials for drug-resistant epilepsy in specific syndromes that predominantly affect children. However, high-level evidence for the efficacy and safety of cannabidiol in the most common form of drug-resistant epilepsy in adults, focal epilepsy, is lacking. To investigate the efficacy, safety, and tolerability of transdermally administered cannabidiol in adults with drug-resistant focal epilepsy. A randomized, double-blind, placebo-controlled, multicenter clinical trial at 14 epilepsy trial centers in Australia and New Zealand. Participants were adults with drug-resistant focal epilepsy receiving a stable regimen of up to 3 antiseizure medications. Data were analyzed from July 2017 to November 2018. Eligible participants were randomized (1:1:1) to 195-mg or 390-mg transdermal cannabidiol or placebo twice daily for 12 weeks, after which they could enroll in an open-label extension study for up to 2 years. Seizure frequency was self-reported using a daily diary. The primary efficacy end point was the least squares mean difference in the log-transformed total seizure frequency per 28-day period, adjusted to a common baseline log seizure rate, during the 12-week treatment period. A total of 188 patients (45% male [85 patients] and 54.8% female [103 patients]) with a mean (SD) age of 39.2 (12.78) years were randomized, treated, and analyzed (195-mg cannabidiol, 63 participants; 390-mg cannabidiol, 62 participants; placebo, 63 participants). At week 12 of the double-blind period, there was no difference in seizure frequency between placebo (mean [SD] 2.49 [1.31] seizures per 28 days) and 195-mg cannabidiol (mean [SD] 2.51 [1.15] seizures per 28 days; least squares mean difference, 0.014; 95% CI, -0.175 to 0.203; P = .89) or 390-mg cannabidiol (mean [SD] 2.59 [1.12] seizures per 28 days; least squares mean difference, 0.096; 95% CI, -0.093 to 0.285; P = .32). By month 6 of the open-label extension, 115 patients (60.8%) achieved a seizure reduction of at least 50%. Treatment-emergent adverse events occurred in 50.4% (63 of 125 participants) of the cannabidiol group vs 41.3% (26 of 63 participants) in the placebo group, with a treatment difference of 9.1% (95% CI, -6.0% to 23.6%), and occurred at similar rates in the cannabidiol groups. Few participants discontinued (7% [14 of 188 participants]), and most (98% [171 of 174 participants]) continued into the open-label extension. Both doses of transdermal cannabidiol were well tolerated and safe. No significant difference in efficacy was observed between cannabidiol and placebo during the double-blind treatment period. The open-label extension demonstrated the long-term safety, tolerability, and acceptability of transdermal cannabidiol delivery. ACTRN12616000510448 (double-blind); ACTRN12616001455459 (open-label).

Multimodal Presurgical Evaluation of Medically Refractory Focal Epilepsy in Adults: An Update for Radiologists.

Surgery is a potentially curative treatment option for patients with medically refractory focal epilepsy. Advanced neuroimaging modalities often improve surgical outcomes by contributing key information during the highly individualized surgical planning process and intraoperative localization. Hence, neuroradiologists play an integral role in the multidisciplinary management team. In this review, we initially present the conceptual background and practical framework of the presurgical evaluation process, including a description of the surgical treatment approaches used for medically refractory focal epilepsy in adults. This background is followed by an overview of the advanced modalities commonly used during the presurgical workup at level IV epilepsy centers, including diffusion imaging techniques, blood oxygenation level-dependent functional MRI (fMRI), PET, SPECT, and subtraction ictal SPECT, and by introductions to 7-T MRI and electrophysiologic techniques including electroencephalography and magnetoencephalography. We also provide illustrative case examples of multimodal neuroimaging including PET/MRI, PET/MRI-diffusion-tensor imaging (DTI), subtraction ictal SPECT, and image-guided stereotactic planning with fMRI-DTI.

Expression Profile of Immunoglobulin G Glycosylation in Children With Epilepsy in Han Nationality.

BackgroundEpilepsy is a chronic brain disease that recurs during childhood, and more than half of adult epilepsy originates from childhood. Studies suggested that immunoglobulin G (IgG) glycosylation are closely related to neurological diseases. Here we analyzed the characteristics of the immunoglobulin glycosylation profile of children with epilepsy.MethodsPatients were recruited in Taian, Shandong Province from December 2019 to March 2020. Serum IgG glycome composition was analyzed by hydrophilic interaction liquid chromatography with ultra-high-performance liquid chromatography approach.ResultsThe proportion of fucosylated glycans in total IgG glycans was 93.72% in the epilepsy patients, which was significantly lower than that in the control group (94.94%). A lower level of total monogalactosylated and digalactosylated glycans were observed in the epilepsy patients group (30.76 and 40.14%) than that in the controls (36.17 and 42.69%). There was no significant difference between the two groups in bisected GlcNAc glycans and sialylated glycans.ConclusionThe decrease of core fucosylation and galactosylation may promote the inflammatory reaction of the body and participate in the occurrence of epilepsy in children.