The first ER-targeting flavone-based fluorescent probe for Cys: Applications in real-time tracking in an epilepsy model and food analysis.

Epilepsy is one of the most commonly-seen neurological disorders, and both endoplasmic reticulum stress (ERS) and oxidative stress (OS) have been demonstrated to be associated with epileptic seizures. As one of the three endogenous thiol-containing amino acids, cysteine (Cys) is recognized not only as an important biomarker of various biological processes but also widely used as a significant additive in the food industry. However, the exact role that Cys plays in ERS has not been well answered up to now. In this paper, we reported the first flavone-based fluorescent probe (namely BFC) with nice endoplasmic reticulum (ER)-targeting ability, which was capable of monitoring Cys in a fast response (3.0 min), large stokes shift (130 nm) and low detection limit (10.4 nM). The recognition mechanism of Cys could be attributed to the addition-cyclization reaction involving a Cys residue and an acrylate group, resulting in the release of the strong excited-state intramolecular proton transfer (ESIPT) emission molecule of benzoflavonol (BF). The low cytotoxicity and good biocompatibility of the probe BFC allowed for monitoring the fluctuation of endogenous Cys levels under both ERS and OS processes, as well as in zebrafish models of epilepsy. Quantitative determination of Cys with the probe BFC was also achieved in three different food samples. Additionally, a probe-immersed test strips integrated with a smartphone device was successfully constructed for on-site colorimetric detection of Cys. Undoubtedly, our work provided a valuable tool for tracking Cys levels in both an epilepsy model and real food samples.

SCN1A intronic variants impact on Nav1.1 protein expression and sodium channel function, and associated with epilepsy phenotypic severity.

High-throughput sequencing has identified numerous intronic variants in the SCN1A gene in epilepsy patients. Abnormal mRNA splicing caused by these variants can lead to significant phenotypic differences, but the mechanisms of epileptogenicity and phenotypic differences remain unknown. Two variants, c.4853-1 G>C and c.4853-25 T>A, were identified in intron 25 of SCN1A, which were associated with severe Dravet syndrome (DS) and mild focal epilepsy with febrile seizures plus (FEFS+), respectively. The impact of these variants on protein expression, electrophysiological properties of sodium channels and their correlation with epilepsy severity was investigated through plasmid construction and transfection based on the aberrant spliced mRNA. We found that the expression of truncated mutant proteins was significantly reduced on the cell membrane, and retained in the cytoplasmic endoplasmic reticulum. The mutants caused a decrease in current density, voltage sensitivity, and an increased vulnerability of channel, leading to a partial impairment of sodium channel function. Notably, the expression of DS-related mutant protein on the cell membrane was higher compared to that of FEFS+-related mutant, whereas the sodium channel function impairment caused by DS-related mutant was comparatively milder than that caused by FEFS+-related mutant. Our study suggests that differences in protein expression levels and altered electrophysiological properties of sodium channels play important roles in the manifestation of diverse epileptic phenotypes. The presence of intronic splice site variants may result in severe phenotypes due to the dominant-negative effects, whereas non-canonical splice site variants leading to haploinsufficiency could potentially cause milder phenotypes.

Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype.

BACKGROUND: Chromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty. RESULTS: We identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene. CONCLUSION: This report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

Clinical characteristics and post-operative outcomes in children with malformation of cortical development related drug-resistant epilepsy: 428 cases in one pediatric epilepsy center.

AIMS: To investigate post-operative seizure outcomes, and predictors of surgical outcomes of the malformation of cortical development (MCD) in children with drug-resistant epilepsy (DRE) and age-specific characteristics. METHODS: We retrospectively analyzed clinical data from 428 children with MCD-related DRE who underwent curative surgical treatment. Statistical analyses were conducted to identify correlative characteristics, prognostic predictors, and differences among various age groups. RESULTS: After more than 3 years of follow-up, 81.3% of patients achieved Engel I outcomes. Prognosis was correlated with factors such as age at surgery, MRI findings, invasive EEG, pathology, acute postoperative seizures (APOS), and the number of preoperative and postoperative anti-seizure medications (AEDs). Age at surgery and the number of preoperative AEDs (p < 0.001) were significant predictors of seizure recurrence. Distinct clinical characteristics were observed among different age groups. CONCLUSION: Surgery is effective in terminating MCD-related DRE. Younger age at surgery and fewer preoperative AEDs are associated with better prognoses. Clinical characteristics vary significantly with age.

Global, regional, and national time trends in the burden of epilepsy, 1990-2019: an age-period-cohort analysis for the global burden of disease 2019 study.

Background: Epilepsy is a non-communicable chronic brain disease that affects all age groups. There are approximately 50 million epilepsy patients worldwide, which is one of the most common neurological disorder. This study reports the time trends in the burden of epilepsy from 1999 to 2019. Methods: We evaluated the disease burden and its temporal trends of epilepsy using the prevalence and years lived with disability (YLDs), which was estimated based on the Global Burden of Disease (GBD) 2019 study. The age-period-cohort (APC) model was used to estimate the temporal trends of the epilepsy prevalence and YLDs rates, and to analyze the relative risks of age, periods and queues (age/period/queue effects). Results: In the past 30 years, the global age-standardized prevalence rate and age-standardized rate has increased by 29.61% and 27.02%, respectively. Globally, the APC model estimated the net drift of prevalence and YLDs were 0.88% (95% CI: 0.83-0.93) and 0.80% (95% CI: 0.75-0.85) per year. Among 204 countries and territories, the YLDs in 146 and prevalence 164 showed an increasing trend. And the risk of YLDs and prevalence increases with age, with the lowest risk among 0-4 years old and the highest risk among 75-79 years old. Unfavorable increasing period and cohort risks of YLDs and prevalence were observed. Conclusion: Over the past 30 years, the YLDs and prevalence of epilepsy have gradually increased globally and unfavorable increasing period and cohort risks were observed. Emphasizing epilepsy prevention, strengthening epilepsy health education, optimizing older adults epilepsy diagnosis and treatment plans, and actively promoting epilepsy diagnosis and treatment plans can effectively reduce new cases of epilepsy and related disabilities.

The Most Frequent Psychiatric Comorbidities in Bulgarian Patients With Epilepsy: Their Connection With the Main Clinical Characteristics and Quality of Life.

AIM:  The objective of this study is to determine and compare the relationship of the most common psychiatric comorbidities in Bulgarian patients with epilepsy with the main clinical characteristics, as well as to evaluate their impact on certain aspects of the quality of life. CLINICAL RATIONALE:  Psychiatric comorbidities occur in about one-third of people with epilepsy throughout their lifetime, and their incidence is much greater in high-risk groups such as patients with treatment-resistant epilepsy. MATERIAL AND METHODS:  The study group consisted of 129 participants, of whom 104 were divided into four groups according to the presence of one of the most frequently diagnosed psychiatric comorbidities in our patients with epilepsy: personality and behavioral disorder (PBD) (n=25), mild to moderate depressive disorder (n=26), anxiety disorder (n=32), and dissociative and conversion disorders (n=21). A control group was also formed with a similar number of participants with epilepsy (n=25) without psychiatric comorbidity. Some sociodemographic and clinical characteristics of epilepsy were analyzed in all patients. All patients filled out two questionnaires: the Bulgarian version of quality of life in epilepsy - 89 (QOLIE-89) and the Bulgarian version of SIDAED (assessing SIDe effects in antiepileptic drugs (AED) treatment). RESULTS:  The analysis revealed a negative influence of psychiatric comorbidity on the presence of epileptic seizures, unwanted drug effects, and lower scores for all aspects of the quality of life of patients with epilepsy. CONCLUSION AND CLINICAL IMPLICATIONS:  The main conclusion of our study is the presence of an interaction between psychiatric comorbidity, the clinical course of the disease, and the deteriorated quality of life (QOL) in patients with epilepsy. Further attention, comprehensive care, and targeted research are needed to analyze individual psychiatric comorbidities in patients with epilepsy for early detection and treatment.

A Review of EEG-based Localization of Epileptic Seizure Foci: Common Points with Multimodal Fusion of Brain Data.

Unexpected seizures significantly decrease the quality of life in epileptic patients. Seizure attacks are caused by hyperexcitability and anatomical lesions of special regions of the brain, and cognitive impairments and memory deficits are their most common concomitant effects. In addition to seizure reduction treatments, medical rehabilitation involving brain-computer interfaces and neurofeedback can improve cognition and quality of life in patients with focal epilepsy in most cases, in particular when resective epilepsy surgery has been considered treatment in drug-resistant epilepsy. Source estimation and precise localization of epileptic foci can improve such rehabilitation and treatment. Electroencephalography (EEG) monitoring and multimodal noninvasive neuroimaging techniques such as ictal/interictal single-photon emission computerized tomography (SPECT) imaging and structural magnetic resonance imaging are common practices for the localization of epileptic foci and have been studied in several kinds of researches. In this article, we review the most recent research on EEG-based localization of seizure foci and discuss various methods, their advantages, limitations, and challenges with a focus on model-based data processing and machine learning algorithms. In addition, we survey whether combined analysis of EEG monitoring and neuroimaging techniques, which is known as multimodal brain data fusion, can potentially increase the precision of the seizure foci localization. To this end, we further review and summarize the key parameters and challenges of processing, fusion, and analysis of multiple source data, in the framework of model-based signal processing, for the development of a multimodal brain data analyzing system. This article has the potential to be used as a valuable resource for neuroscience researchers for the development of EEG-based rehabilitation systems based on multimodal data analysis related to focal epilepsy.

Stopping runaway seizures with a chill pill.

The neuropeptide neurotensin can reduce status epilepticus and its associated consequences through induction of therapeutic hypothermia when bound to a molecule that can penetrate the blood-brain barrier.

Review: seizure-related consolidation and the network theory of epilepsy.

Epilepsy is a complex, multifaceted disease that affects patients in several ways in addition to seizures, including psychological, social, and quality of life issues, but epilepsy is also known to interact with sleep. Seizures often occur at the boundary between sleep and wake, patients with epilepsy often experience disrupted sleep, and the rate of inter-ictal epileptiform discharges increases during non-REM sleep. The Network Theory of Epilepsy did not address a role for sleep, but recent emphasis on the interaction between epilepsy and sleep suggests that post-seizure sleep may also be involved in the process by which seizures arise and become more severe with time ("epileptogenesis") by co-opting processes related to the formation of long-term memories. While it is generally acknowledged that recurrent seizures arise from the aberrant function of neural circuits, it is possible that the progression of epilepsy is aided by normal, physiological function of neural circuits during sleep that are driven by pathological signals. Studies recording multiple, single neurons prior to spontaneous seizures have shown that neural assemblies activated prior to the start of seizures were reactivated during post-seizure sleep, similar to the reactivation of behavioral neural assemblies, which is thought to be involved in the formation of long-term memories, a process known as Memory Consolidation. The reactivation of seizure-related neural assemblies during sleep was thus described as being a component of Seizure-Related Consolidation (SRC). These results further suggest that SRC may viewed as a network-related aspect of epilepsy, even in those seizures that have anatomically restricted neuroanatomical origins. As suggested by the Network Theory of Epilepsy as a means of interfering with ictogenesis, therapies that interfered with SRC may provide some anti-epileptogenic therapeutic benefit, even if the interference targeted structures that were not involved originally in the seizure. Here, we show how the Network Theory of Epilepsy can be expanded to include neural plasticity mechanisms associated with learning by providing an overview of Memory Consolidation, the mechanisms thought to underlie MC, their relation to Seizure-Related Consolidation, and suggesting novel, anti-epileptogenic therapies targeting interference with network activation in epilepsy following seizures during post-seizure sleep.

Quality of life in SCN1A-related seizure disorders across the lifespan.

This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other SCN1A-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a SCN1A-related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [ß = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (ß = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (ß = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, P < 0.05), mediated by a lower prevalence of behavioural problems (ß = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (ß = -0.1, 95%CI (-0.2 to -0.0)) and older age (ß = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.

Intracerebral delivery of antiseizure medications by microinvasive neural implants.

Focal epilepsy is a difficult disease to treat as two-thirds of patients will not respond to oral antiseizure medications (ASMs) or have severe off-target effects that lead to drug discontinuation. Current non-pharmaceutical treatment methods (resection or ablation) are underutilized due to the associated morbidities, invasive nature, and inaccessibility of seizure foci. Less invasive non-ablative modalities may potentially offer an alternative. Targeting the seizure focus in this way may avoid unassociated critical brain structures to preserve function and alleviate seizure burden. Here we report use of an implantable, miniaturized neural drug delivery system [Microinvasive neural implant infusion platform (MINI)] to administer antiseizure medications (ASMs) directly to the seizure focus in a mouse model of temporal lobe epilepsy. We examined the effect local delivery of phenobarbital (PB) and valproate (VPA) had on focal seizures, as well as adverse effects, and compared this to systemic delivery. We show that local delivery of PB and VPA using our chronic implants significantly reduced focal seizures at all doses given. Furthermore, we show that local delivery of these compounds resulted in no adverse effects to motor function, whereas systemic delivery resulted in significant motor impairment. The results of this study demonstrate the potential of ASM micro dosing to the epileptic focus as a treatment option for people with drug resistant epilepsy. This technology could also be applied to a variety of disease states, enabling a deeper understanding of focal drug delivery in the treatment of neurological disorders.

The relationship between seizure self-efficacy and quality of life in children with epilepsy.

AIM: This study aimed to examine seizure self-efficacy and quality of life of children with epilepsy and to evaluate the relationship between these parameters. METHOD: The study was conducted between November 2022 and November 2023 in the Pediatric Neurology Outpatient Clinic of a university hospital with 200 children aged 9-14 who met the inclusion criteria and accepted the study. The data were collected using the "Child Descriptive Form," "Seizure Self-Efficacy Scale in Children with Epilepsy," and "KIDSCREEN-27 Health-Related Quality of Life Scale". The data were evaluated using the IBM SPSS Statistics Standard Concurrent User V 26 statistical package program. Number, percentage, mean-standard deviation, median, minimum and maximum values, Cronbach's Alpha coefficient, Shapiro Wilk normality test, Independent Sample t-test, Analysis of Variance (ANOVA), Bonferroni test, Pearson correlation coefficient, linear regression analysis, Durbin-Watson value and normality of residuals Q-Q graphs were used in the evaluation of the data. A value of p < 0.05 was considered statistically significant. RESULTS: It was determined that 53 % of the children participating in the study were male, and the median age was 12 years. The mean total score of the seizure self-efficacy scale was 3.13 ± 1.03, and the mean total score of the health-related quality of life scale was 89.83 ± 15.63. There was a statistically significant positive correlation between the dimension of individual seizure control and total score of health-related quality of life and physical well-being, emotional well-being and social support, and peer dimensions (p < 0.05). A statistically significant positive correlation was determined between the effect of environment on seizure control and health-related quality of life total score, physical well-being, social support, and peer and school environment dimensions (p < 0.05). A statistically significant positive correlation was determined between seizure self-efficacy total score and health-related quality of life total score and physical well-being, emotional well-being, social support, and peer dimensions (p < 0.05). CONCLUSION: The study results reveal that high self-efficacy levels of children with epilepsy improve the quality of life of children with epilepsy.

Preclinical toxicity studies supporting 2DG for treatment of status epilepticus.

2-deoxy-D-glucose (2DG) has been proposed as a potential antiseizure treatment based on seizure suppressive actions in multiple acute and chronic seizure models, including models of status epilepticus (SE). Here we summarize recently completed preclinical toxicological studies of single doses of an intravenous formulation of 2DG supporting potential safety of 2DG for acute treatment of SE and acute repetitive seizures (ARS).

Quantitative phenotyping of verbal and non-verbal cognitive impairment using diffusion-weighted MRI connectome: Preliminary study of the crowding effect in children with left hemispheric epilepsy.

The "crowding" effect (CE), wherein verbal functions are preserved presumably at the expense of nonverbal functions, which diminish following inter-hemispheric transfer of language functions, is recognized as a specific aspect of functional reorganization, offering an insight about neural plasticity in children with neural insult to the dominant hemisphere. CE is hypothesized as a marker for language preservation or improvement after left-hemispheric injury, yet it remains challenging to fully discern it in preoperative evaluation. We present a novel DWI connectome (DWIC) approach to predict the presence of CE in 24 drug-resistant epilepsy (DRE) patients with a left-hemispheric focus and 29 young healthy controls. Psychometry-driven DWIC analysis was applied to create verbal and non-verbal modular networks. Local efficiency (LE) was assessed at individual regions of the two networks and its Z-score was compared to predict the presence of CE. Compared with a traditional organization (TO) group, wherein verbal functions are adversely affected, while non-verbal functions are preserved, the CE group showed significantly higher Z-scores in verbal network and significantly lower Z-scores in non-verbal network, corresponding to network reorganization in CE. A larger number of antiseizure drugs was significantly associated with more decreased Z-score in the right non-verbal network of the CE group and left verbal network of the TO group. These findings hold great potential to identify DRE patients whose verbal/language skills may over time be preserved due to effective inter-hemispheric reorganization and identify those whose verbal/language impairments may persist due to lack of inter-hemispheric reorganization.

Communication trends over time in new-onset refractory status epilepticus (NORSE): Interim analysis from the NORSE/FIRES Family Registry.

The new-onset refractory status epilepticus (NORSE)/febrile infection-related epilepsy syndrome (FIRES) Family Registry contributes to a systematic effort to collect clinical and epidemiological information on individuals affected by NORSE/FIRES. We explore diagnostic and prognostic information provided to patients and their families, their satisfaction with the communication, and utilisation of palliative care services during acute hospitalization. Communication about the diagnosis of NORSE/FIRES to families has improved since the publication of consensus definitions in 2018, with families being more likely to be told about NORSE/FIRES after 2018. Families rate the quality of prognostic information as being moderate. Palliative care services were involved in a minority of patients. Understanding and characterizing the prevalence and satisfaction of diagnostic and prognostic conversations is important for improving overall care, the quality of physician-patient-family relationships, and the recovery process for those affected by NORSE/FIRES.

Unusual cause for seizure after surgical closure of CSF rhinorrhoea.

Seizure following cerebrospinal fluid (CSF) rhinorrhoea surgery or surgery of the skull base almost always implies postoperative meningoencephalitis, unless proven otherwise. Here, we present the case of a middle-aged female in her 40's who underwent surgical CSF fistula closure and developed seizure on the eighth postoperative day. She was diagnosed to have posterior reversible encephalopathy syndrome (PRES). Early diagnosis and prompt initiation of treatment ensured that she had a complete recovery. Although not reported in the literature, PRES should always be a differential diagnosis in such situations, as delay in diagnosis may result in significant morbidity and rarely mortality.

Hippocampal resection during hemispherotomy: is it needed?

PURPOSE: Hemispherotomy is an effective surgery for intractable pediatric hemispheric epilepsy. Over the years, the surgical goal has shifted from a complete hemispheric resection (anatomical hemispherectomy) to a disconnective hemispherotomy (DH). Multiple techniques for DH have been described, and often, anterior temporal lobectomy (ATL, with hippocampal resection) is performed. The goal of the current study is to assess the role of hippocampal resection in DH. METHODS: We retrospectively collected all clinical data of children (< 18 years old) who underwent DH between 2001 and 2022 at two tertiary large centers. Epilepsy status and surgical outcome were compared, based on whether the hippocampus was resected (as part of an ATL) or disconnected at the amygdala and atrial segment of the fornix (with no ATL). RESULTS: A total of 86 patients (32 females) were included. The most common epilepsy etiologies were stroke (31), Rasmussen's encephalitis (16), cortical dysplasia (10), and hemimegaloencephaly (9). The mean age at surgery was 7 (± 4.9) years. The average number of anti-seizure medications (ASMs) at surgery was 3 (± 1.2). Hemispherotomy techniques included peri-insular (54), vertical (23 [19 endoscopic + 4 parasagittal]), and trans-sylvian (9). The mean follow-up was 41.5 (± 38) months. Forty-three patients had hippocampal resection, and 43 patients had a hippocampal disconnection. Both groups had similar Engel outcome scores (p = 0.53). CONCLUSIONS: Disconnective hemispherotomy is highly effective for pediatric intractable hemispheric epilepsy. Our data suggest that the inclusion of hippocampal resection does not provide additional benefit.

A roadmap for SHANK3-related Epilepsy Research: recommendations from the 2023 strategic planning workshop.

On September 27, 2023, the CureSHANK nonprofit foundation sponsored a conference in Boston, Massachusetts, to identify gaps in knowledge surrounding SHANK3-related epilepsy with the goal of determining future research priorities and recommendations. In addition to patient families and members of the CureSHANK community, participants in the conference included a broad cross-section of preclinical and clinical researchers and clinicians with expertise in SHANK3-related epilepsy as well as representatives from the pharmaceutical industry. Here we summarize the outcomes from comprehensive premeeting deliberations and the final conference recommendations, including (1) gaps in knowledge related to clinical science, (2) gaps in knowledge related to preclinical science, and (3) research priorities moving forward.

A roadmap for SHANK3-related Epilepsy Research: recommendations from the 2023 strategic planning workshop Phelan-McDermid Syndrome, a rare genetic disorder linked to the SHANK3 gene, manifests in a spectrum of clinical phenotypes including intellectual disability, autism spectrum disorder, and epilepsy. Epilepsy has been particularly under-investigated in this syndrome, and most of the animal models studied to date do not display seizures. On September 27, 2023, the CureSHANK nonprofit foundation sponsored a conference in Boston, Massachusetts, to identity gaps in knowledge surrounding SHANK3-related epilepsy. Conference attendees included patient families, basic scientists, clinical researchers, clinicians and representatives from the pharmaceutical industry with interest in SHANK3-related epilepsy. This review summarizes the outcome of this conference, including a summary of current state of knowledge and resources available, gaps in our understanding, priorities for future research in this important manifestation of PMS.

Clinical correlates of perceived stigma among people living with epilepsy enrolled in a self-management clinical trial.

BACKGROUND AND PURPOSE: Stigma is a pervasive barrier for people living with epilepsy (PLWE) and can have substantial negative effects. This study evaluated clinical correlates of perceived stigma in a research sample of PLWE considered to be at high risk due to frequent seizures or other negative health events. METHODS: Analyses were derived from baseline data from an ongoing Centers for Disease Control and Prevention (CDC)-funded randomized controlled trial (RCT) testing an epilepsy self-management approach. Standardized measures assessed socio-demographics, perceived epilepsy stigma, epilepsy-related self-efficacy, epilepsy self-management competency, health literacy, depressive symptom severity, functional status, social support and epilepsy-related quality of life. RESULTS: There were 160 individuals, mean age of 39.4, (Standard deviation/SD=12.2) enrolled in the RCT, 107 (66.9 %) women, with a mean age of epilepsy onset of 23.9 (SD 14.0) years. The mean seizure frequency in the prior 30 days was 6.4 (SD 21.2). Individual factors correlated with worse perceived stigma were not being married or cohabiting with someone (p = 0.016), lower social support (p < 0.0001), lower self-efficacy (p < 0.0001), and lower functional status for both physical health (p = 0.018) and mental health (p < 0.0001). Perceived stigma was associated with worse depressive symptom severity (p < 0.0001). Multivariable linear regression found significant independent associations between stigma and lower self-efficacy (ß -0.05; p = 0.0096), lower social support (ß -0.27; p = 2.4x10-5, and greater depression severity (ß 0.6; p = 5.8x10-5). CONCLUSIONS: Perceived epilepsy stigma was positively correlated with depression severity and negatively correlated with social support and self-efficacy. Providers caring for PLWE may help reduce epilepsy stigma by screening for and treating depression, encouraging supportive social relationships, and providing epilepsy self-management support. Awareness of epilepsy stigma and associated factors may help reduce some of the hidden burden borne by PLWE.

Temporal PLGG and epilepsy.

Temporal lobe epilepsy in children is often secondary to various low-grade glial and glioneural tumors and rarely secondary to mesial temporal sclerosis. Despite the benign nature, tumor-associated TLE in children often becomes refractory over time. Abundant literature has shown the significant advantage of tumor resection compared to conservative treatment, in achieving seizure control, as well as the rates of antiseizure medication reduction. Despite these advantages, several considerations are to be related to when considering surgery. These include the impact of surgery on linguistic and neurocognitive development, especially at the younger age; the extent of resection and the role of ECoG; and the need for mesial temporal resection. Over recent years, traditional resection has been complemented with newer treatment options such as laser ablation and biological treatment, and these should be taken into account depending on the exact location and the ability to perform extensive resection in eloquent regions. In this overview manuscript, we discuss the various considerations treating tumor-associated pediatric temporal epilepsy.