Epilepsies are complex neurological entities usually co-existing with neuropsychiatric comorbidities. We already demonstrated that microinjection of oxytocin (OT) into the central nucleus of amygdala (CeA) induces hypergrooming in Wistar rats, a model of compulsion. Furthermore, the Wistar Audiogenic Rat (WAR) strain is a genetic model of generalized tonic-clonic seizures. Here we quantified grooming behavior in WAR, with grooming scores, flowcharts and directed graphs of syntactic and non-syntactic grooming chains, after bilateral administration of OT or saline (SAL) into the CeA. Our current pioneer behavioral description considers that hypergrooming (compulsion) in WARs is a comorbidity because: (1) WARs have the highest grooming scores, when exposed only to novelty (2), WARs have better grooming scores than Wistars after CeA-SAL, (3) Epileptic WARs perform much better than Wistars in OT-CeA-dependent stereotyped behavioral sequences (flowcharts of syntactic/non-syntactic grooming chains). One additional observation is that the behavioral sequences here demonstrated can be modeled as reliable Markov chains. In conclusion we can drive hypergrooming in WARs, defined previously as a model of ritualistic motor behavior in Wistar rats, with OT from CeA, one of the principal amygdala complex outputs. As perspectives, ongoing cellular studies are on their way, to demonstrate the neural network, certainly incorporating cortico-striatal-thalamic-basal ganglia-cortical circuits, driven from CeA OT-dependent grooming pattern, a stereotyped, sequential and complex array of behaviors, and its association with seizure susceptibility.

Late-onset epilepsy (LOE) usually refers to the development of epilepsy at the age of 50 years or older. Approximately 20 % of LOE cases are diagnosed as late-onset epilepsy of unknown etiology (LOUE) due to a lack of an identifiable cause. The aim of this study was to investigate the clinical features, seizure and cognitive outcomes of patients with LOUE in West China.

To investigate the impact of epilepsy surgery on the developmental outcome in infancy with pharmacoresistant epilepsy and its associated factors.

Temporal lobe epilepsy is often accompanied by comorbid symptoms such as anxiety, depression, and cognitive dysfunction. Research indicates a close relationship between blood-brain barrier (BBB) impairment and these symptoms. DL-3n-butylphthalide (NBP) has been reported to protect the BBB, but the molecular mechanisms by which NBP protects the BBB in epilepsy models remain unclear. This study investigated the protective effects of NBP on the BBB in epileptic mice to alleviate the comorbid symptoms associated with epilepsy.

This narrative review aims to identify and summarize existing research to better understand the pathophysiological and neuroanatomical bases of social cognition deficits in people with epilepsy. The neuroanatomical basis of social cognition was primarily examined in healthy subjects. In healthy individuals, social cognition is supported by a complex network of interconnected brain regions. Facial emotion recognition relies on a distributed set of structures, including the occipitotemporal neocortex, the temporoparietal and prefrontal areas, and the putamen with a pivotal role of the amygdala. Theory of mind primarily involves the dorsal medial prefrontal cortex and temporoparietal junction, while empathy engages the anterior insular and cingulate cortices. In people with epilepsy, most functional neuroimaging studies have focused on facial emotion recognition, primarily in patients with temporal lobe epilepsy. Nevertheless, across various domains of social cognition, abnormal activations and disrupted connectivity within social cognition networks are consistently observed, regardless of the focus location. Aberrant connectivity has also been noted in the few studies involving patients with generalized epilepsy. In focal epilepsy, the amygdala remains a central region for facial emotion recognition, irrespective of whether the epilepsy is localized to the temporal or frontal lobes. For theory of mind studies, regions typically identified in healthy individuals, such as the medial prefrontal cortex, exhibit either hyperactivation or reduced activation in people with focal epilepsy, complicating interpretation. In the domain of empathy, a study involving patients with idiopathic generalized epilepsy reported decreased activation in core regions commonly identified in healthy individuals, particularly the anterior cingulate cortex and anterior insula. The limited data available in the literature suggest that key regions shared between social cognition and epilepsy networks consistently contribute to these disruptions and may serve as potential targets for future neuromodulation interventions.

To evaluate the availability and consistency of commercial driving eligibility criteria for patients with seizures.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy marked by drug-resistant seizures and profound cognitive and behavioral impairments, with nearly 95% of individuals affected by moderate to severe intellectual disability. This review comprehensively explores the cognitive and behavioral impacts of current treatment options for LGS, including antiseizure medications (ASMs), neuromodulation strategies, the ketogenic diet, and surgical interventions. Given the limited availability of LGS-specific data for several ASMs, the evidence base is supplemented with findings from general epilepsy populations and individuals with epilepsy and intellectual disabilities. The evidence reveals that ASMs exert varied cognitive and behavioral effects in LGS. Medications such as valproate, lamotrigine, cannabidiol, fenfluramine, levetiracetam, brivaracetam, felbamate, and rufinamide generally support cognitive stability, while topiramate and zonisamide are associated with cognitive challenges. Behavioral outcomes also vary: stability is observed with valproate, lamotrigine, rufinamide, cannabidiol, and fenfluramine, whereas medications like levetiracetam, perampanel, brivaracetam, clobazam, and zonisamide can increase aggression or irritability. Nonpharmacological therapies, particularly when they reduce seizure frequency, typically provide greater cognitive and behavioral stability, with some offering improvement. Early intervention-especially through surgical options-appears most beneficial for preserving cognitive function. Additionally, therapies such as the ketogenic diet and neuromodulation may provide independent cognitive benefits beyond seizure control. This review emphasizes the importance of personalized treatment strategies, integrating cognitive and behavioral evaluations in therapy selection. Key components include baseline cognitive and behavioral assessments, followed by regular follow-up evaluations, particularly after therapy changes. Consideration of minimizing ASM polytherapy, careful evaluation of drug-drug interactions, pharmacogenomic implications, and the need for therapeutic drug monitoring in cases of cognitive adverse effects is essential. Future research should focus on developing assessment tools tailored to the unique needs of individuals with LGS, utilizing connectivity measures to assess intervention impacts, and advancing precision therapeutics to improve cognitive and behavioral outcomes.

The objective of this study was to evaluate the effect of seletracetam (SEL), a potent modulator of synaptic vesicle glycoprotein 2A (SV2A), in patients with photoparoxysmal EEG response (PPR) to intermittent photic stimulation (IPS) as proof-of-principle of efficacy in patients with epilepsy. In this multicenter, single-blind Phase II study, adults with photosensitive epilepsy, with/without concomitant antiseizure medication therapy, underwent IPS under 3 eye conditions (at eye closure, eyes closed and eyes open) after a single oral dose of placebo (day - 1) or SEL (day 1; 0.5, 1, 2, 4, 10, or 20 mg). Complete suppression was a standardized photosensitivity range reduction to 0 over ≥ 1 time points for all eye conditions. Partial suppression was a ≥ 3-point reduction over ≥ 3 testing times vs the same time points on day - 1 in ≥ 1 eye condition. In addition, pharmacokinetics and safety were assessed. Of 27 evaluable patients, 9 reentered to receive a 2nd dosing 1-6 months later, providing a total of 36 individual exposures. At all doses administered - even the lowest -, several subjects reached a complete abolishment of PPR, with a rapid onset of effect. Overall, complete abolishment of PPR was obtained in 40-71 % of the patients; the effect increasing with the dose. In terms of effective doses to suppress PPR, SEL was at least 1,500 times more potent than levetiracetam and 10-20 times more potent than brivaracetam. Adverse events of SEL, including dizziness and somnolence, were mild to moderate. Pharmacokinetics of SEL demonstrated rapid absorption and a linear dose:plasma level relationship. This proof-of-principle study demonstrates that - based on our own experience - SEL is the most potent compound ever tested in the photosensitivity model.

The rising incidence of epilepsy has not been accompanied by sufficient public education, contributing to persistent social stigma towards people with epilepsy. This stigma leads to their exclusion and discrimination in key areas such as employment, education, and social interactions, ultimately diminishing their quality of life. This study aimed to assess the attitudes of medical students, resident doctors, and nurses toward people with epilepsy in three large cities in Indonesia.

This study aimed to evaluate the impact of a computer-assisted rehabilitation program on self-management, cognitive function, and quality of life in people with epilepsy (PwE).

In people with intellectual disability (ID), prevalence of epilepsy can be over 40-times higher than in normally intelligent people, impacting quality of life (QoL) of those affected. Patients with ID are often excluded from clinical trials, resulting in limited evidence regarding treatment. This study aimed to evaluate effects of a comprehensive inpatient treatment program on seizure outcome and QoL and to identify predictive factors for improvement in these measures.

RINCH (Rhythmic Ictal Non-Clonic Hand movements), a lateralizing sign in frontotemporal epilepsy, has been well described in the adult epilepsy population but not in the pediatric setting. We looked for evidence of RINCH as an ictal sign in pediatric epilepsy monitoring unit reports in a large academic pediatric hospital. We found nine patients with RINCH ictal phenomenon over a five-year period. We compared the characteristics of their epilepsy to the known data in adult patients. The patient age range was 6-15 years. Five patients had a lesion in the temporal lobe; the remaining four were non-lesional. The ictal EEG onset was in one temporal lobe in five patients. The remaining patients had frontal or non-localizable onset. However, ictal activity was present in the frontal lobe(s) in six patients at the time of RINCH. Seven occurrences of RINCH were contralateral to the epileptogenic lesion and/or ictal scalp EEG activity. The remaining patients were non-lesional with bilateral frontotemporal ictal activity. Dystonia was ipsilateral to the RINCH in two patients. This study reinforces the lateralizing significance of RINCH as an ictal phenomenon when it is present. RINCH may be rare in the pediatric epilepsy population, but it may also be under-reported.

This study was conducted to investigate the relationship between caregiver burden and life satisfaction among caregivers of individuals with epilepsy.

Epilepsy is a condition associated with stigma and considerable morbidity, placing a significant burden on patients and their families. It is fundamental to be mindful of the fact that a substantial number of patients remain unaware of the effective surgical procedures that have shown great success in many cases, drawing upon the global underutilization of epilepsy surgery (ES). In this study, we explore the knowledge and attitudes of epilepsy patients towards ES at Jordan University Hospital (JUH).

Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, specific electroencephalogram (EEG) patterns, and significant cognitive and behavioral impairments. To date, eight anti-seizure medications (ASMs) have been specifically approved by the U.S. Food and Drug Administration (FDA) for the treatment of LGS: clonazepam, felbamate, lamotrigine, topiramate, rufinamide, clobazam, cannabidiol, and fenfluramine. Additionally, several other ASMs, including valproate, are frequently used off-label for LGS management. As the therapeutic landscape for LGS expands, clinicians are increasingly faced with complex decisions regarding optimal ASM selection. This narrative review explores evolving treatment strategies, offering a consensus-based treatment algorithm designed by a panel of U.S.- based experts. We analyze both FDA-approved and off-label ASMs, drawing on data from randomized controlled trials, open-label extensions, and real-world studies to assess each drug's efficacy and safety profile. A key challenge in comparing ASMs lies in the heterogeneity of study designs and outcome measures. This review addresses these limitations and considers crucial factors influencing ASM selection, such as seizure outcomes, safety profiles, cognitive and behavioral outcomes, drug-drug interactions, and rational polypharmacy. Barriers to access, including economic and regulatory hurdles, are also discussed. The proposed treatment algorithm emphasizes a personalized approach to LGS management, recommending valproate or clobazam as first-line treatments, followed by individualized combinations based on the specific patient profile and associated comorbidities.

Epilepsy imposes substantial challenges on informal caregivers, who play a vital role in supporting individuals with this condition. This review aims to explore the burden experienced by informal caregivers of adults with epilepsy and identify critical factors that influence their overall experience. A literature review was conducted following PRISMA guidelines. PubMed and ScienceDirect were searched for identifying original research articles published in English from January 2005 till the end of February 2024. Studies were critically appraised using the AXIS Critical Appraisal Tool for Cross-Sectional Studies. Data were extracted and a narrative synthesis was performed. Twelve studies involving 1.265 participants were included. Eight studies were rated as high quality, while four were rated as fair quality. Six primary determinants of caregiver burden were identified: care-recipient characteristics, caregiver characteristics, psychological and physical factors, availability of support system, ethnicity and culture, and stigma. The majority of studies reported mild-to-moderate levels of caregiver burden, reflecting the diverse challenges faced by caregivers providing assistance to adults with epilepsy. While this review identifies several factors influencing caregiver burden, prospective longitudinal and qualitative studies are essential to unravel the multidimensional nature of caregiver burden and its variations across diverse cultural settings.

Caregiving for adults with epilepsy (AWE) imposes a different degree and scope of challenges than for children and teenagers with epilepsy, and it remains understudied. This study aimed to identify the types of caregiver burdens, needs, and coping strategies in caregiving for AWE.

Traumatic brain injury is a significant risk factor for the development of post-traumatic epilepsy (PTE), posing a major clinical challenge. This review discusses the critical role of GABAergic interneurons and reactive astrogliosis in the pathophysiology of post-traumatic epilepsy, integrating findings from our research group within the traumatic brain injury context with recent literature to highlight the impact of excitation-inhibition imbalance. We analyzed alterations in interneuron populations, specifically subtypes expressing the calcium-binding proteins parvalbumin, calretinin, and calbindin, and their association with an increased risk of epileptogenesis after TBI. Furthermore, we detail the role of reactive astrogliosis, elucidating how dysregulated astrocytic functions, including impaired glutamate homeostasis and aberrant calcium signaling, contribute to an environment conducive to seizure activity. Increased expression of glial fibrillary acidic protein and crystallin alpha-B in reactive astrocytes identified in contused human tissue suggests their involvement in exacerbating epileptogenic circuits. Our findings emphasize the intricate interactions between GABAergic interneurons and astrocytes, underscoring the need for a comprehensive understanding of the mechanisms underlying post-traumatic epilepsy. By bridging our group's data with existing evidence, this review establishes a foundation for future studies aimed at validating systemic biomarkers and developing targeted therapies to prevent or mitigate epilepsy progression following TBI. These insights are essential for addressing the complexities of drug-resistant epilepsy in affected patients.

Recent studies have shown that late-onset epilepsy (LOE) is accompanied with cognitive decline and increased risk of dementia, particularly Alzheimer's disease (AD). However, the pathophysiological mechanism underlying the cognitive decline in LOE remains unclear. The aim of current study was to evaluate the relationship between glymphatic system (GS) function and cognitive decline in LOE patients using the diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS).

The rising cost of anti-seizure medications (ASMs) in the United States (US) is a major concern for patients, healthcare providers, insurance payors, and policymakers. We aim to describe and analyze the spending trends on ASMs in the Medicare Part D (MPD) and Medicaid population in the US.

This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures in April 2024. Status Epilepticus (SE) is a neurological emergency involving prolonged seizures that disrupt brain function and may cause severe, long-term neurological damage. Developmental and Epileptic Encephalopathies (DEEs), a group of severe genetic disorders with early-onset epilepsy, often exhibit SE episodes that compound their inherent cognitive and developmental challenges. In patients with DEEs, SE may intensify excitotoxicity, metabolic strain, and neuroinflammatory processes, exacerbating developmental delays and cognitive deficits. SE episodes in DEEs frequently resist conventional anti-seizure medications, posing heightened risks of progressive neurological decline and mortality. This paper explores how SE contributes to worsening neurodevelopmental outcomes in DEEs, particularly through sustained structural and functional brain alterations observed in human neuroimaging and animal models. Findings from clinical studies and neuroimaging highlight SE's role in structural damage, including cortical atrophy, hippocampal sclerosis, and gray matter loss. Rodent models replicate SE through chemical or electrical induction, providing insights into SE-induced neurodegeneration, network reorganization, especially in critical areas like the hippocampus, which is more known, however few of scientists look that much outside it. The models reveal a progressive cycle where recurrent SE episodes increase brain excitability, predisposing to further seizures and cumulative developmental impairment. Moreover, genetic animal models of DEEs suggest that early-life seizures exacerbate the severity of the epilepsy phenotype and neurocognitive deficits. This paper underscores the need for advanced, individualized therapies to manage SE in DEE patients and prevent recurrence, aiming to minimize long-term neurological and developmental sequelae.