Epilepsy Population Research Articles

Adverse events associated with carbamazepine: a pharmacovigilance study using the FDA Adverse Event Reporting System

ABSTRACT Introduction Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation. Areas covered Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ. Expert opinion In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.

Contribution of prefrontal cortex and ventral hippocampus to anxiety in young epileptic mice

Children with epilepsy are particularly vulnerable to anxiety disorders, where these disorders are frequently underdiagnosed and untreated. Despite the high prevalence of anxiety in epilepsy, the underlying neurobiological mechanisms are not fully understood. The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) are key brain regions implicated in the genesis and modulation of anxiety, and their interactions play a crucial role in emotional processing including anxiety. We utilized a pilocarpine-induced epilepsy model in young mice (7 weeks old) to assess anxiety-like behaviors using the open field test (OFT), light/dark box, and elevated plus maze (EPM). Local field potential (LFP) recordings were conducted to examine theta power and coherence between the mPFC and vHPC. LFP recordings revealed significantly altered theta power variation in both the mPFC and vHPC during exposure to anxiogenic contexts, suggesting the involvement of these regions in anxiety in the young epileptic mice. Notably, theta-frequency synchrony between the mPFC and vHPC was not significantly altered in the young epileptic mice, indicating that altered theta power rather than inter-regional synchrony may underlie anxiety behaviors in young epileptic mice. Furthermore, we demonstrated that chemogenetic inhibition of excitatory neurons in the mPFC and vHPC reduced anxiety levels in young epileptic mice. Altogether, our findings highlight the critical contributions of mPFC and vHPC to the pathogenesis of comorbid anxiety in epilepsy. These findings underscore the potential therapeutic significance of modulating the activity in these two regions as means to alleviate anxiety in a youth epilepsy population.

Association of hyperventilation-induced heart rate variability and sudden unexpected death in epilepsy in drug-resistant epilepsy.

Within the general epilepsy population, the incidence of Sudden Unexpected Death in Epilepsy (SUDEP) ranges from approximately 0.35 to 2.3 per 1,000 individuals per year. We aimed to evaluate the relationship between SUDEP risk factors and heart rate variability (HRV) parameters as a potential biomarker of SUDEP in patients with drug-resistant epilepsy (DRE). There were 52 patients diagnosed with DRE and under follow-up, and controls including 45 healthy subjects, included in the study. Hyperventilation-induced HRV (HRVHV) parameters, including the standard deviation of all RR intervals (SDRR), mean heart rate (HR), root mean squares of successive differences (RMSSD), SD of mean NN intervals recordings (SDANN), and HRV triangular index, were assessed during resting. To predict the risk of SUDEP, the relationship between HRV parameters and SUDEP risks was evaluated using the Risk Assessment for Sudden Death in Epilepsy (SUDEP-7) Risk Inventory. No statistically significant difference was found in sympathetic skin response (SSR) latency and amplitudes between the patient and control groups. In comparing healthy control subjects with patients experiencing DRE, we observed significant decreases in SDRRHV and hyperventilation-induced RMSSD (RMSSDHV) values, specifically within HRVHV. Notably, a significant correlation emerged concerning the RMSSDHV values (p < 0.01), when examining the correlation between the SUDEP-7 inventory and HRVHV parameters. This correlation between RMSSDHV and the SUDEP-7 Risk Inventory in patients with DRE represents a novel and consequential finding, suggesting its potential as an indicator of SUDEP risk.

Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures in adults.

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient-reported or caregiver-reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep-related outcomes. Of the 2830 citations identified, 136 were included. Most studies were in the focal epilepsy population; very few studies reported outcomes in the PGTCS population. The presence of epilepsy-specific instruments varied based on the domain evaluated. Epilepsy exerted considerable humanistic and economic burden. Indicators of poor disease control (e.g., high seizure frequency, resistance to anti-seizure medications, polypharmacy) increased epilepsy burden. Seizure frequency and type, disease severity, and polypharmacy also affected work productivity. Adults with epilepsy, particularly focal epilepsy, reported higher indirect costs, more sick days accrued, and early entry into retirement. Caregivers similarly reported high productivity loss and absenteeism related to caregiving duties. The results of this SLR highlight the high humanistic and economic burden of focal epilepsy and PGTCS, although limited data were available for the PGTCS population. The results include patient-reported outcome data specific to focal epilepsy and PGTCS, expanding the limited humanistic burden evidence identified in previous reviews, and show the effect of poor disease control on individuals' lives and as a driver of indirect costs. PLAIN LANGUAGE SUMMARY: Our systematic literature review identified studies that evaluated the impact of focal epilepsy and primary generalized tonic-clonic seizures on patients and their caregivers. We found that focal epilepsy negatively impacted patients' mental health and sleep and was associated with higher indirect costs and lower work productivity in people with more severe disease. The impact of primary generalized tonic-clonic seizures on patients was rarely reported, and future research is needed.

The incidence of sudden unexpected death in epilepsy (SUDEP) in the Republic of Ireland

BackgroundThe incidence of sudden unexpected death in epilepsy (SUDEP) in Ireland has previously been studied in only a small geographical area. Our aim was to calculate an incidence rate for the whole of the Republic of Ireland in 2019. MethodsAll deaths referred to the coroner in 2019 were examined. Those with a history of possible epilepsy were noted and subjected to a more detailed assessment. Cases fulfilling the definition of definite SUDEP were identified. The incidence of SUDEP was calculated using the population of the Republic of Ireland in 2019 and the known prevalence of epilepsy in Ireland. ResultsThirty-three cases of definite SUDEP were identified in the Republic of Ireland in 2019. The estimated incidence of SUDEP in the epilepsy population as a whole was 0.7/1000(0.46 – 0.94) person years. This may be a conservative estimate. More men than women were identified, and most individuals were found dead at home. SUDEP was mentioned on the death certificate in only 52 % of cases. ConclusionThis is the first nationwide study of SUDEP incidence in Ireland and provides an incidence rate in keeping with other populations. This work demonstrates that the interrogation of coronial records is a useful way to monitor epilepsy mortality albeit with certain limitations.

Performance validity in a presurgical epilepsy population

Objective: This study examined the performance validity test (PVT) pass/fail rate in a sample of presurgical epilepsy candidates; assessed whether performance validity was associated with reduced performance across cognitive domains; investigated the relationship between performance validity and self-report mood questionnaires; and assessed whether PVT performance was associated with demographic or clinical factors (i.e. sex, race/ethnicity, age, years of education, reported history of special education, seizure longevity, and number of anti-seizure medications). Methods: One hundred and eighty-three presurgical epilepsy candidates were examined. Each patient’s assessment battery included a stand-alone performance validity measure and two embedded validity measures. Results: PVT failure rate in this sample (10%) was associated with reduced performance on all neurocognitive measures: Full Scale IQ (FSIQ; r = −0.26), CVLT-II Total Learning (r = −0.36) and Long Delay Free Recall (LDFR; r = −0.38), BVMT-R Delayed Recall (r = −0.28), and Wisconsin Card Sorting Test (Categories Completed; r = −0.32). In addition, PVT failure rate was associated with elevated scores on the Beck Anxiety Inventory (r = .22) but not on the Beck Depression Inventory (BDI-II; r = .14). Correlations that were significant at the α = 0.05 level maintained significance following post hoc Bonferroni correction. The valid and invalid groups did not differ significantly in sex, race/ethnicity, age, years of education, reported history of special education, seizure longevity, and number of anti-seizure medications. Conclusions: Results from this study suggest that PVT performance was not impacted by demographic or clinical factors and therefore may be a reliable indicator of performance validity in a presurgical epilepsy sample.

Neurocognition in Pediatric Temporal Lobe Tumor-Related Epilepsy.

Tumor-related epilepsy is a common and understudied neurological comorbidity among pediatric temporal lobe tumor patients that poses risk for neurocognitive impairment (NCI). Forty-one youth with either TLT+ (n = 23) or nonneoplastic temporal lobe epilepsy (n = 18) ages 6-20 years completed routine neuropsychological evaluations. Rates of NCI were similar across groups; however, NCI was more common in nonneoplastic participants on a task of phonemic fluency, p = .047. Younger age of seizure onset and greater number of antiseizure medications were associated with NCI among TLT+ participants only. Preliminary findings suggest separate prognostic models of cognitive outcomes between TLT+ and nonneoplastic epilepsy populations may be needed.

Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: A cross-sectional study.

Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation. The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.

Surveying neurologist perspectives and knowledge of epilepsy surgery to identify barriers to surgery referral.

Epilepsy surgery is an effective means of treating medically refractory epilepsy (MRE), but it remains underused. We aimed to analyze the perspectives and knowledge of referring neurologists in the New York metropolitan area, who serve a large epilepsy population. We adapted a previous Canadian survey by Roberts etal. (2015), adding questions regarding demographic descriptors, insurance coverage, training and practice details, and perceived social barriers for patients. We surveyed neurologists directly affiliated with Montefiore Medical Center and those referring to Montefiore's Comprehensive Epilepsy Center. Participants had 10 weeks to fill out an online Qualtrics survey with weekly reminders. Of 117 neurologists contacted, 51 eligible neurologists completed the survey (63.8% Montefiore, 35.0% referring group). A high proportion of the results were from epilepsy-trained individuals (41.2%) and neurologists who graduated residency ≤19 years ago (80.4%). 80.4% of respondents felt that epilepsy surgery is safe, but only 56.9% would refer a patient for surgical workup after two failed trials of anti-seizure medications. Epileptologists and providers with a larger volume of epilepsy patients and electroencephalogram readings had better knowledge of the epilepsy surgery workup guidelines. When asked to rank social barriers to patients receiving surgery, participants were most concerned about lack of social support, financial insecurity, and a patient's dual role as a caregiver. Our study suggests continued reluctance of neurologists regarding epilepsy surgery, and deficiencies in the knowledge and adherence to the recommended guidelines. In the context of prior studies, these results showed improved understanding of the definition of MRE (80.4%) and an increased likelihood to refer eligible patients as early as possible (78.4%) in line with current consensus recommendations. The finding that epilepsy-trained and more epilepsy/electroencephalogram-facing neurologists showed better understanding of the guidelines suggests that increased education efforts should be targeted at non-epileptologists. Our study asked New York City doctors about their approach to epilepsy surgery. Many do not consider it as early as they could in treatment plans. The doctors with extra epilepsy training were better at knowing when to consider surgery.

Seizures in Multiple Sclerosis are, above all, a Matter of Brain Viability

Objectives: Most patients with Multiple Sclerosis (MS) never have a seizure, although they are at risk for seizures since the onset of MS. This paradox leads us to suppose that MS plays a minor role in seizure generation and epileptogenesis. Methods: Qualitative study using data triangulation and inductive content analysis. A comprehensive literature search was carried out in four electronic databases (MEDLINE, Embase, Web of Science, and Google Scholar). Results: In MS patients, unprovoked seizures occur rarely (in about 3 percent of cases). Pediatric MS involves seizures more common than adult or late-onset MS. In general, children with seizures do not have poorer MS prognoses than children without seizures. Contrary to the general population, seizures do not peak in older MS patients. Since the use of disease-modifying therapies in the treatment of MS (i.e., since 1993), the frequency of seizures in MS patients has not changed considerably. Epilepsy syndrome cannot be recognized in MS patients with seizures. As a rule, seizures in MS are not difficult to treat. A sudden unexpected death in MS patients with seizures has not been observed more commonly than in the general epilepsy population. A disruption of the blood–brain barrier is the most obvious proconvulsive factor of MS. However, neither MS relapses nor a high rate of MS relapses is normally accompanied by seizures. Structural brain abnormalities usually accumulate over the course of MS. However, a high brain magnetic resonance imaging lesion load does not have a substantial impact on seizure occurrence in MS. Conclusion: MS does not have a major role in seizure generation and epileptogenesis. In most cases, the seizure-promoting effects of MS can be successfully counteracted by the brain´s protective mechanisms.

Stereoelectroencephalography-Guided Radiofrequency Thermocoagulation: Diagnostic and Therapeutic Implications.

Despite recent medical therapeutic advances, approximately one third of patients do not attain seizure freedom with medications. This drug-resistant epilepsy population suffers from heightened morbidity and mortality. In appropriate patients, resective epilepsy surgery is far superior to continued medical therapy. Despite this efficacy, there remain drawbacks to traditional epilepsy surgery, such as the morbidity of open neurosurgical procedures as well as neuropsychological adverse effects. SEEG-guided Radiofrequency Thermocoagulation (SgRFTC) is a minimally invasive, electrophysiology-guided intervention with both diagnostic and therapeutic implications for drug-resistant epilepsy that offers a convenient adjunct or alternative to ablative and resective approaches. We review the international experience with this procedure, including methodologies, diagnostic benefit, therapeutic benefit, and safety considerations. We propose a framework in which SgRFTC may be incorporated into intracranial EEG evaluations alongside passive recording. Lastly, we discuss the potential role of SgRFTC in both delineating and reorganizing epilepsy networks.

36 Impact of Neuropsychological Performance and Anxiety on Meditation in Drug Resistant Epilepsy (DRE) Patients Implanted with a Responsive Neurostimulation (RNS) Device

Objective:Responsive neurostimulation (RNS) is a surgical intervention to reduce the frequency of seizures as an adjunctive therapy for patients with drug-resistant epilepsy (DRE). Presurgical neuropsychological evaluations capture symptoms of anxiety and depression, which occur in higher rates within the epilepsy population than in the general population; however, the effects of mood are commonly overlooked or underappreciated in the conceptualization of cognitive functioning and overall quality of life. Previous studies have shown the effects of attentional control and executive functioning on engagement in meditative states. The present study examines pre and post-meditation self-reported anxiety symptoms and the electrophysiological changes captured intracranially during meditation sessions in patients implanted with an RNS device. This study seeks to utilize presurgical neuropsychological evaluations to explore relationships between cognitive profiles and meditative state changes, and reductions in anxiety.Participants and Methods:This study presents a series of 10 patients who underwent RNS device implantation for the treatment of DRE at Mount Sinai Hospital. All patients had at least one contact in the basolateral amygdala. Prior to surgical implantation of the RNS device, all patients completed a comprehensive neuropsychological evaluation based on the NIH Common Data Elements Battery for Epilepsy Patients. Patients in this study completed a 17-and 22-minute meditation protocol based on loving-kindness and Focal Awareness (FA) meditation. Control points and mind-wandering phases were utilized to distinguish the meditative portion of the study during intracranial recordings. All patients completed a pre- and post-meditation questionnaire adapted from the PROMIS Anxiety Short Form as well as self-ratings on meditation depth and satisfaction.Results:Presurgical neuropsychological evaluation of patients showed elevated levels of anxiety on the BAI (M = 18.14, SD = 12.03) and depression on the BDI-II (M = 15.57, SD = 6.92). Neuropsychological findings localized to frontal or frontotemporal deficits in 80% of the patients were captured in this study. Regarding lateralization, 50% of patients presented with bilateral weakness on neuropsychological evaluation, with the rest showing unilateral profiles. A negative correlation was observed between patient responses on pre-meditation anxiety measures and self-reported depth of engagement in meditation, r = -0.65, p = .043. When all meditation sessions were evaluated, patients displayed a reduction in anxiety levels pre- and post- meditation, t = 2.3, p = .03.Conclusions:Present findings suggest a reduction in anxiety symptoms following completion of a meditation paradigm. Additionally, a relationship between anxiety and depth of engagement in meditation was identified. During each meditation session, electrocorticography data was collected and analyzed. Given the high comorbidities of anxiety and depression as well as cognitive symptoms common for individuals with epilepsy, a systems-based approach may enhance conceptualization of neuropsychological and neuropsychiatric evaluations, which may have a significant clinical impact. Evaluation of neuropsychological profiles, meditation effects, and anxiety in this population may support cross-discipline understanding of cognitive and psychiatric profiles to better inform treatment recommendations.

37 Cognitive Disengagement Syndrome (CDS; Sluggish Cognitive Tempo) in Pediatric Epilepsy

Objective:Cognitive disengagement syndrome (CDS; previously known as “sluggish cognitive tempo” or SCT) refers to a set of behavioral symptoms characterized by slowed thinking/behavior, daydreaming, and mental fogginess or confusion. It has been described as related to, yet separate from, symptoms associated with Attention-deficit Hyperactivity Disorder (ADHD) inattention. There is a paucity of research on CDS within pediatric epilepsy populations despite substantial risk factors inherent to the disorder and a large proportion of patients with comorbid ADHD. This study therefore describes CDS as reported by parents for a large sample of children with epilepsy. Relationship between epilepsy variables (e.g., number of antiepileptic drugs [AEDs], seizure frequency, seizure type) and CDS symptoms was explored. Additionally, considering the negative association between CDS and academic performance in other populations, the relationship between parentrated CDS and academic risk factors was examined.Participants and Methods:Participants included 151 children with epilepsy (mean age = 11y, range 6-18y; 55% male; IQ&gt;70), referred for outpatient neuropsychological assessment. As part of routine clinical care, parents completed the Penny Sluggish Cognitive Tempo Scale (SCT) and the Colorado Learning Difficulties Questionnaire (CLDQ). Scores and basic demographic information were extracted from an IRB approved clinical database; the IRB granted approval for retrospective chart review to extract additional medical variables. Parent report of CDS included total CDS score and three subdomains: Sleepy/Sluggish, Low Initiation, and Daydreamy. Higher scores represent greater parent-reported difficulties. Independent samples t-tests compared the participants’ means on total CDS and each subdomain to the normative sample. Analysis of variance was conducted to determine differential impact of seizure type (Generalized, Focal, or Multifocal) on total CDS and each subdomain. Correlations between other medical variables, scores on the CLDQ, and parent ratings on the SCT were examined.Results:Parents of children with epilepsy rated overall CDS total and subdomain scores as significantly higher compared to the normative means with highest elevation in symptoms of Low Initiation (p = &lt;.001). Total CDS was associated with increased parent-reported academic difficulties; however, of the three subdomains, only Low Initiation was significantly associated with concerns for academic functioning. Number of AEDs was associated with increased symptoms on the Sleepy/Sluggish subdomain only. Seizure frequency was associated with total CDS and Sleepy/Sluggish symptoms, though this finding is likely mediated by increased number of AEDs for those with more frequent seizures. Seizure type was not associated with significant differences in Total CDS or CDS subdomains.Conclusions:Children with epilepsy are at increased risk for experiencing slowed thinking and cognitive disengagement. Low initiation is particularly elevated in pediatric epilepsy populations, which may lead to increased academic difficulties. Potential interventions targeting low initiation may therefore have benefit in the academic setting for children with epilepsy, regardless of epilepsy type.

5 The impact of recreational cannabis use on neuropsychological function in epilepsy

Objective:Cannabis is classified as a class B drug in the UK with penalties for possession of up to 5 years in prison, an unlimited fine or both. Nevertheless it is widely available and is the most commonly used drug in the UK with approximately 2.6 million (7.6%) of adults reporting that they sometimes or regularly use it. It is not uncommon for people who present in our epilepsy clinic to report regular use of cannabis; some use it recreationally whilst others report ‘self-medicating’ based on the belief that it has a beneficial impact on their seizures. The aim of this study was to establish the prevalence of cannabis use in people with epilepsy referred for a neuropsychological assessment and to examine the impact of cannabis use on cognitive function in this group.Participants and Methods:All patients who attend for a neuropsychological assessment are routinely asked about illegal drug use in their clinical interview. This information is also captured in the medical and neuropsychiatric assessments they undergo when assessed by the multidisciplinary team. The electronic medical records of 800 consecutive patients who had undergone a neuropsychological assessment between 2019 and 2022 were searched for references to cannabis use. The neuropsychological profiles of patients reporting cannabis use were compared to those seen in the larger series across multiple cognitive domains.Results:Seventy (8.75%) of the patients in the series reported past or present cannabis use. Cannabis users were more likely to be male (p&lt;0.01) and were younger (p&lt;0.01) than those who did not report use. Reading IQ was significantly lower in the cannabis group (p&lt;0.001). Patients who were regularly using cannabis at the time of the neuropsychological assessment did not differ from the rest of the cohort on tests of processing speed, working memory, naming or verbal fluency. There were no differences between the groups in their performance on an embedded measure of performance validity. However the patients who were regularly using cannabis at the time of their neuropsychological assessments scored significantly lower on tests of verbal learning (p&lt;0.05) and reported significantly greater subjective memory problems in everyday life (p=0.02) than the non-cannabis group. The group using cannabis also scored significantly more highly on the depression (p&lt;0.01) and anxiety scales (p=0.02) on the Hospital Anxiety and Depression Scale.Conclusions:The prevalence and patterns of cannabis use in the epilepsy population mirror those seen in the wider population. The impact on regular cannabis use on neuropsychological function appears to be most evident on measures of new learning and subjective measures of memory disturbance. Cannabis use is significantly associated with lower levels of cognitive reserve and elevated levels of anxiety and low mood. Whilst caution must be employed with respect to any direct attribution in these complex clinical presentations, these findings may be helpful in the interpretation of neuropsychological test scores and the planning of interventions, particularly with respect to subjective memory complaints in this group.

Integrated Macrogenomics and Metabolomics Explore Alterations and Correlation between Gut Microbiota and Serum Metabolites in Adult Epileptic Patients: A Pilot Study.

Epilepsy (EP) is a complex brain disorder showing a lot of unknows reasons. Recent studies showed that gut microbiota can influence epilepsy via the brain-gut axis. Nevertheless, the mechanism by which gut microbiota affects adult epilepsy still remains unclear. In this study, fecal and serum samples were obtained from patients with epilepsy and normal controls. Using an integrated analysis, sequencing was performed by macrogenomics and high-throughput targeted metabolomics with various bioinformatics approaches. The macrogenomic sequencing revealed significant changes in microbial structure in patients suffering from epilepsy. For example, at the phylum level, the relative abundance of Actinobacteria, Bacteroidetes and Proteobacteria showed an increase in the patients with epilepsy, whereas that of Firmicutes decreased. In addition, the patients with epilepsy had significantly differential metabolite profiles compared to normal controls, and five clusters with 21 metabolites, mainly containing the upregulation of some fatty acids and downregulation of some amino acids. Tryptophan (AUC = 91.81, p < 0.0001), kynurenine (AUC = 79.09, p < 0.01) and 7Z,10Z,13Z,16Z-Docosatetraenoic acid (AUC = 80.95, p < 0.01) may be used as potential diagnostic markers for epilepsy. Differential serum metabolites have effects on tryptophan metabolism, iron death and other pathways. Furthermore, a multiomic joint analysis observed a statistically significant correlation between the differential flora and the differential serum metabolites. In our findings, a macrogenomic analysis revealed the presence of dysregulated intestinal flora species and function in adult epileptic patients. Deeper metabolomic analyses revealed differences in serum metabolites between patients with epilepsy and healthy populations. Meanwhile, the multiomic combination showed connection between the gut microbes and circulating metabolites in the EP patients, which may be potential therapeutic targets.

Influence of sleep disturbance, depression, anxiety, and stress on quality of life in people with epilepsy.

We assessed the quality of life, sleep, depression, anxiety, and stress in people with pharmacoresistant epilepsy (PRE) and newly diagnosed epilepsy (NDE). We also assessed the influence of sleep, depression, anxiety, and stress on the quality of life (QOL) and the complex association between these factors. We recruited 80 PRE and 70 NDE people attending the epilepsy clinic. We assessed QOL, sleep quality, daytime sleepiness, and mood using the quality of life in epilepsy-31 inventory (QOLIE-31), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and depression anxiety stress scale (DASS-21). We compared the results between the two groups of epilepsy populations. We performed univariate and multivariate linear regression to determine the factors affecting the QOLIE-31 total score. We applied Spearman's rank correlation to find the interrelationship between variables influencing QOL. We found significantly lower QOLIE-31 total scores (p = .001) in PRE compared to NDE. The PSQI and ESS did not differ significantly between the PRE and NDE groups. Anxiety (p = .002) and stress (p = .003) scores were significantly higher in PRE than in NDE. QOLIE-31 total scores showed a negative correlation with PSQI as well as symptoms of depression, anxiety, and stress scores in both groups. Multiple linear regression analysis revealed depression as a major factor influencing the QOLIE-31 total score in PRE (p = .001) and NDE (p = .003). We found significant complex associations between PSQI, depression, anxiety, stress, and QOLIE total scores in both groups. The QOL is poorer for people with PRE than for those with NDE. Depression is a major determinant of QOL in PWE. These factors need to be considered to improve the QOL in epilepsy.

Comparison of psychosocial screeners in an epilepsy clinic

Screenings are recommended for co-occurring conditions in pediatric epilepsy. However, there is limited research regarding which screener to implement in the clinic. This study aimed to compare different screening measures for attention-deficit/hyperactivity disorder (ADHD) and emotional concerns in a pediatric epilepsy population during a routine neurology clinic visit. Fifty (22%) of 226 contacted parents of children with epilepsy ages 5–17 years old agreed to participate. Screening measures included the Strengths and Difficulties Questionnaire (SDQ; Hyperactivity/Inattention (ADHD), Emotional Problems (E) subscales), the Pediatric Quality of Life Inventory Epilepsy Module (PedsQL-EM; Executive Functioning (EF), Mood/Behavior (M/B) subscales), and the ADHD Rating Scale (ADHD-RS). Analyses comparing measures included Chi Square, Pearson’s correlation, and agreement statistics (Cohen’s kappa, overall agreement). Consistent with prior literature, positive screening rates ranged from 40% to 72% for ADHD concerns and 38% to 46% for emotional concerns. Agreement between measures ranged from fair to substantial, with the highest agreement (85%; κ = 0.70) between the SDQ-E and PedsQL-EM-M/B. Although all measures rendered positive screens within expected rates, there are differences among the measures that inform screening measure selection.

Evaluation of a pilot Tree of Life group for children with epilepsy and their families.

Tree of Life Groups (a narrative therapy technique) have been used successfully in a number of paediatric populations. The group intervention aims to give children a space to express their difficulties whilst also holding in mind their strengths and hopes, thereby creating a preferred identity incorporating their physical health condition. No studies were identified which described this approach in a paediatric epilepsy population or involving siblings, families and the multidisciplinary team. The current paper describes a pilot intervention to facilitate a one-day psychoeducational Tree of Life group for children with epilepsy, their siblings and parents. Separate parent and sibling groups were facilitated concurrently. The groups were co-facilitated by Paediatric Psychology and Paediatric Epilepsy team members. Quantitative feedback was completed by the patient group. Patients, siblings, and parents provided qualitative feedback. A total of 6 patients, 14 siblings and 15 parents attended the group. Quantitative feedback indicated some improvement in patients' confidence and knowledge of managing epilepsy, as well as some improvements in psychological adjustment and thoughts about epilepsy. 87.5% of patients and siblings detailed that they would recommend the group to others. Qualitative feedback from patients, siblings and parents indicated the helpfulness of relating to others and safely expressing difficulties. The results indicated that this pilot group intervention was well received by children with epilepsy and their families. Future studies incorporating a larger sample are warranted to explore this further.

Identification of common core ion channel genes in epilepsy and Alzheimer's disease.

Although available literature indicates that the incidence of dementia in the epilepsy population and the risk of seizures in the Alzheimer's disease (AD) population are high, the specific genetic risk factors and the interaction mechanism are unclear, rendering rational genetic interpretation rather challenging. Our work aims to identify the common core ion channel genes in epilepsy and AD. In this study, we first integrated gene expression omnibus datasets (GSE48350 and GSE6834) on AD and epilepsy to identify differentially expressed genes (DEGs), performing Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs. The related protein-protein interaction (PPI) network was constructed for DEGs, and the hub gene was evaluated. A total of 2800 and 35 genes were identified in GSE48350 and GSE6834, and 12 DEGs were significantly differentially expressed between the datasets. KEGG pathway analysis showed that DEGs were primarily enriched in glutamatergic synapse and dopaminergic synapse pathways. SCN2A, GRIA1, and KCNJ9 were the hub genes with high connectivity. The findings suggest that the three genes, SCN2A, GRIA1, and KCNJ9, may serve as potential targets for treating AD comorbid with epilepsy.

Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population-based cohort study.

Historically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real-world data. Third-generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden. A multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy. A total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52-77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow-up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty-nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p = .010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16-3.51). Levetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow-up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.