Risk Of Epilepsy Research Articles

Risk of epilepsy after a first epileptic seizure with unknown etiology in elderly patients

Patients whose epilepsy begins with seizures with unknown etiology in old age have been studied to a limited extent. The aim is to clinically characterise these patients, and predict their risk of developing epilepsy in the long term. This is a retrospective observational study of patients over 55 years old experiencing a first epileptic seizure with unknown etiology. The data were collected from their clinical history, including electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) results. Eighty-seven patients (58.6% male; 71.5 ± 8.1 years) were included. The mean follow-up was 7.3 ± 4.9 years. The most common vascular risk factor was arterial hypertension (77%; n = 67). Focal seizures with altered consciousness were the most frequent type of seizure (44.8%; n = 39), followed by focal seizures evolving to bilateral tonic-clonic seizures (39.1%; n = 34). Brain MRI showed cortical atrophy (50%; n = 42) and signs of small-vessel vascular disease (SVVD) (67.8%; n = 57). Interictal epileptiform EEG abnormalities were observed in 43.7% (n = 38) of the patients, mostly with temporal localisations (94.7%; n = 36). 44.8% (n = 39) had mild cognitive impairment at baseline. Recurrence of seizures, which was observed in 49 patients (56.1%), occurred after a median of 12 months (interquartile range: 4.4-25.9). Finally, 71 patients (81.6%) developed epilepsy. The risk of epilepsy in the long term following a single seizure of unknown etiology in elderly patients is greater than 80%. Arterial hypertension and mild cognitive impairment at baseline are the most common clinical features. Cortical atrophy and the presence of SVVD are frequent in MRI, and routine EEGs do not usually show epileptiform alterations.

Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.

Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized the impact of plasma lipidome on epilepsy. However, establishing a direct causal link between plasma lipidome and epilepsy remains elusive due to inherent confounders and the complexities of reverse causality. This study aims to investigate the causal relationship between specific plasma lipidome and epilepsy, along with their intermediary mediators. We conducted a two-sample Mendelian randomization (MR) and mediation MR analysis to evaluate the causal effects of 179 plasma lipidomes and epilepsy, with a focus on the inflammatory cytokine as a potential mediator based on the genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by a range of other estimators. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test and leave-one-out sensitivity analyses was performed to assess the robustness, heterogeneity and horizontal pleiotropy of results. Our findings revealed a positive correlation between Phosphatidylcholine (18:1_18:1) levels with epilepsy risk (OR = 1.105, 95% CI: 1.036-1.178, p = 0.002). Notably, our mediation MR results propose Tumor necrosis factor ligand superfamily member 12 levels (TNFSF12) as a mediator of the relationship between Phosphatidylcholine (18,1_18:1) levels and epilepsy risk, explaining a mediation proportion of 4.58% [mediation effect: (b = 0.00455, 95% CI: -0.00120-0.01030), Z = 1.552]. Our research confirms a genetic causal relationship between Phosphatidylcholine (18:1_18:1) levels and epilepsy, emphasizing the potential mediating role of TNFSF12 and provide valuable insights for future clinical investigations into epilepsy.

Potential causal link between dietary intake and epilepsy: a bidirectional and multivariable Mendelian randomization study.

Epilepsy is a common neurological disease, and dietary intake has been suggested as a potential modifiable risk factor. However, the causality of associations between dietary intake and epilepsy remains uncertain. This study aimed to investigate the potential causal relationships between various dietary intakes and epilepsy using Mendelian randomization (MR) analysis. A two-sample MR approach was employed, utilizing genetic variants associated with dietary factors as instrumental variables (IVs). Genome-Wide Association Study (GWAS) summary data on dietary intakes were obtained from the UK Biobank, while data on epilepsy were sourced from the European Bioinformatics Institute. The number of genetic variants used as IVs varied for each dietary factor. Inverse-variance weighted (IVW), weighted median, MR-Egger, and Bayesian weighted MR (BWMR) methods were used to assess causality. Multivariable MR (MVMR) was performed, adjusting for potential confounders. Sensitivity analyses were conducted to evaluate the robustness of the findings. The study identified a significant inverse association between non-oily fish intake and epilepsy risk (OR = 0.281, 95% CI: 0.099-0.801, p = 0.018) using the IVW method. This finding was corroborated by the BWMR analysis (OR = 0.277, 95% CI: 0.094-0.814, p = 0.020). The MVMR analysis further confirmed the protective effect of non-oily fish intake on epilepsy risk after adjusting for potential confounders. In the reverse MR analysis, epilepsy was associated with reduced water intake (OR = 0.989, 95% CI: 0.980-0.997, p = 0.011). The present MR study provides evidence of a causal, protective relationship between non-oily fish intake and reduced epilepsy risk. Additionally, the findings suggest that epilepsy may influence water intake patterns. These results contribute to our understanding of the role of dietary factors in epilepsy and may inform dietary recommendations for the management and prevention of this condition.

Diet-derived circulating antioxidants and risk of epilepsy: a Mendelian randomization study.

Previous studies suggest a link between diet-derived circulating antioxidants and epilepsy, but the causal relationship is unclear. This study aims to investigate the causal effect of these antioxidants on epilepsy. To assess the causal link between dietary antioxidants and epilepsy risk, we conducted a two-sample Mendelian randomization (MR) analysis. This involved examining antioxidants such as zinc, selenium, α- and γ-tocopherol, vitamin A (retinol), vitamin C (ascorbate), and vitamin E (α-tocopherol). We utilized instrumental variables (IVs) which were genetic variations highly associated with these commonly used antioxidants. Exposure data were sourced from a comprehensive genome-wide association study (GWAS). We aggregated data from the International League Against Epilepsy (ILAE) Consortium sample, which included various types of epilepsy, as an outcome variable. Finally, we applied the inverse variance weighting method and conducted sensitivity analyses for further validation. Based on the primary MR estimates and subsequent sensitivity analyses, the inverse variance weighting (IVW) method revealed that a genetically predicted increase in zinc per standard deviation was positively associated with three types of epilepsy. This includes all types of epilepsy (OR = 1.06, 95% CI: 1.02-1.11, p = 0.008), generalized epilepsy (OR = 1.13, 95% CI: 1.01-1.25, p = 0.030), and focal epilepsy (documented hippocampal sclerosis) (OR = 1.01, 95% CI: 1.00-1.02, p = 0.025). However, there is no evidence indicating that other antioxidants obtained from the diet affect the increase of epilepsy either positively or negatively. Our research indicates that the risk of developing epilepsy may be directly linked to the genetic prediction of zinc, whereas no such association was found for other antioxidants.

Impact of Consanguinity on Epilepsy Risk in Al-Jouf, Saudi Arabia: A Hospital-Based Cross-Sectional Study

Impact of Consanguinity on Epilepsy Risk in Al-Jouf, Saudi Arabia: A Hospital-Based Cross-Sectional Study

Ictal Semiology Important for Electrode Implantation and Interpretation of Stereoelectroencephalography.

Scalp video-electroencephalography (video-EEG) monitoring should be analyzed thoroughly to preoperatively evaluate stereoelectroencephalography (SEEG). Formulating the working hypotheses for the epileptogenic zone (EZ) considering "anatomo-electroclinical correlations" is the most crucial step, which determines the placement of SEEG electrodes. If these hypotheses are insufficient, precise EZ identification may not be achieved during SEEG recording.In ictal semiology analysis, temporal and spatial patterns with reference to ictal EEG changes are emphasized. In frontal lobe epilepsy, seizures often begin with relatively widespread synchronous activity, and complex motor symptoms manifest within seconds. Due to the wide area involved and intense interhemispheric connectivity, a comprehensive evaluation is often required. Hypotheses are formulated on the basis of the motor symptoms and emotional manifestations that are related to the prefrontal cortices. In temporal lobe epilepsy, EEG onset often precedes clinical onset. Propagation from the EZ to locations within and outside of the temporal lobe is examined from both the EEG and semiological standpoint. The characteristics of contralateral versive seizures, contralateral tonic seizures, and frequent focal onset bilateral tonic-clonic seizures indicate a higher risk of temporo-perisylvian epilepsy. In parietal/occipital lobe epilepsy, despite that some symptoms result from activity in the immediate vicinity, stronger connectivity with other regions usually contributes to the generation of prominent ictal semiology. Hence, multilobar electrode placement is often useful in practice. For insular epilepsy, it is important to understand the anatomy, function, and networks between other regions. A semiological approach is one of the most important clues for electrode implantation and interpretation of SEEG.

Long-Term Neurological Morbidity Among Children Delivered by Vacuum Extraction—A National Cohort Study

(Abstracted from Acta Obstet Gynecol Scand 2023;102:843–853) Many factors during pregnancy and childbirth influence long term neurological outcomes, but some controllable factors have not been studied extensively; one of these factors is vacuum extraction (VE) as a method of assisted childbirth. This study was designed as the first nationwide cohort study examining VE and its impact on long-term neurological morbidity, and its aim was to assess the risks of neonatal mortality, cerebral palsy (CP), and epilepsy in children delivered by VE.

What is the role of screening instruments in the management of psychiatric comorbidities in epilepsy? Tools and practical tips for the most common comorbidities: Depression and anxiety

Depression and anxiety are the most common psychiatric comorbidities in epilepsy and are known to increase healthcare utilization, the risk of refractory epilepsy, and anti-seizure medication intolerability. Despite this, depression and anxiety continue to be underrecognized and undertreated in people with epilepsy (PWE). Several barriers to the identification of depression and anxiety in PWE exist, including reliance on unstructured interviews rather than standardized, validated instruments. Moreover, there is a dearth of behavioral health providers to manage these comorbidities once identified. The use of validated screening instruments in epilepsy clinics can assist with both the identification of psychiatric symptoms and monitoring of treatment response by the epilepsy clinician for PWE with comorbid depression and/or anxiety. While screening instruments can identify psychiatric symptoms occurring within a specified time, they are not definitively diagnostic. Screeners can be time efficient tools to identify patients requiring further evaluation for diagnostic confirmation.This article reviews recent literature on the utility of depression and anxiety screening instruments in epilepsy care, including commonly used screening instruments, and provides solutions for potential barriers to clinical implementation. Validated depression and anxiety screening instruments can increase identification of depression and anxiety and guide epilepsy clinician management of these comorbidities which has the potential to positively impact patient care.

Type 1 diabetes and the risk of epilepsy: A meta-analysis.

An overrepresentation of epilepsy has been suggested in patients with type 1 diabetes (T1D). This meta-analysis was conducted to evaluate if type 1 diabetes is associated with a higher incidence of epilepsy. Longitudinal observational studies which are relevant to the purpose of the meta-analysis were screened and obtained by searching PubMed, Embase, and Web of Science databases. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. Six observational studies involving 10 datasets of 8,001,899 participants were included, with six datasets including children and only one dataset including older people. Among them, 100,414 (1.25%) had type 1 diabetes. During the follow-up duration of 5.4-15.2 years (mean: 9.5 years), 98,644 cases (1.23%) of epilepsy were observed. Compared with participants with normoglycemia, those with type 1 diabetes were shown to have a higher incidence of epilepsy (risk ratio [RR]: 2.41, 95% confidence interval 1.69-3.44, P < 0.001; I2 = 95%) after adjustment of potential confounding variables including age and sex. Subgroup analysis showed consistent results in nested case-control and retrospective cohort studies, and in studies of children, non-elderly adult, and older participants (P for subgroup difference = 0.42 and 0.07). In addition, a stronger association of type 1 diabetes and epilepsy was suggested in studies with follow-up duration <10 years compared with those ≥10 years (RR: 3.34 vs 1.61, P for subgroup difference < 0.001). Patients with type 1 diabetes may have a higher risk of epilepsy, which was mainly driven by datasets including children.

Electroencephalographic abnormalities in children with type 1 diabetes mellitus: a prospective study.

The aim herein was to investigate epileptiform discharges on electroencephalogram (EEG), their correlation with glutamic acid decarboxylase 65 autoantibody (GAD-ab) in newly diagnosed pediatric type 1 diabetes mellitus (T1DM) patients and interpret their medium-term utility in predicting epilepsy. Children presenting with T1DM between July 2018 and December 2019 were included in this prospective longitudinal study. Patients with a history of head injury, chronic illness, neurological disorder, seizure, autism, or encephalopathy were excluded. EEGs were obtained within the first 7 days of diagnosis and later reviewed by a pediatric neurologist. All of the children were clinically followed-up in pediatric endocrinology and neurology clinics for 2 years after their diagnosis. A total of 105 children (46 male, 43.8%) were included. The mean age at the time of diagnosis was 9.6 ± 4.1 years (range: 11 months-17.5 years). At the time of admission, 24 (22.9%), 29 (27.6%), and 52 (49.5%) patients had hyperglycemia, ketosis, and diabetic ketoacidosis, respectively. GAD-ab was positive in 55 children (52.4%). No background or sleep architecture abnormalities or focal slowing were present on the EEGs. Of the patients, 3 (2.9%) had focal epileptiform discharges. The mean GAD-ab levels of the remaining 102 patients were 7.48 ± 11.97 U/mL (range: 0.01-50.54) (p = 0.2). All 3 children with EEG abnormality had higher levels of GAD-ab (3.59 U/mL, 31.3 U/mL, and 7.09 U/mL, respectively). None of the patients developed epilepsy during the follow-up, although 1 patient experienced Guillain-Barré syndrome (GBS). The prevalence of epileptiform discharges in the patients was similar to those of previous studies, in which healthy children were also included. No relationship was found between the epileptiform discharges and GAD-ab, and none of the patients manifested seizures during the first 2 years of follow-up of T1DM. These data support the findings of previous studies reporting that T1DM patients with confirmed electroencephalographic abnormalities do not have an increased risk of epilepsy. On the other hand, GBS might be considered as another autoimmune disease that may be associated with T1DM in children.

Association Between Dysmenorrhea and Risk of Epilepsy in East Asian Populations: A Bidirectional Two-Sample Mendelian Randomization Study

AbstractDysmenorrhea is associated with epilepsy. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of dysmenorrhea on epilepsy using Mendelian randomization (MR). We extracted instrumental variants for dysmenorrhea and epilepsy from published genomewide association study data, focusing on individuals of East Asian descent. A comprehensive suite of MR estimations and sensitivity analyses was performed to ensure the robustness of the findings. Each outcome database was analyzed separately in both directions. For dysmenorrhea and epilepsy, 7 and 3 genetic variants respectively were selectively extracted as instrumental variants. The results suggest that dysmenorrhea is causally associated with an elevated risk of epilepsy (inverse variance weighted [IVW]: OR = 1.26; 95% CI [1.07, 1.47]; p = 4.42 × 10−3); conversely, no strong evidence was found to corroborate that epilepsy exerts a causal effect on the incidence of dysmenorrhea (IVW: OR = 1.04; 95% CI [0.82, 1.33]; p = .72). These findings provide novel insights into the causal relationship between dysmenorrhea and epilepsy, which may have implications for clinical decision-making in patients with epilepsy and dysmenorrhea.

Risk Factors Associated with Epilepsy Related to Cerebrovascular Disease: A Systematic Review and Meta-Analysis.

Stroke is one of the most frequent neurological syndromes in the adult population and the cause of 10% of all diagnosed epilepsies. It is attributed to the origin of up to 50% of them in adults >60 years of age. Although a few risk factors have been described and considered when modeling predictive tools, this aspect is still clinically complex. The objective of this study is to describe and compare predictor scales of post stroke epilepsy (PSE) in adult patients with better performance. A systematic review and meta-analysis were performed of studies published between 2010 and 2020 and found in PubMed, Scopus, EMBASE, LILACS, BVS, Google Scholar, and CENTRAL databases. Sixteen studies were included with a total of 298,694 patients with a diagnosis of stroke, 5590 presented late seizures (LS). Hemorrhage, cortical involvement, and early seizure were the elements most associated with the risk of presenting late seizures. The SeLECT score demonstrated a low risk of bias with a high predictive ability in patients with ischemic stroke (AUC: 0.77 [95% CI: 0.71-0.82]). In patients with hemorrhagic stroke, the CAVE score demonstrated adequate predictive ability (AUC: 0.81 [95% CI: 0.76-0.86]), but an uncertain risk of bias. Research has established risk factors for post ictal epilepsy; however, the numerous ways of assessing data in studies and the difference in their designs make the task of producing a predictive scale that covers the most important risk factors and is reliable for application in the clinical setting, regardless of stroke etiology, very arduous. Hemorrhage, cortical involvement, and early seizure are associated with an increased risk of post ictal epilepsy. Also, elements such as age, traditional vascular risk factors, and functional assessment failed to reflect statistical significance. Finally, further research is required to refine the available predictive tools.

Risk assessment of long-term epilepsy after de novo status epilepticus with clinical and electroencephalographic biomarkers: The AFTER score

BackgroundThe risk of developing epilepsy after de novo status epilepticus (SE) is nonnegligible. The individualized management of patients with high risk of subsequent epilepsy could improve long-term quality of life and cognitive impairment. We aimed to ascertain potential biomarkers of subsequent epilepsy and to construct a scoring system possessing predictive value for the diagnosis of post-SE epilepsy during follow-up. MethodsThe study data were obtained from a prospective registry of all SE episodes occurring in patients over 16 years attended in our tertiary center from February 2011 to April 2022. Clinical data, electroencephalography findings, treatment, and long-term clinical data were prospectively recorded. We selected SE patients at risk of developing epilepsy (acute symptomatic and cryptogenic etiologies with no previous history of epilepsy) and analyzed the risk of developing subsequent epilepsy. ResultsWe included 230 patients. Median age was 65 years ± 16.9 SD and 112/230 (48.7 %) were women. One-hundred ninety-eight patients (86.1 %) had an acute symptomatic SE, whereas 32 patients (13.9 %) presented with a cryptogenic SE.A total of 55 patients (23.9 %) developed an unprovoked remote seizure and were diagnosed with epilepsy. After adjusting for identifiable confounders in a multivariable Cox regression analysis cryptogenic etiology (HR 2.24 [1.13–4.46], p = 0.022), first-line treatment initiation ≥1 h (HR 2.12 [1.03–4.36], p = 0.041], RDA/LPD/GPD EEG patterns (HR 1.88 [1.07–3.32], p = 0.028), and super-refractoriness (HR 2.90 [1.40–5.99], p = 0.004) emerged as independent predictors of post-SE epilepsy. Based on these findings, we constructed the AFTER score (1 point for each item) with a robust capability to predict post-SE epilepsy at 5 years (AUC 74.3 %, 95 %CI 64.3–84.3 %, p < 0.001). ConclusionsThe AFTER score is a robust predictor of the development of epilepsy after new onset SE using clinical and electroencephalographic biomarkers (such as etiology, time to first-line treatment initiation, EEG pattern and super-refractoriness). Prospective studies are warranted to validate the score in other populations.

Role of Deployment History on the Association Between Epilepsy and Traumatic Brain Injury in Post-9/11 Era US Veterans.

Traumatic brain injury (TBI) is a well-established epilepsy risk factor and is common among service members. Deployment-related TBI, where combat/blast may be more common, may have different outcomes than nondeployment-related TBI. This work examined associations of all TBI exposures (not just combat), and epilepsy, while adjusting for comorbidities associated with epilepsy, among veterans by deployment status. The cohort included post-9/11 veterans with ≥2 years of care in both Veterans Health Administration and Defense Health Agency systems. We identified epilepsy using ICD-9/10-CM codes, antiseizure medication, and service-connected disability for epilepsy. We conducted a logistic regression model with interaction terms for conditions by deployment history that adjusted for demographics and military characteristics. The cohort (n = 938,890) included post-9/11 veterans of whom 27,436 (2.92%) had epilepsy. Most veterans had a history of deployment (70.64%), referred to as "deployed." Epilepsy was more common among veterans who were never deployed ("nondeployed") (3.85% vs 2.54%). Deployed veterans were more likely to have had TBI, compared with the nondeployed veterans (33.94% vs 14.24%), but nondeployed veterans with moderate/severe TBI had higher odds of epilepsy compared with deployed veterans (adjusted odds ratio [aOR] 2.92, 95% CI 2.68-3.17 vs aOR 2.01, 95% CI 1.91-2.11). Penetrating TBI had higher odds of epilepsy among the deployed veterans (aOR 5.33, 95% CI 4.89-5.81), whereas the odds of epilepsy for mild TBI did not significantly differ by deployment status. Although most neurologic conditions were more prevalent among the nondeployed veterans, they were often associated with higher odds of epilepsy in the deployed veterans. Deployment history had a significant differential impact on epilepsy predictors. As expected, penetrating TBI had a greater epilepsy impact among deployed veterans perhaps due to combat/blast. Some epilepsy predictors (moderate/severe TBI, multiple sclerosis, and Parkinson disease) had a stronger association in the nondeployed veterans suggesting a potential healthy warrior effect in which such conditions preclude deployment. Other neurologic conditions (e.g., brain tumor, Alzheimer disease/frontotemporal dementia) had a greater epilepsy impact in the deployed veterans. This may be attributable to deployment-related exposures (combat injury, occupational exposures). A better understanding of deployment effects is critical to provide targeted epilepsy prevention in veterans and military service members.

Mice deficient in complement C3 are protected against recognition memory deficits and astrogliosis induced by status epilepticus.

Status epilepticus (SE) can significantly increase the risk of temporal lobe epilepsy (TLE) and cognitive comorbidities. A potential candidate mechanism underlying memory defects in epilepsy may be the immune complement system. The complement cascade, part of the innate immune system, modulates inflammatory and phagocytosis signaling, and has been shown to contribute to learning and memory dysfunctions in neurodegenerative disorders. We previously reported that complement C3 is elevated in brain biopsies from human drug-resistant epilepsy and in experimental rodent models. We also found that SE-induced increases in hippocampal C3 levels paralleled the development of hippocampal-dependent spatial learning and memory deficits in rats. Thus, we hypothesized that SE-induced C3 activation contributes to this pathophysiology in a mouse model of SE and acquired TLE. In this study C3 knockout (KO) and wild type (WT) mice were subjected to one hour of pilocarpine-induced SE or sham conditions (control; C). Following a latent period of two weeks, recognition memory was assessed utilizing the novel object recognition (NOR) test. Western blotting was utilized to determine the protein levels of C3 in hippocampal lysates. In addition, we assessed the protein levels and distribution of the astrocyte marker glial fibrillary acidic protein (GFAP). In the NOR test, control WT + C or C3 KO + C mice spent significantly more time exploring the novel object compared to the familiar object. In contrast, WT+SE mice did not show preference for either object, indicating a memory defect. This deficit was prevented in C3 KO + SE mice, which performed similarly to controls. In addition, we found that SE triggered significant increases in the protein levels of GFAP in hippocampi of WT mice but not in C3 KO mice. These findings suggest that ablation of C3 prevents SE-induced recognition memory deficits and that a C3-astrocyte interplay may play a role. Therefore, it is possible that enhanced C3 signaling contributes to SE-associated cognitive decline during epileptogenesis and may serve as a potential therapeutic target for treating cognitive comorbidities in acquired TLE.

Exome analysis focusing on epilepsy-related genes in children and adults with sudden unexplained death

PurposeGenetic studies in sudden infant death syndrome (SIDS) and sudden unexplained death (SUD) cohorts have indicated that cardiovascular diseases might have contributed to sudden unexpected death in 20–35 % of autopsy-negative cases. Sudden unexpected death can also occur in people with epilepsy, termed as sudden unexpected death in epilepsy (SUDEP). The pathophysiological mechanisms of SUDEP are not well understood, but are likely multifactorial, including seizure-induced hypoventilation and arrhythmias as well as genetic risk factors. The sudden death of some of the SIDS/SUD victims might also be explained by genetic epilepsy, therefore this study aimed to expand the post-mortem genetic analysis of SIDS/SUD cases to epilepsy-related genes. MethodsExisting whole-exome sequencing data from our 155 SIDS and 45 SUD cases were analyzed, with a focus on 365 epilepsy-related genes. Nine of the SUD victims had a known medical history of epilepsy, seizures or other underlying neurological conditions and were therefore classified as SUDEP cases. ResultsIn our SIDS and SUD cohorts, we found epilepsy-related pathogenic/likely pathogenic variants in the genes OPA1, RAI1, SCN3A, SCN5A and TSC2. ConclusionPost-mortem analysis of epilepsy-related genes identified potentially disease-causing variants that might have contributed to the sudden death events in our SIDS/SUD cases. However, the interpretation of identified variants remains challenging and often changes over time as more data is gathered. Overall, this study contributes insight in potentially pathophysiological epilepsy-related mechanisms in SIDS, SUD and SUDEP victims and underlines the importance of sensible counselling on the risk and preventive measures in genetic epilepsy.

39 Neurodevelopmental Complexity of a Patient with Perinatal Right Middle Cerebral Artery Stroke and Infantile Spasms

Objective:A rich literature exists on cognitive changes related to focal injury in the adult brain. In contrast, the developing brains of children are less understood. In contrast to adult cases, 20% to 25% of perinatal strokes result in language disorder regardless of lesion lateralization. Existing literature suggests children with perinatal stroke may present with a range of executive functioning and visuospatial processing difficulties. Gross and fine motor challenges are also likely to occur. Furthermore, these children have an increased prevalence of autism spectrum disorder (ASD) and carry the highest risk for epilepsy. Despite growing research on neurodevelopmental profiles in patients with perinatal stroke, published literature is limited.Participants and Methods:Our study examines neurodevelopment of a 2-year-old, right-handed male with a history of perinatal ischemic right middle cerebral artery (MCA) stroke, infantile spasms, and left hemiparesis following right hemispherectomy for seizure management who underwent two neurodevelopmental evaluations at our medical center over approximately 3 years.Results:Findings from the patient’s evaluation with the Mullen Scales of Early Learning revealed overall cognitive ability in the low average range (SS = 89, 23rd percentile); however, notable variability was seen in his performance. His receptive language was average (SS = 98, 45th %tile) and consistent with previous evaluation results, and he has made gains in visual reception (from SS = 75, 5th %tile to SS = 91, 27th %tile) and expressive language (from SS = 55, 0.1st %tile to SS = 70, 2nd %tile). In addition, his gross motor was exceptionally low (SS = 55, 0.1st %tile) and consistent with previous evaluation results. Fine motor was low average (SS = 84, 14th %tile).Conclusions:Our patient showed cognitive gains in language and visual reception since his prior evaluation despite history of right MCA stroke and right hemispherectomy. Improvements are likely due to a combination of early brain plasticity and intensive therapies he has received. Consistent with published findings in this population, he experienced seizures associated with his stroke. Our results add to the limited literature on neurodevelopmental challenges associated with perinatal stroke and progress that can be made when appropriate supports are provided early and consistently.

Prevalence of genetic polymorphisms ABCB1/ C3435T in patients with epilepsy in Iranian population

Introduction: Epilepsy is a common neurological disorder affecting approximately 1% of the global population. A significant proportion of patients develop drug-resistant epilepsy (DRE), which leads to poor outcomes for treatments and low quality of life. The multidrug transporter P-glycoprotein, encoded by the ABCB1 gene, plays a key role in limiting brain penetration of antiepileptic drugs. The C3435T single nucleotide polymorphism (SNP) in ABCB1 has been linked to variable P-glycoprotein expression and AED response. In this study, the prevalence of C3435T genotypes among epilepsy patients and healthy controls in Fars Province, Iran was investigated. Materials and methods: This study involved 50 patients diagnosed with epilepsy and 100 healthy individuals without a history of seizures or epilepsy. Genotyping was conducted using PCR-RFLP analysis. Results: The variant T allele occurred at a frequency of 52% in cases and 54% in controls. However, no significant association between the C3435T polymorphism and epilepsy risk was observed. Interestingly, it was found that the CT genotype was overrepresented in drug-responsive patients compared to those with drug-resistant cases. This suggests that individuals with the CT genotype may have a more favorable response to antiepileptic drug therapy. Conclusion: These findings suggest that the ABCB1 C3435T variant may play a role in influencing seizure control specifically among Iranian patients, but its effects on susceptibility are minimal. Moreover, individuals with the CT genotype may have a more favorable response to antiepileptic drug therapy. Further research involving larger cohorts is needed to fully understand the impact of ABCB1 genetics on determining individual responses to antiepileptic drugs. Such research could also pave the way for personalized management strategies based on pharmacogenomic testing.

Association Between Pediatric Traumatic Brain Injury and Epilepsy at Later Ages in Finland - a Nationwide Register-based Cohort Study.

To examine how pediatric traumatic brain injury (pTBI) correlated with incidence of epilepsy at later ages in Finland. A nationwide retrospective register-based cohort study from 1998 to 2018. The study group consisted of 71 969 pediatric (<18 years) patients hospitalized with TBI and a control group consisting of 64 856 pediatric patients with distal extremity fracture. Epilepsy diagnoses were gathered from the Finnish Social Insurance Institution. Kaplan-Meier (KM) and multivariable Cox regression models were conducted to analyze the probability of epilepsy with 95% confidence intervals (CI). Cumulative incidence rates (CIR) for the first 2 years were 0.5% in the pTBI group and 0.1% in the control group. The corresponding rates after 15 years of follow-up were 1.5% in the pTBI group and 0.7% in the control group. Due to proportional hazard (PH) violations, the study population was split to the first 2 years and in subgroup analysis 4 years. During the first 2 years of surveillance, the hazard ratio (HR) for the pTBI group was 4.38 (CI: 3.39-5.66). However, between years 2 and 20, the HR for the pTBI group was 2.02 (CI: 1.71-2.38). A total of 337 patients (0.47%) underwent neurosurgery and 36 (10.7%) patients subsequently developed epilepsy. The CIR for the first year after TBI were 4.5% (CI: 2.3-6.7%) in operatively managed patients and 0.3% (CI: 0.3-0.4%) in non-operatively managed patients. Corresponding figures after 15 years were 12.0% (CI: 8.2-15.8%) and 1.5% (CI: 1.4-1.6%). During the first 4 years of surveillance, the HR for the operative pTBI group was 14.37 (CI: 9.29-20.80) and 3.67 (CI: 1.63-8.22) between years 4 and 20. pTBI exposes patients to a higher risk for posttraumatic epilepsy (PTE) for many years after initial trauma. Children who undergo operative management for TBI have a high risk for epilepsy, and this risk was highest during the first 4 years after injury.

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.