Risk Of Epilepsy Research Articles

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Type of acute symptomatic seizure. All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Risk factors for drug-resistant epilepsy in adult patients

IntroductionDrug-resistant epilepsy occurs in about 30% of epilepsy patients. It has been suggested that etiology or seizure type would increase the risk of pharmacoresistance. This study aims to compare the characteristics of patients with drug-sensitive epilepsy with patients with drug-resistant epilepsy to identify risk factors. Patient and methodsA multicentric cohort study was conducted between 2019 and 2022. We included patients >18 years-old with epilepsy but excluded psychogenic non-epileptic seizures and less than 2 years of follow-up. ResultsWe included 128 patients, of whom 46 had drug-resistance epilepsy, and 82 responding to medication. Both groups showed similar characteristics. Febrile seizures (OR: 7.25), focal epilepsy (OR: 2.4), focal seizures with loss of consciousness (OR: 2.36), structural etiology (OR: 2.2) and abnormal MRI (OR: 4.6) were significant risk factors for drug-resistance epilepsy. ConclusionFollowing other studies, we observed that factors such as epilepsy type, seizure type, structural etiology, abnormal MRI, and febrile seizure increased the risk for drug-resistance epilepsy, in our population.

Mortality risk in adults with intellectual disabilities and epilepsy: an England and Wales case-control study.

People with epilepsy (PWE) and people with intellectual disabilities (ID) both live shorter lives than the general population and both conditions increase the risk of death further. We aimed to measure associations between certain risk factors for death in PWE and ID. A retrospective case-control study was conducted in ten regions in England and Wales. Data were collected on PWE registered with secondary care ID and neurology services between 2017 and 2021. Prevalence rates of neurodevelopmental, psychiatric and medical diagnoses, seizure frequency, psychotropic and antiseizure medications (ASM) prescribed, and health activity (epilepsy reviews/risk assessments/care plans/compliance etc.) recorded were compared between the two groups. 190 PWE and ID who died were compared with 910 living controls. People who died were less likely to have had an epilepsy risk assessment but had a greater prevalence of genetic conditions, older age, poor physical health, generalized tonic-clonic seizures, polypharmacy (not ASMs) and antipsychotic use. The multivariable logistic regression for risk of epilepsy-related death identified that age over 50, medical condition prevalence, antipsychotic medication use and the lack of an epilepsy review in the last 12months as associated with increased risk of death. Reviews by psychiatrists in ID services was associated with a 72% reduction in the odds of death compared neurology services. Polypharmacy and use of antipsychotics may be associated with death but not ASMs. Greater and closer monitoring by creating capable health communities may reduce the risk of death. ID services maybe more likely to provide this holistic approach.

Long-term neurological morbidity among children delivered by vacuum extraction - a national cohort study.

This is the first nationwide cohort study of vacuum extraction (VE) and long-term neurological morbidity. We hypothesized that VE per se, and not only complicated labor, can cause intracranial bleedings, which could further cause neurological long-term morbidity. The aim of this study was to investigate the risk of neonatal mortality, cerebral palsy (CP), and epilepsy among children delivered by VE in a long-term perspective. The study population included 1 509 589 term singleton children planned for vaginal birth in Sweden (January 1, 1999 to December 31, 2017). We investigated the risk of neonatal death (ND), CP, and epilepsy among children delivered by VE (successful or failed) and compared their risks with those born by spontaneous vaginal birth and emergency cesarean section (ECS). We used logistic regression to study the adjusted associations with each outcome. The follow-up time was from birth until December 31, 2019. The percentage and total number of children with the outcomes were ND (0.04%, n = 616), CP (0.12%, n = 1822), and epilepsy (0.74%, n = 11 190). Compared with children delivered by ECS, those born by VE had no increased risk of ND, but there was an increased risk for those born after failed VE (adj OR 2.23 [1.33-3.72]). The risk of CP was similar among children born by VE and those born spontaneously vaginally. Further, the risk of CP was similar among children born after failed VE compared with ECS. The risk of epilepsy was not increased among children born by VE (successful/failed), compared with those who had spontaneous vaginal birth or ECS. The outcomes ND, CP, and epilepsy are rare. In this nationwide cohort study, children born after successful VE had no increased risk of ND, CP or epilepsy compared with those delivered by ECS, but there was an increased risk of ND among those born by failed VE. Concerning the studied outcomes, VE appears to be a safe obstetric intervention; however, it requires a thorough risk assessment and awareness of when to convert to ECS.

In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study.

Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC). We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011-17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)]. In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.

Association of Early Seizure Prophylaxis With Posttraumatic Seizures and Mortality: A Meta-analysis With Evidence Quality Assessment.

To evaluate the quality of evidence about the association of primary seizure prophylaxis with antiseizure medication (ASM) within 7 days postinjury and the 18- or 24-month epilepsy/late seizure risk or all-cause mortality in adults with new-onset traumatic brain injury (TBI), in addition to early seizure risk. Twenty-three studies met the inclusion criteria (7 randomized and 16 nonrandomized studies). We analyzed 9,202 patients, including 4,390 in the exposed group and 4,812 in the unexposed group (894 in placebo and 3,918 in no ASM groups). There was a moderate to serious bias risk based on our assessment. Within the limitations of existing studies, our data revealed a lower risk for early seizures in the ASM prophylaxis group compared with placebo or no ASM prophylaxis (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.33-0.57, p < 0.00001, I 2 = 3%). We identified high-quality evidence in favor of acute, short-term primary ASM use to prevent early seizures. Early ASM prophylaxis was not associated with a substantial difference in the 18- or 24-month risk of epilepsy/late seizures (RR 1.01, 95% CI 0.61-1.68, p = 0.96, I 2 = 63%) or mortality (RR 1.16, 95% CI 0.89-1.51, p = 0.26, I 2 = 0%). There was no evidence of strong publication bias for each main outcome. The overall quality of evidence was low and moderate for post-TBI epilepsy risk and all-cause mortality, respectively. Our data suggest that the evidence showing no association between early ASM use and 18- or 24-month epilepsy risk in adults with new-onset TBI was of low quality. The analysis indicated a moderate quality for the evidence showing no effect on all-cause mortality. Therefore, higher-quality evidence is needed as a supplement for stronger recommendations.

Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy.

Single-nucleotide polymorphisms are connected with the risk of epilepsy on occurrence, progress, and the individual response to drugs. Progress in genomic technology is exposing the complex genetic architecture of epilepsy. Compelling evidence has demonstrated that purines and adenosine are key mediators in the epileptic process. Our previous study found the interconnection of P2Y12 receptor single-nucleotide polymorphisms and epilepsy. However, little is known about the interaction between the purine nucleoside A2A receptor and rate-limiting enzyme ecto-5'-nucleotidase/CD73 and epilepsy from the genetic polymorphism aspect. The aim of the study is to evaluate the impact of A2AR and CD73 polymorphisms on epilepsy cases. The study group encompassed 181 patients with epilepsy and 55 healthy volunteers. A significant correlation was confirmed between CD73 rs4431401 and epilepsy (p < 0.001), with TT genotype frequency being higher and C allele being lower among epilepsy patients in comparison with healthy individuals, indicating that the presence of the TT genotype is related to an increased risk of epilepsy (OR = 2.742, p = 0.006) while carriers of the C allele demonstrated a decreased risk of epilepsy (OR = 0.304, p < 0.001). According to analysis based on gender, the allele and genotype of rs4431401 in CD73 were associated with both male and female cases (p < 0.0001, p = 0.026, respectively). Of note, we found that A2AR genetic variants rs2267076T>C (p = 0.031), rs2298383C>T (p = 0.045), rs4822492T>G (p = 0.034), and rs4822489T>G (p = 0.029) were only associated with epilepsy in female subjects instead of male. It is evident that the TT genotype and T allele of rs4431401 in CD73 were genetic risk factors for epilepsy, whereas rs2267076, rs2298383, rs4822492, and rs4822489 polymorphisms of the A2AR were mainly associated with female subjects.

Factors associated with the development of epilepsy in very low birth weight infants

The survival rate of very low birth weight (VLBW) infants has recently improved. However, the occurrence of and factors associated with epilepsy in VLBW infants remain unknown. This study aimed to clarify the incidence, characteristics, and factors associated with epilepsy development in VLBW infants. All VLBW infants admitted to our hospital between 2012 and 2017 were included in this study. VLBW infants with a follow-up period of <1 year were excluded. Chromosomal abnormalities, brain anomalies, severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and hypoxic ischemic encephalopathy (HIE) were considered to be risk factors. Epilepsy occurred in 21/526 (4.0%) VLBW infants. Chromosomal abnormalities, brain anomalies, severe IVH, cystic PVL, HIE, neonatal seizures, advanced maternal age, maternal diabetes mellitus, no administration of antenatal corticosteroids, and low Apgar scores at 1 and 5min were associated with a risk of epilepsy. The median time to epilepsy onset was 8 months (range: 0-59 months), and the onset occurred within 2 years in 15/21 patients (71.4%) and within 4 years in 18/21 patients (85.7%). VLBW infants with risk factors developed epilepsy earlier and at a significantly higher rate than those without risk factors. Among infants who had risk factors and who developed epilepsy, 86.7% did so within 2 years of age, compared to 33.3% of those who developed epilepsy but did not have risk factors. These findings regarding factors associated with a risk of development of epilepsy and temporal feature of epilepsy may contribute to the development of monitoring and treatment protocols for epilepsy in VLBW infants.

Association of Dementia Risk With Focal Epilepsy and Modifiable Cardiovascular Risk Factors

Epilepsy has been associated with cognitive impairment and potentially dementia in older individuals. However, the extent to which epilepsy may increase dementia risk, how this compares with other neurological conditions, and how modifiable cardiovascular risk factors may affect this risk remain unclear. To compare the differential risks of subsequent dementia for focal epilepsy compared with stroke and migraine as well as healthy controls, stratified by cardiovascular risk. This cross-sectional study is based on data from the UK Biobank, a population-based cohort of more than 500 000 participants aged 38 to 72 years who underwent physiological measurements and cognitive testing and provided biological samples at 1 of 22 centers across the United Kingdom. Participants were eligible for this study if they were without dementia at baseline and had clinical data pertaining to a history of focal epilepsy, stroke, or migraine. The baseline assessment was performed from 2006 to 2010, and participants were followed up until 2021. Mutually exclusive groups of participants with epilepsy, stroke, and migraine at baseline assessment and controls (who had none of these conditions). Individuals were divided into low, moderate, or high cardiovascular risk groups based on factors that included waist to hip ratio, history of hypertension, hypercholesterolemia, diabetes, and smoking pack-years. Incident all-cause dementia; measures of executive function; and brain total hippocampal, gray matter, and white matter hyperintensity volumes. Of 495 149 participants (225 481 [45.5%] men; mean [SD] age, 57.5 [8.1] years), 3864 had a diagnosis of focal epilepsy only, 6397 had a history of stroke only, and 14 518 had migraine only. Executive function was comparable between participants with epilepsy and stroke and worse than the control and migraine group. Focal epilepsy was associated with a higher risk of developing dementia (hazard ratio [HR], 4.02; 95% CI, 3.45 to 4.68; P < .001), compared with stroke (HR, 2.56; 95% CI, 2.28 to 2.87; P < .001), or migraine (HR, 1.02; 95% CI, 0.85 to 1.21; P = .94). Participants with focal epilepsy and high cardiovascular risk were more than 13 times more likely to develop dementia (HR, 13.66; 95% CI, 10.61 to 17.60; P < .001) compared with controls with low cardiovascular risk. The imaging subsample included 42 353 participants. Focal epilepsy was associated with lower hippocampal volume (mean difference, -0.17; 95% CI, -0.02 to -0.32; t = -2.18; P = .03) and lower total gray matter volume (mean difference, -0.33; 95% CI, -0.18 to -0.48; t = -4.29; P < .001) compared with controls. There was no significant difference in white matter hyperintensity volume (mean difference, 0.10; 95% CI, -0.07 to 0.26; t = 1.14; P = .26). In this study, focal epilepsy was associated with a significant risk of developing dementia, to a greater extent than stroke, which was magnified substantially in individuals with high cardiovascular risk. Further findings suggest that targeting modifiable cardiovascular risk factors may be an effective intervention to reduce dementia risk in individuals with epilepsy.

Causal effects of circulating lipids and lipid-lowering drugs on the risk of epilepsy: a two-sample Mendelian randomization study.

Previous studies have reported inconsistent results on the association between circulating lipids and lipid-lowering drugs with the risk of epilepsy. To assess whether genetically predicted circulating lipids and lipid-lowering drugs are causally associated with the risk of epilepsy outcome. We performed a two-sample Mendelian randomization (MR) analysis model to genetically predict the causal effects of circulating lipids (apolipoprotein A [APOA], apolipoprotein B [APOB], cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], lipoprotein A and triglycerides) and lipid-lowering drugs (HMG-CoA reductase [HMGCR] and proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) on epilepsy. Nine MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (simple mode, weighted mode, simple median, weighted median, penalized weighted median, MR Egger and MR-Egger [bootstrap]) were conducted as the complement to IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis. The IVW analysis method demonstrated that there is no causal association between circulating lipids (APOA: odds ratio [OR], 0.958, 95% confidence interval (CI), 0.728-1.261, P = 0.760; APOB: OR, 1.092; 95% CI, 0.979-1.219, P = 0.115; cholesterol: OR, 1.210; 95% CI, 0.981-1.494, P = 0.077; HDL-C: OR, 0.964; 95% CI, 0.767-1.212, P = 0.753; LDL-C: OR, 1.100; 95% CI, 0.970-1.248, P = 0.137; lipoprotein A: OR, 1.082; 95% CI, 0.849-1.379, P = 0.528; triglycerides: OR, 1.126; 95% CI, 0.932-1.360, P = 0.221) and lipid-lowering drugs (HMGCR inhibitors: OR, 0.221; 95% CI, 0.006-8.408, P = 0.878; PCSK9 inhibitors: OR, 1.112; 95% CI, 0.215-5.761, P = 0.902) with risk of epilepsy. The other MR analysis methods and further leave-one-out sensitivity analysis confirmed the robustness of final results. This MR study demonstrated that there were no genetically predicted causal relationships between circulating lipids and lipid-lowering drugs with the risk of epilepsy.

Unexpected cardiorespiratory findings postictally and at rest weeks prior to SUDEP.

Mechanisms underlying sudden unexpected death in epilepsy (SUDEP) are unclear, but autonomic disorders are thought to play a critical role. However, those dysfunctions have mainly been reported in the peri-ictal context of generalized tonic-clonic seizures. Here, we explored whether heart rate variability (HRV), heart rate (HR), and breathing rate (BR) changes could be observed perictally during focal seizures with or without impaired awareness as well as interictally to assess the risk of SUDEP. We report the case of a 33-year-old patient with drug-resistant bilateral temporal lobe epilepsy who died at home probably from an unwitnessed nocturnal seizure ("probable SUDEP"). Ictal and interictal HRV as well as postictal cardiorespiratory analyses were conducted to assess autonomic functions and overall SUDEP risk. The SUDEP patient was compared to two living male patients from our local database matched for age, sex, and location of the epileptic focus. Interictal HRV analysis showed that all sleep HRV parameters and most awake HRV parameters of the SUDEP patient were significantly lower than those of our two control subjects with bitemporal lobe epilepsy without SUDEP (p < 0.01). In two focal with impaired awareness seizures (FIAS) of the SUDEP patient, increased postictal mean HR and reduced preictal mean high frequency signals (HF), known markers of increased seizure severity in convulsive seizures, were seen postictally. Furthermore, important autonomic instability and hypersensitivity were seen through fluctuations in LF/HF ratio following two seizures of the SUDEP patient, with a rapid transition between sympathetic and parasympathetic activity. In addition, a combination of severe hypopnea (202 s) and bradycardia (10 s), illustrating autonomic dysfunction, was found after one of the SUDEP patient's FIAS. The unusual cardiorespiratory and HRV patterns found in this case indicated autonomic abnormalities that were possibly predictive of an increased risk of SUDEP. It will be interesting to perform similar analyses in other SUDEP cases to see whether our findings are anecdotal or instead suggestive of reliable biomarkers of high SUDEP risk in focal epilepsy, in particular focal with or without impaired awareness seizures.

GCP16 stabilizes the DHHC9 subfamily of protein acyltransferases through a conserved C-terminal cysteine motif.

Protein S-acylation is a reversible lipid post-translational modification that allows dynamic regulation of processes such as protein stability, membrane association, and localization. Palmitoyltransferase ZDHHC9 (DHHC9) is one of the 23 human DHHC acyltransferases that catalyze protein S-acylation. Dysregulation of DHHC9 is associated with X-linked intellectual disability and increased epilepsy risk. Interestingly, activation of DHHC9 requires an accessory protein-GCP16. However, the exact role of GCP16 and the prevalence of a requirement for accessory proteins among other DHHC proteins remain unclear. Here, we report that one role of GCP16 is to stabilize DHHC9 by preventing its aggregation through formation of a protein complex. Using a combination of size-exclusion chromatography and palmitoyl acyltransferase assays, we demonstrate that only properly folded DHHC9-GCP16 complex is enzymatically active in vitro. Additionally, the ZDHHC9 mutations linked to X-linked intellectual disability result in reduced protein stability and DHHC9-GCP16 complex formation. Notably, we discovered that the C-terminal cysteine motif (CCM) that is conserved among the DHHC9 subfamily (DHHC14, -18, -5, and -8) is required for DHHC9 and GCP16 complex formation and activity in vitro. Co-expression of GCP16 with DHHCs containing the CCM improves DHHC protein stability. Like DHHC9, DHHC14 and DHHC18 require GCP16 for their enzymatic activity. Furthermore, GOLGA7B, an accessory protein with 75% sequence identity to GCP16, improves protein stability of DHHC5 and DHHC8, but not the other members of the DHHC9 subfamily, suggesting selectivity in accessory protein interactions. Our study supports a broader role for GCP16 and GOLGA7B in the function of human DHHCs.

The effect of age at onset of type 1 diabetes mellitus on epilepsy vulnerability

AimsTo examine whether type 1 diabetes age onset correlates with epilepsy incidence. MethodsWe used type 1 diabetes longitudinal data with onset age ≤ 40 years enrolled in Taiwan National Health Insurance program to examine type 1 diabetes onset age effect on epilepsy occurrence. ResultsIn 6,165 type 1 diabetes patients, onset age groups included 3,571 patients (58%) ≤ 18 years (childhood-onset) and 2,594 patients (42%) > 18 years (adulthood-onset). After 8.6 years median follow-up following type 1 diabetes onset, epilepsy incidence rate in adulthood-onset group was 2.26-fold higher than that in childhood-onset group. Epilepsy incidence rate ratio was lowest in those with onset age 6–12 years in comparison to that in patients with onset age ≤ 6 years, but was highest in onset age of 30–40 years. Longer follow-up duration correlates with higher epilepsy risk in adulthood-onset group. Multiple logistic regression analysis showed that onset age 30–40 years, male, more than one diabetic ketoacidosis episode, and unprovoked seizure events were independent risk factors for epilepsy following type 1 diabetes onset. ConclusionsThere is age-related vulnerability to epilepsy following type 1 diabetes onset. Adulthood-onset type 1 diabetes is an independent risk factor for epilepsy susceptibility after type 1 diabetes.

Epileptiform activity in the acute phase of stroke predicts the outcomes in patients without seizures.

The abnormalities in EEG of stroke-patients increase the risk of epilepsy but their significancy for poststroke outcome is unclear. This presented study was aimed at determining the prevalence and nature of changes in EEG recordings from the stroke hemisphere and from the contralateral hemisphere. Another objective was to determine the significance of abnormalities in EEG in the first days of stroke for the post-stroke functional status on the acute and chronic phase of disease. In all qualified stroke-patients, EEG was performed during the first 3 days of hospitalization and at discharge. The correlation between EEG abnormalities both in the stroke hemisphere and in the collateral hemisphere with the neurological and functional state in various time points was performed. One hundred thirty-one patients were enrolled to this study. Fifty-eight patients (44.27%) had abnormal EEG. The sporadic discharges and generalized rhythmic delta activity were the most common abnormalities in the EEG. The neurological status on the first day and the absence of changes in the EEG in the hemisphere without stroke were the independent factors for good neurological state (0-2 mRS) at discharge. The age-based analysis model (OR 0.981 CI 95% 0.959-1.001, p = 0.047), neurological status on day 1 (OR 0.884 CI 95% 0.82-0.942, p < 0.0001) and EEG recording above the healthy hemisphere (OR 0.607 CI 95% 0.37-0.917, p = 0.028) had the highest prognostic value in terms of achieving good status 90 days after stroke. Abnormalities in EEG without clinical manifestation are present in 40% of patients with acute stroke. Changes in EEG in acute stroke are associated with a poor neurological status in the first days and poor functional status in the chronic period of stroke.

Retracted Article: Relationship Between Multiple Sclerosis and Spiritual Distress

Multiple sclerosis (MS) is the prototype inflammatory autoimmune disorder of the central nervous system and potentially the most common cause of neurological disability in young adults.[1] Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy.[2] MS remains a difficult disease for which solutions seem attainable yet remain elusive.[1] The identified risk factors for MS are low vitamin D levels, a history of Epstein–Barr virus, smoking, and obesity, especially during childhood. On the other hand, complex interactions between genetic, environmental, and lifestyle factors affect the risk for MS as well as the disease course.[3] Factors proposed as potential moderators and mediators between stress and MS include stressor properties, environmental factors, and patients' biological, social, and psychological characteristics.[4] Spiritual distress is defined as “a disruption in the life principle that pervades a person's entire being and that integrates and transcends one's biological and psychological nature.”[5] Herein, we discussed the relationship between MS and spiritual distress to attract attention to the possible role of spiritual distress in patients with MS.

Causal relationship between human blood omega-3 fatty acids and the risk of epilepsy: A two-sample Mendelian randomization study.

Though omega-3 fatty acids reduce seizures in several animal models, considerable controversy exists regarding the association between omega-3 fatty acids and epilepsy in human. To assess whether genetically determined human blood omega-3 fatty acids are causally associated with the risk of epilepsy outcomes. We conducted a two-sample Mendelian randomization (MR) analysis by applying summary statistics of genome-wide association study datasets of both exposure and outcomes. Single nucleotide polymorphisms significantly associated with blood omega-3 fatty acids levels were selected as instrumental variables to estimate the causal effects on epilepsy. Five MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR-Egger, weighted median, simple mode, and weighted mode) were conducted as the complement to IVW. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. Genetically predicted the increase of human blood omega-3 fatty acids levels was associated with a higher risk of epilepsy (OR = 1.160, 95%CI = 1.051-1.279, P = 0.003). This study revealed a causal relationship between blood omega-3 fatty acids and the risk of epilepsy, thus providing novel insights into the development mechanism of epilepsy.

Distinct genetic basis of common epilepsies and structural magnetic resonance imaging measures.

Focal and generalized epilepsies are associated with robust differences in magnetic resonance imaging (MRI) measures of subcortical structures, gray matter, and white matter. However, it is unknown whether such structural brain differences reflect the cause or consequence of epilepsy or its treatment. Analyses of common genetic variants underlying both common epilepsy risk and variability in structural brain measures can give further insights, as such inherited variants are not influenced by disease or treatment. Here, we performed genetic correlation analyses using data from the largest genome-wide association study (GWAS) on common epilepsy (n= 27 559 cases and 42 436 controls) and GWASs on MRI measures of white (n= 33 292) or gray matter (n= 51 665). We did not detect any significant genetic correlation between any type of common epilepsy and any of 280 measures of gray matter, white matter, or subcortical structures. These results suggest that there are distinct genetic bases underlying risk of common epilepsy and for structural brain measures. This would imply that the genetic basis of normal structural brain variation is unrelated to that of common epilepsy. Structural changes in epilepsy could rather be the consequence of epilepsy, its comorbidities, or its treatment, offering a cumulative record of disease.

Causal effect of psychiatric disorders on epilepsy: A two-sample Mendelian randomization study.

This study aims to explore the relationship between psychiatric disorders and the risk of epilepsy using Mendelian randomization (MR) analysis. We collected summary statistics of seven psychiatric traits from recent largest genome-wide association study (GWAS), including major depressive disorder (MDD), anxiety disorder, autism spectrum disorder (ASD), bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), and insomnia. Then, MR analysis estimates were performed based on International League Against Epilepsy (ILAE) consortium data (ncase =15,212 and ncontrol =29,677), the results of which were subsequently validated in FinnGen consortium (ncase =6260 and ncontrol =176,107). Finally, a meta-analysis was conducted based on the ILAE and FinnGen data. We found significant causal effects of MDD and ADHD on epilepsy in the meta-analysis of the ILAE and FinnGen, with corresponding odds ratios (OR) of 1.20 (95% CI 1.08-1.34, p=.001) and 1.08 (95% CI 1.01-1.16, p=.020) by the inverse-variance weighted (IVW) method respectively. MDD increases the risk of focal epilepsy while ADHD has a risk effect on generalized epilepsy. No reliable evidence regarding causal effects of other psychiatric traits on epilepsy was identified. This study suggests that major depressive disorder and attention deficit hyperactivity disorder may causally increase the risk of epilepsy.

Suicide risk in epilepsy: Clinical variables, psychiatric disorders, and social support.

To explore the relationship between suicide risk, the perception of social support and quality of life (QoL), and with the clinical variables of adult people with epilepsy (PWEs). A total of 98 consecutive PWEs cared for in the outpatient setting, with a mean age of 48.1±15.9 years, having had epilepsy for 26.4±16.4 years and 48 (48.9%) female cases participated in this study. The MINI suicide module, the Social support satisfaction scale (SSSS), the Quality of life in epilepsy inventory (QOLIE-31), and the Hospital anxiety and depression scale (HADS) were used. A logistic regression was conducted to assess the factors associated with the suicide risk. Suicide risk was present in 33 cases. Younger age, earlier age at epilepsy onset, depression and anxiety in the HADS scale, and lower MMSE, QOLIE-31, and SSSS scores were significantly associated with suicide risk in the univariate analysis. The logistic regression analysis identified that lower scores in the MMSE (OR 0.826, 95%CI 0.705-0.969), presence of anxiety (OR 0.197, CI 0.073-0.530), and a low perception regarding satisfaction with family (OR 0.953, CI 0.920-0.988) are the factors associated with the highest risk of suicide. Suicide risk and recurrence of a suicide attempt was high in the PWEs. Suicide risk was associated with clinical variables, the presence of anxiety and the perception of less social support from the family.

Roles of gut microbiome in epilepsy risk: A Mendelian randomization study.

Recent studies have suggested an association between gut microbiomes (GMs) and epilepsy. However, the GM taxa identified in different studies are variable. In addition, observational studies cannot indicate causality. Therefore, our study aimed to explore the causal association of GMs with epilepsy and identify the most influential GM taxa. We conducted a Mendelian randomization (MR) study using summary statistics from genome-wide association studies (GWAS) of 211 GM taxa and epilepsy. The GWAS summary statistics for 211 GM taxa (from phylum to genus level) were generated by the MiBioGen consortium, while the FinnGen consortium provided the GWAS summary statistics for epilepsy. The primary analytical method to assess causality was the inverse-variance weighted (IVW) approach. To complement the IVW method, we also applied four additional MR methods: MR-Egger, weighted median, simple mode, and weighted. In addition, we conducted sensitivity analyses using Cochrane's Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. We evaluated the causal effect of 211 GM taxa (from phylum to genus level) on epilepsy, generalized epilepsy, and focal epilepsy. After using the Bonferroni method for multiple testing correction, Class Betaproteobacteria [odds ratio (OR) = 1.357, 95% confidence interval (CI): 1.126-1.635, p = 0.001] and Order Burkholderiales (OR = 1.336, 95% CI: 1.112-1.606, p = 0.002). In addition, 21 nominally significant causal relationships were also identified. Further, the MR-Egger intercept test and MR-PRESSO global test suggested that our MR analysis was unaffected by horizontal pleiotropy (p > 0.05). Finally, the leave-one-out analysis suggested the robustness of the results. Through the MR study, we analyzed the causal relationship of 211 GM taxa with epilepsy and determined the specific intestinal flora associated with increased epilepsy risk. Our findings may provide helpful biomarkers for disease progression and potential candidate therapeutic targets for epilepsy. In addition, in-depth analysis of large-scale microbiome GWAS datasets based on metagenomics sequencing is necessary for future studies.