Reproductive and fetal outcomes in women with epilepsy: a systematic review and meta-analysis.

OBJECTIVE: Although early evidence shows that epilepsy can increase the risks of adverse pregnancy, some outcomes are still debatable. We performed a systematic review and meta-analysis to explore the effects of maternal and fetal adverse outcomes in pregnant women with epilepsy. METHODS: PubMed, Embase, Cochrane, and Web of Science were employed to collect studies that investigated the potential risk of obstetric complications during the antenatal, intrapartum, or postnatal period, as well as any neonatal complications. The search was conducted from inception to November 16, 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included original studies. The odds ratio (OR) values were extracted after adjusting for confounders to measure the relationship between pregnant women with epilepsy and adverse maternal or fetal outcomes. The protocol for this systematic review is registered with PROSPERO ID CRD42023391539. RESULTS: Of 35 articles identified, there were 142,577 mothers with epilepsy and 34,381,373 mothers without epilepsy. Our study revealed a significant association between pregnant women with epilepsy (PWWE) and the incidence of cesarean section, preeclampsia/eclampsia, gestational hypertension, induction of labor, gestational diabetes and postpartum hemorrhage compared with those without epilepsy. Regarding newborns outcomes, PWWE versus those without epilepsy had increased odds of preterm birth, small for gestational age, low birth weight (<2500 g), and congenital malformations, fetal distress. The odds of operative vaginal delivery, newborn mortality, and Apgar (≤ 7) were similar between PWWE and healthy women. CONCLUSION: Pregnant women affected by epilepsy encounter a higher risk of adverse obstetric outcomes and fetal complications. Therefore, it is crucial to develop appropriate prevention and intervention strategies prior to or during pregnancy to minimize the negative impacts of epilepsy on maternal and fetal health.

Prevalence of abnormal electrocardiographic findings and associated factors among patients with epilepsy at Jimma Medical Center, Ethiopia; Hospital-based cross-sectional study.

BACKGROUND: A person with epilepsy experiences recurrent seizures as a result of a persistent underlying disorder. About 50 million people globally are impacted by it, with 4 million of those being in Sub-Saharan Africa. One of the most frequent comorbidities that raise the mortality and morbidity rates of epileptic patients is abnormal Electrocardiographic (ECG) findings. Thus, the purpose of this study is to evaluate the prevalence of abnormal ECG findings in epileptic patients that might lead to increased risk of sudden cardiac death. METHODOLOGY: A hospital based cross-sectional study was at Jimma Medical Center of Ethiopia on epileptic patients who were on follow-up at neurologic clinics during the data collection period. The malignant ECG characteristics and was identified using the ECG abnormality tool. To facilitate analysis, the gathered data was imported into Epidata version 3.1 and exported to the SPSS version 26. The factors of abnormal ECG and sudden death risk were examined using bivariate logistic regression. RESULTS: The study comprised 190 epileptic patients, with a mean age of 32 years. There were more men than women, making up 60.2%. A 43.2% (n = 80) frequency of ECG abnormalities was identified. According to the study, early repolarization abnormalities were the most common ECG abnormalities and increased with male sex and the length of time a person had seizures (AOR) of 4.751 and 95% CI (.273,.933), p = 0.029, compared to their female counterparts. CONCLUSION: The frequency of malignant ECG alterations in epileptic patients on follow-up at Jimma Medical Center in Ethiopia is described in the study. According to the study, there were significant ECG alterations in epileptic individuals. Male gender and longer duration of epilepsy raise the risk of abnormal ECG findings that could result in sudden cardiac death.

[Risk of epilepsy after a first epileptic seizure with unknown etiology in elderly patients]. / Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.

AIM: 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. MATERIALS AND METHODS: 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. 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. CONCLUSION: 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.

TITLE: Riesgo de epilepsia tras una primera crisis epiléptica de etiología desconocida en pacientes de edad avanzada.Objetivo. Los pacientes que comienzan con crisis de origen desconocido en la edad avanzada no están bien estudiados. El objetivo es caracterizar clínicamente a estos pacientes y predecir el riesgo de desarrollar epilepsia a largo plazo. Materiales y métodos. Es un estudio observacional retrospectivo en pacientes mayores de 55 años con una primera crisis epiléptica de causa desconocida. Se recogieron los datos desde la historia clínica, incluyendo electroencefalograma (EEG) y resonancia magnética (RM) cerebral. Resultados. Se incluyó a 87 pacientes (58,6% varones; 71,5 ± 8,1 años). El seguimiento medio fue de 7,3 ± 4,9 años. El factor de riesgo vascular más frecuente fue la hipertensión arterial (77%; n = 67). Las crisis focales con alteración de la conciencia fueron el tipo de crisis más frecuente (44,8%; n = 39), seguidas de las crisis focales con evolución a bilaterales tonicoclónicas (39,1%; n = 34). La RM cerebral mostró atrofia cortical (50%; n = 42) y signos de enfermedad vascular de pequeño vaso (EVPV) (67,8%; n = 57). Se observaron anomalías epileptiformes intercríticas en el EEG en un 43,7% (n = 38) de los pacientes, mayoritariamente con localización temporal (94,7%; n = 36). Hasta un 44,8% (n = 39) presentaba deterioro cognitivo leve basalmente. La recurrencia de crisis, observada en 49 pacientes (56,1%), sucedió con una mediana de 12 meses (rango intercuartílico: 4,4-25,9). Finalmente, 71 pacientes (81,6%) desarrollaron epilepsia. Conclusión. El riesgo de epilepsia a largo plazo tras una crisis única de etiología desconocida en pacientes de edad avanzada es superior al 80%. La hipertensión arterial y el deterioro cognitivo leve en el inicio son las características clínicas más frecuentes. En la RM, la atrofia cortical y la presencia de EVPV son frecuentes, y los EEG de rutina no suelen mostrar alteraciones epileptiformes.

Challenging behaviour and epilepsy in patients with intellectual disability: frequency and mutual association.

Comorbid epilepsy and challenging behaviours is quiet common in patients with ID (intellectual disability). This study aims to determine the frequency and mutual association between epilepsy and challenging behaviours. In this cross-sectional analytical study, 252 patients were enrolled through convenient sampling technique. Comorbid epilepsy and CB (challenging behaviour) were seen in 111 (44.6%) and 116 (46.6%) patients, respectively. Epilepsy and severity of intellectual disability (ID) are statistically and significantly associated with challenging behaviour. This study concluded that comorbid epilepsy is more common among people with ID as compared to the general population. The clinical variables, i.e. comorbid epilepsy and severity of ID have statistically significant association with the CB.

Dynamical modulation of hypersynchronous seizure onset with transcranial magneto-acoustic stimulation in a hippocampal computational model.

Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.

Postictal psychiatric symptoms: A neurophysiological study.

OBJECTIVE: Postictal psychiatric symptoms (PPS) are a relatively common but understudied phenomenon in epilepsy. The mechanisms by which seizures contribute to worsening in psychiatric symptoms are unclear. We aimed to identify PPS prospectively during and after admission to the epilepsy monitoring unit (EMU) in order to characterize the postictal physiologic changes leading to PPS. METHODS: We prospectively enrolled patients admitted to the EMU and administered repeat psychometric questionnaires during and after their hospital stay in order to assess for postictal exacerbations in four symptom complexes: anger/hostility, anxiety, depression, and paranoia. Electroclinical and electrographic seizures were identified from the EEG recordings, and seizure durations were measured. The severity of postictal slowing was calculated as the proportion of postictal theta/delta activity in the postictal EEG relative to the preictal EEG using the Hilbert transform. RESULTS: Among 33 participants, 8 demonstrated significant increases in at least one of the four symptoms (the PPS+ group) within three days following the first seizure. The most common PPS was anger/hostility, experienced by 7/8 participants with PPS. Among the 8 PPS+ participants, four experienced more than one PPS. As compared to those without PPS (the PPS- group), the PPS+ group demonstrated a greater degree of postictal EEG slowing at 10 min (p = 0.022) and 20 min (p = 0.05) following seizure termination. They also experienced significantly more seizures during the study period (p = 0.005). There was no difference in seizure duration between groups. SIGNIFICANCE: Postictal psychiatric symptoms including anger/hostility, anxiety, depression, and paranoia may be more common than recognized. In particular, postictal increases in anger and irritability may be particularly common. We provide physiological evidence of a biological mechanism as well as a demonstration of the use of quantitative electroencephalography toward a better understanding of postictal neurophysiology.

Relationships among anxiety, depression, and health-related quality of life in adult epilepsy: A network analysis.

OBJECTIVE: Comorbid depression and anxiety in patients with epilepsy (PWE) are common and frequently under-treated, thus, causing poor health-related quality of life (HRQoL). However, little is known regarding the interconnections between anxious/depressive symptoms and the dimensions of HRQoL. Therefore, we conducted a network analysis to explore these relationships in detail among Chinese adult PWE. METHODS: A cohort of adult PWE was consecutively recruited from the First Affiliated Hospital of Chongqing Medical University. HRQoL, depression, and anxiety were measured with Quality of Life in Epilepsy Inventory-31, Neurological Disorders Depression Inventory for Epilepsy, and Generalized Anxiety Disorder 7-Item Scale, respectively. A regularized partial correlation network was constructed to investigate the interconnections between symptoms of anxiety/depression and the dimensions of HRQoL. We calculated expected influence (EI) and bridge expected influence (BEI) values to identify the most influential nodes. RESULTS: A total of 396 PWE were enrolled in this study, 78.1% of whom had focal onset epilepsy. The prevalence of anxiety and depression was 30.3% and 28.8%, respectively. The symptoms "frustrated" and "uncontrollable worry" had the highest EI values, whereas "emotional well-being", "seizure worry", "difficulty finding pleasure", and "nervousness or anxiety" had the highest BEI values. CONCLUSION: This study provides new insights into the relationships among anxiety, depression, and HRQoL. Critical central symptoms and bridge symptoms identified in the network might help to quickly identify PWE comorbid anxiety and depression in busy outpatient settings, thereby enabling early intervention and enhancing quality of life.

Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.

BACKGROUND: Brain tumors are one of the leading causes of epilepsy, and brain tumor-related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi-omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi-omics technology-based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. METHODS: First, we provided a general review of epilepsy, BTRE, and multi-omics techniques. Next, we described the specific multi-omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. RESULTS: Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma-related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR-128 and miRNA-196b participate in BTRE development. miR-128 might be negatively associated with the possibility of tumor-related epilepsy development. The lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non-epileptic gliomas. In another proteomics study, a high expression of AQP-4 was detected in the brain of GBM patients with seizures. By using quantitative RT-PCR and immunohistochemistry assay, a study revealed that patients with astrocytomas and oligoastrocytomas showed high BCL2A1 expression and poor seizure control. By performing immunohistochemistry, several studies have reported the relationship between D2HG overproduction and seizure occurrence. Ki-67 overexpression in WHO grade II gliomas was found to be associated with poor postoperative seizure control. According to metabolomics research, the PI3K/AKT/mTOR pathway is associated with the development of glioma-related epileptogenesis. Another metabolomics study found that SV2A, P-gb, and CAD65/67 have the potential to function as biomarkers for BTRE. CONCLUSIONS: Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE.

Diagnosing epileptic seizures in patients with Alzheimer's disease and deciding on the appropriate treatment plan.

INTRODUCTION: Alzheimer's disease (AD) is the predominant cause of dementia and a significant contributor to morbidity among the elderly. Patients diagnosed with AD face an increased risk of epileptic seizures. AREAS COVERED: Herein, the authors review the challenges in the diagnosis of seizures in patients with AD, the risks of seizures related to medications used in AD and the pharmacological treatment of seizures in AD. The authors also provide the reader with their expert opinion on the subject matter and future perspectives. EXPERT OPINION: Healthcare professionals should maintain a vigilant approach to suspecting seizures in AD patients. Acute symptomatic seizures triggered by metabolic disturbances, infections, toxins, or drug-related factors often have a low risk of recurrence. In such cases, addressing the underlying cause may suffice without initiating antiseizure medications (ASMs). However, unprovoked seizures in certain AD patients carry a higher risk of recurrence over time, warranting the use of ASMs. Although data is limited, both lamotrigine and levetiracetam appear to be reasonable choices for controlling seizures in elderly AD patients. Decisions should be informed by the best available evidence, the treating physician's clinical experience, and the patient's preferences.

Applying Proteomics and Computational Approaches to Identify Novel Targets in Blast-Associated Post-Traumatic Epilepsy.

Traumatic brain injury (TBI) can lead to post-traumatic epilepsy (PTE). Blast TBI (bTBI) found in Veterans presents with several complications, including cognitive and behavioral disturbances and PTE; however, the underlying mechanisms that drive the long-term sequelae are not well understood. Using an unbiased proteomics approach in a mouse model of repeated bTBI (rbTBI), this study addresses this gap in the knowledge. After rbTBI, mice were monitored using continuous, uninterrupted video-EEG for up to four months. Following this period, we collected cortex and hippocampus tissues from three groups of mice: those with post-traumatic epilepsy (PTE+), those without epilepsy (PTE-), and the control group (sham). Hundreds of differentially expressed proteins were identified in the cortex and hippocampus of PTE+ and PTE- relative to sham. Focusing on protein pathways unique to PTE+, pathways related to mitochondrial function, post-translational modifications, and transport were disrupted. Computational metabolic modeling using dysregulated protein expression predicted mitochondrial proton pump dysregulation, suggesting electron transport chain dysregulation in the epileptic tissue relative to PTE-. Finally, data mining enabled the identification of several novel and previously validated TBI and epilepsy biomarkers in our data set, many of which were found to already be targeted by drugs in various phases of clinical testing. These findings highlight novel proteins and protein pathways that may drive the chronic PTE sequelae following rbTBI.

The incidence and risk factors of secondary epilepsy after viral encephalitis in children: A 10-year single-center retrospective analysis.

Secondary epilepsy is a common concomitant disease of viral encephalitis (VE) in children. However, the risk factors for secondary epilepsy after VE remain debated. The aim of this study was to perform a 10-year single-center retrospective analysis to investigate the incidence and risk factors of secondary epilepsy after VE in children. A total of 8691 patients suffered from VE in our hospital between December 2011 and February 2022 were included. The patients were divided into control group (Group C) and epilepsy group (Group E) according to whether they followed secondary epilepsy. Information about treatment process was collected from medical records to determine the incidence. Univariate analysis and multivariate logistic regression analysis were performed to identify the independent risk factors. In the current study, the occurrence of secondary epilepsy after VE in pediatric patients was 10.99% (385 of 3503). The results of univariate and multivariate analysis showed that unconsciousness, convulsions, times of epilepsy >2, epileptiform discharge of Electroencephalogram (EEG), and cortical and subcortical damage of magnetic resonance imaging/computer tomography were the significant risk factors for secondary epilepsy after VE. Nearly one tenth of pediatric patients suffered from secondary epilepsy after VE. Interventions for identified risk factors should be used to prevent the occurrence of secondary epilepsy.

Factors associated with sleep disturbances in children and adolescents with Angelman Syndrome.

BACKGROUND: Angelman Syndrome (AS) is a rare genetic disorder characterised by hyperactivity, overexcitability, developmental delays, and lack of speech. METHODS: This study used secondary data analysis to investigate sleep disturbances in children and adolescents (n = 212) who are enrolled in the Global Angelman Syndrome Registry. Participants were divided into two groups based on the presence or absence of sleep disturbance. The cut-off score of 40 on the Sleep Disturbance Scale for Children was used to indicate the presence or absence of sleep disturbances. Sleep disturbances and their association with co-occurring conditions were examined regarding challenging behaviour, language and communication, infancy history, gastrointestinal symptoms, and epilepsy. Multiple regression was then conducted to investigate possible predictors for sleep disturbances. RESULTS: Children and adolescents with AS, with and without sleep disturbances, differed considerably regarding anxiety. Sleep disturbances were significantly associated with an ability to use spoken words and computerised communication devices, and anxiety was a predictor of sleep disturbances. CONCLUSION: Future research is necessary to replicate this novel research, and to advance the clinical treatment of sleep disturbances in children and adolescents with AS.

Postsurgical Outcomes of Mesial Temporal Lobe Epilepsy due to Hippocampal Sclerosis Associated with Calcified Neurocysticercosis.

The aim of this study was to analyze postsurgical outcomes for individuals with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) who underwent anterior temporal lobectomy, based on the presence of calcified neurocysticercosis (cNCC). A retrospective cross-sectional study was conducted on 89 patients with MTLE-HS who underwent anterior temporal lobectomy between January 2012 and December 2020 at a basic epilepsy surgery center located in Lima, Peru. We collected sociodemographic, clinical, and diagnostic information. The postsurgical results were analyzed using bivariate analysis according to the Engel classification. We included 89 individuals with a median age of 28 years (interquartile range [IQR]: 24-37), and more than half (55.1%) were male. Seventeen (19.1%) were diagnosed with cNCC. A greater number of patients with cNCC had lived in rural areas of Peru during their early life compared with those without cNCC (12 [70.6%] versus 26 [36.1%]; P = 0.010). Patients with cNCC exhibited a greater median frequency of focal to bilateral tonic-clonic seizures per month (1 [IQR: 0-2] versus 0 [0-0.5]; P = 0.009). Conversely, a lower proportion of patients with cNCC reported a history of an initial precipitating injury in comparison to the group without cNCC (4 [23.5%] versus 42 [58.3%]; P = 0.014). At the 1-year follow-up, most patients (82.4%) with cNCC were categorized as Engel IA. Similarly, at the 2-year follow-up, nine (75.0%) were classified as Engel IA. Our findings suggest that most patients diagnosed with cNCC exhibit favorable postsurgical outcomes, comparable to those without cNCC. Additionally, it can be postulated that cNCC may play a role as an initial precipitating injury.

Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis.

OBJECTIVE: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. METHOD: We conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson's chi-square or Fisher's exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. RESULTS: We selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations. Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8--34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6- 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2--35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2--24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1--90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2--24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. CONCLUSIONS: In our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.

Bidirectional relationship between late-onset epilepsy (LOE) and dementia: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD). METHODS: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests. RESULTS: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication. CONCLUSION: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study.

Genetic determinants of global developmental delay and intellectual disability in Ukrainian children.

BACKGROUND: Global developmental delay or intellectual disability usually accompanies various genetic disorders as a part of the syndrome, which may include seizures, autism spectrum disorder and multiple congenital abnormalities. Next-generation sequencing (NGS) techniques have improved the identification of pathogenic variants and genes related to developmental delay. This study aimed to evaluate the yield of whole exome sequencing (WES) and neurodevelopmental disorder gene panel sequencing in a pediatric cohort from Ukraine. Additionally, the study computationally predicted the effect of variants of uncertain significance (VUS) based on recently published genetic data from the country's healthy population. METHODS: The study retrospectively analyzed WES or gene panel sequencing findings of 417 children with global developmental delay, intellectual disability, and/or other symptoms. Variants of uncertain significance were annotated using CADD-Phred and SIFT prediction scores, and their frequency in the healthy population of Ukraine was estimated. RESULTS: A definitive molecular diagnosis was established in 66 (15.8%) of the individuals. WES diagnosed 22 out of 37 cases (59.4%), while the neurodevelopmental gene panel identified 44 definitive diagnoses among the 380 tested patients (12.1%). Non-diagnostic findings (VUS and carrier) were reported in 350 (83.2%) individuals. The most frequently diagnosed conditions were developmental and epileptic encephalopathies associated with severe epilepsy and GDD/ID (associated genes ARX, CDKL5, STXBP1, KCNQ2, SCN2A, KCNT1, KCNA2). Additionally, we annotated 221 VUS classified as potentially damaging, AD or X-linked, potentially increasing the diagnostic yield by 30%, but 18 of these variants were present in the healthy population of Ukraine. CONCLUSIONS: This is the first comprehensive study on genetic causes of GDD/ID conducted in Ukraine. This study provides the first comprehensive investigation of the genetic causes of GDD/ID in Ukraine. It presents a substantial dataset of diagnosed genetic conditions associated with GDD/ID. The results support the utilization of NGS gene panels and WES as first-line diagnostic tools for GDD/ID cases, particularly in resource-limited settings. A comprehensive approach to resolving VUS, including computational effect prediction, population frequency analysis, and phenotype assessment, can aid in further reclassification of deleterious VUS and guide further testing in families.

Predictive Model for Estimating the Risk of Epilepsy After Aneurysmal Subarachnoid Hemorrhage: The RISE Score.

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021). We collected demographic data, clinical and radiologic variables, data on early-onset seizures (EOSs), and data on development of epilepsy. Exclusion criteria were previous structural brain lesion, epilepsy, and ≤7 days' follow-up. Multiple Cox regression was used to evaluate factors independently associated with unprovoked remote seizures (i.e., epilepsy). The best fitting regression model was used to develop a predictive score. Performance was evaluated in an external validation cohort of 308 patients using receiver-operating characteristic curve analysis. RESULTS: From an initial database of 743 patients, 419 met the inclusion criteria and were included in the analysis. The mean age was 60 ± 14 years, 269 patients (64%) were women, and 50 (11.9%) developed epilepsy within a median follow-up of 4.2 years. Premorbid modified Rankin Score (mRS) (hazard ratio [HR] 4.74 [1.8-12.4], p = 0.001), VASOGRADE score (HR 2.45 [1.4-4.2], p = 0.001), surgical treatment (HR 2.77 [1.6-4.9], p = 0.001), and presence of EOSs (HR 1.84 [1.0-3.4], p = 0.05) were independently associated with epilepsy. The proposed scale, designated RISE, scores 1 point for premorbid mRS ≥ 2 (R), VASOGRADE-Yellow (I, Ischemia), surgical intervention (S), and history of EOSs (E) and 2 points for VASOGRADE-Red. RISE stratifies patients into 3 groups: low (0-1), moderate (2-3), and high (4-5) risk (2.9%, 20.8%, and 75.7% developed epilepsy, respectively). On validation in a cohort from a different tertiary care center (N = 308), the new scale yielded a similar risk distribution and good predictive power for epilepsy within 5 years after aSAH (area under the curve [AUC] 0.82; 95% CI 0.74-0.90). DISCUSSION: The RISE scale is a robust predictor of post-SAH epilepsy with immediate clinical applicability. In addition to facilitating personalized diagnosis and treatment, RISE may be of value for exploring future antiepileptogenesis strategies.

Anxiety, depression, sleep disorders and quality of life in parents of children with first unprovoked seizure and epilepsy.

BACKGROUND: Parents of a child with neurological problems such as seizures and epilepsy experience significant mental distress. Little is known about the mental state of parents in such a stressful situation. This study aims to determine the prevalence of self-reported depression, anxiety, sleep disorders, and quality of life in parents of children with epilepsy and first unprovoked seizure. METHODS: This cross-sectional study was conducted among the parents of children diagnosed with first unprovoked seizure and epilepsy admitted to the Pediatric Neurology Department, Outpatient Unit of Inönü University Medical Faculty Hospital. Participants filled out a questionnaire investigating demographic variables, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Pittsburgh Sleep Quality Index (PSQI), and 36- Item Short-Form Health Survey (SF-36). RESULTS: 113 parents participated in the study. Depression was found in 7%, anxiety in 14%, and sleep quality disorder in 33.3% of parents of children diagnosed with epilepsy on the basis of moderate or higher severity, while depression was found in 8.9%, anxiety in 14.3%, and sleep disorder in 21.4% of parents of children diagnosed with first unprovoked seizure. There was no statistically significant difference between the groups. Mothers were at higher risk for loss of physical function and social functionality. There was a positive correlation between BAI, BDI, and PSQI scores. Quality of life sub-dimension measured by SF-36 was associated with different levels of depression, anxiety, and sleep quality. CONCLUSION: Addressing parental psychiatric problems by professionals involved in the treatment of children with a history of seizures may have the potential to provide further support for the family and the care of patients.

Predictors of medical intractability in children with epilepsy onset during the first two years of life, excluding infantile epileptic spasm syndrome.

PURPOSE: Early childhood epilepsy presents a significant challenge, with approximately 30 % of individuals experiencing treatment failure. This study aimed to identify predictors of medical intractability in children with epilepsy onset during the first two years of life, excluding infantile epileptic spasm syndrome. METHODS: A total of 323 children were retrospectively evaluated. The analyses included a review of medical records for demographic, laboratory, radiological, and electroencephalographic (EEG) findings. Children were diagnosed with drug-resistant epilepsy (DRE) according to the ILAE diagnostic criteria. Twenty-one potential prognostic predictors were examined in relation to medical intractability. RESULTS: Among the 323 children (56.7 % male), 119 (36.8 %) had unknown epilepsy, 131 (40.6 %) had structural epilepsy, 53 (16.4 %) had genetic epilepsy, and 20 (6.2 %) had metabolic epilepsy. Over a median follow-up of 68 months, 55.4 % of the children achieved ≥6 months of seizure freedom, 33.1 % developed DRE, and the remaining 11.5 % had rare ongoing seizures but did not meet the criteria for DRE because they were only treated with one antiseizure medication at the last follow-up. Univariate logistic regression analyses identified ten risk factors significantly associated with DRE. Multivariate logistic regression analyses revealed that the presence of developmental delay at epilepsy onset (p = 0.000; OR 7.890; 95 %CI 2.713 to 22.945), history of status epilepticus (p = 0.000; OR 8.247; 95 %CI 3.619 to 18.793), number of antiseizure medications (ASMs) at the sixth month of diagnosis (p = 0.000; OR 20.585; 95 %CI 8.993 to 47.117), and initial EEG findings (p = 0.046; OR 2.366; 95 %CI 1.015 to 5.518) were predictors of medical intractability. Nineteen (5.9 %) children died during follow-up for various reasons, including progressive neurogenetic or neurodegenerative disorders. CONCLUSION: Developmental delay at epilepsy onset, a history of status epilepticus, the use of two or more ASMs in the sixth month of diagnosis, and abnormal initial EEG findings were associated with medical intractability.

EEG microstates in epilepsy with and without cognitive dysfunction: Alteration in intrinsic brain activity.

OBJECTIVE: This study aims to investigate the difference between epilepsy comorbid with and without cognitive dysfunction. METHOD: Participants were classified into patients with epilepsy comorbid cognitive dysfunction (PCCD) and patients with epilepsy without comorbid cognitive dysfunction (nPCCD). Microstate analysis was applied based on 20-channel electroencephalography (EEG) to detect the dynamic changes in the whole brain. The coverage, occurrence per second, duration, and transition probability were calculated. RESULT: The occurrence per second and the coverage of microstate B in the PCCD group were higher than that of the nPCCD group. Coverage in microstate D was lower in the PCCD group than in the nPCCD group. In addition, the PCCD group has a higher probability of A to B and B to A transitions and a lower probability of A to D and D to A transitions. CONCLUSION: Our research scrutinizes the disparities observed within EEG microstates among epilepsy patients both with and without comorbid cognitive dysfunction. SIGNIFICANCE: EEG microstate analysis offers a novel metric for assessing neuropsychiatric disorders and supplies evidence for investigating the mechanisms and the dynamic change of epilepsy comorbid cognitive dysfunction.