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.

[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.

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.

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.

The Association of Epileptic Seizures after Acute Ischemic Stroke with Cerebral Cortical Involvement and Electroencephalographic Changes.

Background and objectives: while acute ischemic stroke is the leading cause of epilepsy in the elderly population, data about its risk factors have been conflicting. Therefore, the aim of our study is to determine the association of early and late epileptic seizures after acute ischemic stroke with cerebral cortical involvement and electroencephalographic changes. Materials and methods: a prospective cohort study in the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics Department of Neurology was conducted and enrolled 376 acute ischemic stroke patients. Data about the demographical, clinical, radiological, and encephalographic changes was gathered. Patients were followed for 1 year after stroke and assessed for late ES. Results: the incidence of ES was 4.5%, the incidence of early ES was 2.7% and the incidence of late ES was 2.4%. The occurrence of early ES increased the probability of developing late ES. There was no association between acute cerebral cortical damage and the occurrence of ES, including both early and late ES. However, interictal epileptiform discharges were associated with the occurrence of ES, including both early and late ES.

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.

Novelty preference assessed by eye tracking: A sensitive measure of impaired recognition memory in epilepsy.

OBJECTIVE: Epilepsy patients often report memory deficits despite normal objective testing, suggesting that available measures are insensitive or that non-mnemonic factors are involved. The Visual Paired Comparison Task (VPCT) assesses novelty preference, the tendency to fixate on novel images rather than previously viewed items, requiring recognition memory for the "old" images. As novelty preference is a sensitive measure of hippocampal-dependent memory function, we predicted impaired VPCT performance in epilepsy patients compared to healthy controls. METHODS: We assessed 26 healthy adult controls and 31 epilepsy patients (16 focal-onset, 13 generalized-onset, 2 unknown-onset) with the VPCT using delays of 2 or 30 s between encoding and recognition. Fifteen healthy controls and 17 epilepsy patients (10 focal-onset, 5 generalized-onset, 2 unknown-onset) completed the task at 2-, 5-, and 30-minute delays. Subjects also performed standard memory measures, including the Medical College of Georgia (MCG) Paragraph Test, California Verbal Learning Test-Second Edition (CVLT-II), and Brief Visual Memory Test-Revised (BVMT-R). RESULTS: The epilepsy group was high functioning, with greater estimated IQ (p = 0.041), greater years of education (p = 0.034), and higher BVMT-R scores (p = 0.024) compared to controls. Both the control group and epilepsy cohort, as well as focal- and generalized-onset subgroups, had intact novelty preference at the 2- and 30-second delays (p-values ≤ 0.001) and declined at 30 min (p-values > 0.05). Only the epilepsy patients had early declines at 2- and 5-minute delays (controls with intact novelty preference at p = 0.003 and p ≤ 0.001, respectively; epilepsy groups' p-values > 0.05). CONCLUSIONS: Memory for the "old" items decayed more rapidly in overall, focal-onset, and generalized-onset epilepsy groups. The VPCT detected deficits while standard memory measures were largely intact, suggesting that the VPCT may be a more sensitive measure of temporal lobe memory function than standard neuropsychological batteries.

The prevalence and correlates of PTSD, insomnia, and fatigue among people with epilepsy during Oct.7th war on Gaza: A study from Jordan.

Jordan and Palestine are tightly related countries as the same families live in the two adjacent countries. The present study sought to examine the prevalence and determinants of Post-Traumatic Stress Disorder (PTSD)symptoms, insomnia, and fatigue among a cohort of People with Epilepsy (PWE) in Jordan. This is a cross-sectional study with inclusion criteria. PTSD, insomnia, and fatigue were assessed using validated scales. Data were analyzed from 109 PWE, PTSD symptoms were screened in (35.5 %), and Insomnia was screened in 51.8 %, moreover, fatigue mean score ± SD was 44.64 ± 26.96. PTSD symptoms were significantly associated with "females" and "age above 30 years" Insomnia severity was associated with "females". Also, the regression results demonstrated that "abstinence from social media" was significantly related to lower insomnia severity. Higher fatigue severity was associated with "married" and "Generalized Tonic-Clonic Seizures", whereas, lower fatigue severity was associated with "males", and with "levetiracetam". Our findings indicate the need for actions to alleviate mental health deterioration in PWE.

Sleep profiles in epilepsy patients undergoing monotherapy and polytherapy: A comparative cross-sectional study.

OBJECTIVE: Sleep disturbances commonly reported among epilepsy patients have a reciprocal relationship with the condition; While epilepsy and anti-seizure medications (ASMs) can disrupt sleep structure, disturbed sleep can also exacerbate the frequency of seizures. This study explored subjective sleep disturbances and compared sleep profiles in patients who underwent ASM monotherapy and polytherapy. METHODS: We enrolled 176 epilepsy patients who completed a structured questionnaire containing demographic and clinical information and the Persian versions of the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Patient Health Questionnaire-9 (PHQ-9) to evaluate sleep quality, insomnia, excessive daytime sleepiness (EDS), and depressive symptoms, respectively. Chi-square and Mann-Whitney U tests were employed to analyze the association between variables, and logistic regression analysis was conducted to identify factors predicting sleep disturbances. RESULTS: Comparative analysis of mono/polytherapy groups revealed a significantly higher prevalence of insomnia and EDS among patients on polytherapy compared to monotherapy. However, no significant difference was found in sleep quality between the two groups. Logistic regression analysis revealed that a depressive mood serves as a robust predictor for sleep issues, whereas treatment type did not emerge as an independent predictor of sleep disturbances. CONCLUSION: Our findings suggest that an increased number of ASMs does not inherently result in a higher incidence of sleep issues. Therefore, multiple ASMs may be prescribed when necessary to achieve improved seizure control. Furthermore, this study underscores the importance of comprehensive management that addresses seizure control and treating affective symptoms in individuals with epilepsy.

Identifying co-morbidities and risk in people with epilepsy: The Maltese experience.

BACKGROUND: People with epilepsy are at increased risk of multiple co-morbidities that may influence risk of adverse outcomes including impact on quality of life and premature mortality. These risk factors include potentially modifiable clinical characteristics associated with sudden unexpected death in epilepsy (SUDEP). For services to tackle risk, the clinical complexity of the target epilepsy population needs to be defined. While this has been comprehensively studied in large, economically developed countries little knowledge of these issues exist in small economically developed countries, like Malta (population: 500,000). METHODS: This was a single centre study focused exclusively on patients attending Gozo General Hospital (GGH) Malta. STROBE guidance for reporting cross sectional studies was used to design and report the study. This was a retrospective review of standard care and SUDEP and seizure risks provided to all adults (over 18 years) with epilepsy attending GGH (2018-2021). RESULTS: The review identified 68 people and 92% were compliant with their anti-seizure medication. A fifth (21%) had an intellectual disability. Despite only one patient having a psychotic illness, 19% were on antipsychotic medication. Only 18% of patients had a specific epilepsy care plan, 6% nocturnal surveillance and none had received advice on SUDEP. DISCUSSION: Patient outcomes may be improved with increasing rates of personalized epilepsy care plans, appropriate nocturnal surveillance and reducing the prescription of antipsychotic medication as it is associated with greater risk of mortality. Issues such as stigma and shame appear to play a significant role in small communities and their access to care.

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.

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.

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.

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.

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.

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.

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.

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.