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.

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.

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.

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.

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.

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.

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.

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.

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.

Performance of assessment tools in predicting neural autoantibody positivity in patients with seizures.

BACKGROUND: The identification of patients with seizures of unknown etiology who would benefit from neural antibody testing necessitates effective assessment tools. The study aimed to compare the performance of the Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and the "Obvious" Indications for Neural Antibody Testing in Epilepsy or Seizures (ONES) checklist. We also intended to evaluate whether the performance of the tools varied by types of antibody. METHODS: Patients diagnosed with epilepsy, seizures, or status epilepticus of unknown etiology at West China Hospital from January 2019 to December 2021 were included. Paired serum/cerebrospinal fluid samples were analyzed for antineuronal and antiglial antibodies. The APE2 score and ONES checklist were applied, and their outcomes were compared to laboratory antibody test results. Possible false positive neuronal antibody results were excluded in sensitivity/specificity analysis reasonably. RESULTS: A total of 113 antibody-positive and 159 antibody-negative patients were enrolled in sensitivity/specificity analysis. The ONES checklist showed superior sensitivity than APE2 score (95.6 % vs.79.6 %, P < 0.001). Specificity was not statistically different (60.4 % vs. 57.9 %, P = 0.557). The negative predictive value (NPV) of ONES checklist was higher than that of APE2 score (94.8 % vs 80.7 %, P < 0.001). The positive predictive value of them was not statistically different (61.7 % vs 58.8 %, P = 0.557). APE2 score exhibited lower sensitivity for predicting LGI-Abs (52.9 % vs. 80.3 %, P = 0.022) compared to NMDAR-Abs. Similarly, ONES checklist showed lower sensitivity for LGI1-Abs than NMDAR-Abs (82.4 % vs. 100.0 %, P = 0.009). CONCLUSIONS: The ONES checklist demonstrates superior sensitivity for neural antibody positivity than APE2 score. Specificity of the two assessment tools was similar. ONES checklist performed better NPV than the APE2 score. Both assessment tools performed less well in predicting the presence of LGI1- Abs when compared to NMDAR-Abs.

Increasing incidence of Parkinson's disease in patients with epilepsy: A Nationwide cohort study.

BACKGROUND: Although epilepsy is an uncommon comorbidity of Parkinson's disease (PD), the exact incidence of PD among the patients with epilepsy is not clarified yet. OBJECTIVES: We aimed to estimate the incidence of PD in patients with epilepsy and explore the association between epilepsy and PD. METHODS: Epilepsy patients enrolled in the National Health Insurance Service Health Screening Cohort (NHIS-HealS) (2002-2013) between 2003 and 2007 were set up as the experimental group. The major outcome was the occurrence of PD. Non-epilepsy patients were obtained through Propensity Score Matching of 'greedy nearest neighbor' algorithm in 1:1 ratio. The Cox Proportional Hazards model was used to calculate PD incidence and hazard ratio (HR). RESULTS: A total of 10,510 patients were finally included in the study, which contained 5255 patients in epilepsy and non-epilepsy groups, respectively. During the follow-up period, 85 patients with Parkinson's disease among 5255 patients with epilepsy and 57 patients with Parkinson's disease among 5255 patients without epilepsy occurred. The 10,000 Person-Year (PY), representing the number of PD patients per 10,000 per year, was 21.38 in the epilepsy group and 11.18 in the non-epilepsy group. When all variables were adjusted, it was found that the epilepsy group had a 2.19 times significantly higher risk of developing Parkinson's disease than the control group (The adjusted HR: 2.19 (95% CI, 1.55-3.12)). CONCLUSION: This study indicates an increased risk of PD in patients with epilepsy. However, further research is needed to prove an exact causal relationship between these two brain disorders.

Sleep physiology in patients with epilepsy: Influence of seizures on rapid eye movement (REM) latency and REM duration.

OBJECTIVE: A well-established bidirectional relationship exists between sleep and epilepsy. Patients with epilepsy tend to have less efficient sleep and shorter rapid eye movement (REM) sleep. Seizures are far more likely to arise from sleep transitions and non-REM sleep compared to REM sleep. Delay in REM onset or reduction in REM duration may have reciprocal interactions with seizure occurrence. Greater insight into the relationship between REM sleep and seizure occurrence is essential to our understanding of circadian patterns and predictability of seizure activity. We assessed a cohort of adults undergoing evaluation of drug-resistant epilepsy to examine whether REM sleep prior to or following seizures is delayed in latency or reduced in quantity. METHODS: We used a spectrogram-guided approach to review the video-electroencephalograms of patients' epilepsy monitoring unit admissions for sleep scoring to determine sleep variables. RESULTS: In our cohort of patients, we found group- and individual-level delay of REM latency and reduced REM duration when patients experienced a seizure before the primary sleep period (PSP) of interest or during the PSP of interest. A significant increase in REM latency and decrease in REM quantity were observed on nights where a seizure occurred within 4 h of sleep onset. No change in REM variables was found when investigating seizures that occurred the day after the PSP of interest. Our study is the first to provide insight about a perisleep period, which we defined as 4-h periods before and after the PSP. SIGNIFICANCE: Our results demonstrate a significant relationship between seizures occurring prior to the PSP, during the PSP, and in the 4-h perisleep period and a delay in REM latency. These findings have implications for developing a biomarker of seizure detection as well as longer term seizure risk monitoring.

Prevalence and factors associated with psychosis among adults with epilepsy at a tertiary hospital in Uganda, cross-sectional study.

BACKGROUND: Psychotic disorders are prevalent among people with epilepsy compared to the general population. However, there is limited information regarding psychosis among people with epilepsy in Uganda. This study therefore determined the prevalence and associated factors of psychosis among adults with epilepsy attending Butabika National Referral Mental Hospital in Uganda. METHODS: This was a cross-sectional study involving adults with epilepsy. The diagnosis of psychosis was assessed using the Mini-International Neuropsychiatric Interview, module for Psychotic disorders. Logistic regression analysis identified factors associated with psychosis. RESULTS: Out of 250 participants, 6.8% had psychosis and 13.6% had depression. Psychosis was significantly associated with older age, greater perceived stigma and substance use. CONCLUSION: Psychosis affects nearly 7% of adults with epilepsy in Uganda especially among those who are older, with perceived stigma and substance use. Routine screening and early intervention to management of psychosis in PWE is highly recommended.

Can epilepsy affect normal EEG variants? A comparative study between subjects with and without epilepsy.

OBJECTIVES: To compare the prevalence of benign EEG variants (BEVs) between epileptic and non-epileptic subjects. METHODS: A prospective, observational EEG study of 1,163 consecutive patients, using the 10-20 international system with systematically two additional anterior/inferior temporal electrodes. The video-EEG monitoring duration was between 24 h and eight days. RESULTS: We identified 917 (78.9%) epileptic patients (mean age: 33.42 ± 15.5 years; females: 53.4%) and 246 (21.2%) non-epileptic patients (mean age: 35.6 ± 18.75 years; females: 54.9%). Despite a shorter mean duration of the EEG recordings, the prevalence of BEVs was higher in non-epileptic vs. epileptic patients (73.2% vs. 57.8%, p = 0.000011). This statistical difference was confirmed for lambda waves (23.6% in the non-epilepsy group vs. 14.8% in the epilepsy group, p = 0.001), POSTs (50.8% vs. 32.5%, p < 0.000001), wicket spikes (20.3% vs. 13.6%, p = 0.009) in particular in NREM and REM sleep, and 14- and 6-Hz positive bursts (13% vs. 7.1% p = 0.003). Mu rhythm was observed at the same frequency in both groups (21.1% in the non-epilepsy group vs. 22.7% in the epilepsy group). There was no difference between the two groups for rarer rhythms, such as rhythmic mid-temporal theta burst of drowsiness, small sharp spikes, and midline theta rhythm. CONCLUSIONS: There was no increase in any of the BEVs in the epilepsy group. On the contrary, BEVs were more frequent and diversified in the non-epilepsy group. Epilepsy may negatively affect the occurrence of the most common BEVs, with the exception of the mu rhythm, which is present in about one-fifth of the population with or without epilepsy.

Epilepsy and epileptiform activity in late-onset Alzheimer disease: clinical and pathophysiological advances, gaps and conundrums.

A growing body of evidence has demonstrated a link between Alzheimer disease (AD) and epilepsy. Late-onset epilepsy and epileptiform activity can precede cognitive deterioration in AD by years, and its presence has been shown to predict a faster disease course. In animal models of AD, amyloid and tau pathology are linked to cortical network hyperexcitability that precedes the first signs of memory decline. Thus, detection of epileptiform activity in AD has substantial clinical importance as a potential novel modifiable risk factor for dementia. In this Review, we summarize the epidemiological evidence for the complex bidirectional relationship between AD and epilepsy, examine the effect of epileptiform activity and seizures on cognition in people with AD, and discuss the precision medicine treatment strategies based on the latest research in human and animal models. Finally, we outline some of the unresolved questions of the field that should be addressed by rigorous research, including whether particular clinicopathological subtypes of AD have a stronger association with epilepsy, and the sequence of events between epileptiform activity and amyloid and tau pathology.

Epilepsy and demyelination: Towards a bidirectional relationship.

Demyelination stands out as a prominent feature in individuals with specific types of epilepsy. Concurrently, individuals with demyelinating diseases, such as multiple sclerosis (MS) are at a greater risk of developing epilepsy compared to non-MS individuals. These bidirectional connections raise the question of whether both pathological conditions share common pathogenic mechanisms. This review focuses on the reciprocal relationship between epilepsy and demyelination diseases. We commence with an overview of the neurological basis of epilepsy and demyelination diseases, followed by an exploration of how our comprehension of these two disorders has evolved in tandem. Additionally, we discuss the potential pathogenic mechanisms contributing to the interactive relationship between these two diseases. A more nuanced understanding of the interplay between epilepsy and demyelination diseases has the potential to unveiling the molecular intricacies of their pathological relationships, paving the way for innovative directions in future clinical management and treatment strategies for these diseases.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.