Widespread slow oscillations support interictal epileptiform discharge networks in focal epilepsy.

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation. Here, the amplitude and phase synchronization of SOs preceding propagating and non-propagating IEDs were compared in 22 patients with focal epilepsy undergoing intracranial electroencephalography (EEG) evaluation. Intracranial channels were categorized into the irritative zone (IZ) and normal zone (NOZ) regarding the presence of IEDs. During wakefulness, we found that pre-IED SOs within the IZ exhibited higher amplitudes for propagating IEDs than non-propagating IEDs (delta band: p = 0.001, theta band: p < 0.001). This increase in SOs was also concurrently observed in the NOZ (delta band: p = 0.04). Similarly, the inter-channel phase synchronization of SOs prior to propagating IEDs was higher than those preceding non-propagating IEDs in the IZ (delta band: p = 0.04). Through sliding window analysis, we observed that SOs preceding propagating IEDs progressively increased in amplitude and phase synchronization, while those preceding non-propagating IEDs remained relatively stable. Significant differences in amplitude occurred approximately 1150 ms before IEDs. During non-rapid eye movement (NREM) sleep, SOs on scalp recordings also showed higher amplitudes before intracranial propagating IEDs than before non-propagating IEDs (delta band: p = 0.006). Furthermore, the analysis of IED density around sleep SOs revealed that only high-amplitude sleep SOs demonstrated correlation with IED propagation. Overall, our study highlights that transient but widely distributed SOs are associated with IED propagation as well as generation in focal epilepsy during sleep and wakefulness, providing new insight into the EEG substrate supporting IED networks.

A region-specific modulation of sleep slow waves on interictal epilepsy markers in focal epilepsy.

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.

Ictal EEG desynchronization during low-voltage fast activity for prediction of surgical outcomes in focal epilepsy.

OBJECTIVE: The authors investigated alterations in functional connectivity (FC) and EEG power during ictal onset patterns of low-voltage fast activity (LVFA) in drug-resistant focal epilepsy. They hypothesized that such changes would be useful to classify epilepsy surgical outcomes. METHODS: In a cohort of 79 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation as well as resective surgery, FC changes during the peri-LVFA period were measured using nonlinear regression (h2) and power spectral properties within/between three regions: the seizure onset zone (SOZ), early propagation zone (PZ), and noninvolved zone (NIZ). Desynchronization and power desynchronization h2 indices were calculated to assess the degree of EEG desynchronization during LVFA. Multivariate logistic regression was employed to control for confounding factors. Finally, receiver operating characteristic curves were generated to evaluate the performance of desynchronization indices in predicting surgical outcome. RESULTS: Fifty-three patients showed ictal LVFA and distinct zones of the SOZ, PZ, and NIZ. Among them, 39 patients (73.6%) achieved seizure freedom by the final follow-up. EEG desynchronization, measured by h2 analysis, was found in the seizure-free group during LVFA: FC decreased within the SOZ and between regions compared with the pre-LVFA and post-LVFA periods. In contrast, the non-seizure-free group showed no prominent EEG desynchronization. The h2 desynchronization index, but not the power desynchronization index, enabled classification of seizure-free versus non-seizure-free patients after resective surgery. CONCLUSIONS: EEG desynchronization during the peri-LVFA period, measured by within-zone and between-zone h2 analysis, may be helpful for identifying patients with favorable postsurgical outcomes and also may potentially improve epileptogenic zone identification in the future.

COVID-19 vaccination hesitancy and safety among adult people with epilepsy in eastern China.

OBJECTIVE: This study assesses the hesitancy and safety of vaccination administration for the novel 2019 Coronavirus Disease (COVID-19) among adult people with epilepsy (PWE). METHODS: We recruited adult PWE who visited the outpatient epilepsy clinic from August 2021 to February 2022. We administered a structured questionnaire and a face-to-face interview regarding demographic factors, epilepsy characteristics, and relevant vaccine issues to all patients. Factors related to receiving a vaccine and epilepsy-related events after vaccination were then analyzed. RESULTS: A total of 501 PWE were surveyed; 288 were unvaccinated and 213 were vaccinated. Patients without jobs (OR: 0.59; 95% CI: 0.37-0.95, p = 0.03) were less likely to receive the vaccine compared to students or those with jobs. Other factors associated with vaccination were a higher number of anti-seizure medications (OR: 0.72; 95% CI: 0.55-0.95, p = 0.02) and a lower pre-vaccine seizure frequency (OR: 2.21; 95% CI: 1.06-4.59, p = 0.03). Of the 213 vaccinated patients, 10 (4.70%) reported at least one local and/or systemic side effect. Most patients (92.50%) did not report worse seizures within one month of vaccination. Poor ASM adherence (OR: 15.06; 95% CI: 1.75-129.87, p = 0.01) and fatigue/stimulant drinks such as caffeine (OR: 50.59; 95% CI: 7.57-337.94, p < 0.01) were significantly associated with seizure worsening within one month of receiving the COVID-19 vaccination. CONCLUSION: Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. There was a low risk of seizure worsening in the short term after vaccination in PWE.

Effects of anti-seizure therapies on sleep in patients with epilepsy: A literature review.

Sleep disorder is common in epilepsy. With a recent rapid development in sleep medicine, it has been increasingly recognized that anti-seizure therapies, either anti-seizure medications (ASMs) or non-pharmaceutical approaches, can take direct or indirect influence on sleep in patients with epilepsy. Here, we systematically review the effect of anti-seizure treatments on sleep. ASMs targeting at different sites exerted various effects on both sleep structure and sleep quality. Non-pharmaceutical treatments including resective surgery, ketogenic diet, and transcranial magnetic stimulation appear to have a positive effect on sleep, while vagus nerve stimulation, deep brain stimulation, and brain-responsive neurostimulation are likely to interrupt sleep and exacerbate sleep-disordered breathing. The potential mechanisms underlying how non-pharmacological approaches affect sleep are also discussed. The limitation of most studies is that they were largely based on small cohorts by short-term observations. Further well-designed and large-scale investigations in this field are warranted. Understanding the effect of anti-seizure therapies on sleep can guide clinicians to optimize epilepsy treatment in the future.

Molecular interaction of stress granules with Tau and autophagy in Alzheimer's disease.

Stress Granules (SGs) are RNA granules composed of untranslated mRNA and associated proteins, which are related to the cytoplasmic metabolism of mRNA in response to cellular stress and certain drug stimuli. Physiological SGs are dynamic structures that protect cells from the effects of stress, and continuous stress ripens the SGs into more stable complexes. Numerous studies have found that dysregulation of RNA metabolism in stress response led to misfolded protein aggregation in the pathophysiology of neurodegenerative diseases. For example, in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and Parkinson's disease (PD), SGs aggregation is mainly due to up-regulation of SGs formation and down-regulation of SGs clearance. Recent studies have revealed the role of SGs in the pathogenesis and pathology of AD, especially the interaction of SGs and RNA-binding proteins with Tau and autophagy. Aggregation of SGs and increased RNA-binding proteins, especially TIA1, can facilitate Tau misfolding and propagation, and vice versa. Autophagy dysfunction disrupts the normal pathway of SGs clearance. In this review, we summarized the regulation of SGs and their relationship with Tau protein and autophagy, as well as the pathological mechanisms of AD such as RNA splicing, microglial cell proliferation and phagocytosis.

Hippocampal Malrotation Could Be Less Significant in Epilepsy Caused by Focal Cortical Dysplasia Type I and Type II.

OBJECTIVES: Debates over the relationship between hippocampal malrotation (HIMAL) and epilepsy continue without consensus. This study explores the role of HIMAL in a cohort of epilepsy caused by focal cortical dysplasia (FCD). METHODS: In this study, 90 patients with epilepsy caused by FCD type I and type II and 48 healthy adults underwent a 3 Tesla MRI following a dedicated epilepsy protocol for the analysis of the prevalence and morphologic features of HIMAL. In addition, numerous clinical characteristics and hippocampal volumes were evaluated. RESULTS: The cohort included a total of 90 patients (32 were HIMAL, 58 were non-HIMAL). Among these patients, 32 (35.6%) had HIMAL (22 left, four right, and six bilateral), which did not differ from the 48 controls, where 16 (33.3%) had HIMAL (12 left, two right, and two bilateral). Neither the quantitative features of HIMAL (diameter ratio, dominant inferior temporal sulcus height ratio, medial distance ratio, dominant inferior temporal sulcus angle, and parahippocampal angle), nor the accompanying characteristics of HIMAL (vertical dominant inferior temporal sulcus, enlarged temporal horn, and a low position of ipsilateral fornix) showed differences between patients with FCD and controls. No statistical difference in the clinical characteristics between FCD patients with HIMAL and those without was found. Neither the side nor the existence of HIMAL was correlated with the lateralization and location of FCD. As to the hippocampal volume, there was no difference between FCD patients with HIMAL and those without. CONCLUSION: Hippocampal malrotation is a common morphologic variant in healthy controls as well as in patients with epilepsy caused by FCD type I and type II. Hippocampal malrotation could be less significant in epilepsy caused by FCD type I and type II.

Application of Cerebrospinal Fluid AT(N) Framework on the Diagnosis of AD and Related Cognitive Disorders in Chinese Han Population.

BACKGROUND: Studies concerning the impact of the AT(N) framework on diagnostic capability in the dementia population are lacking. We aimed to explore the diagnostic application of CSF AT(N) framework in clinical routines of Alzheimer's disease (AD) as well as differential diagnosis of other cognitive diseases in the Chinese Han population. PATIENTS AND METHODS: A total of 137 patients with cognitive disorders received CSF tests of Aß42, t-tau and p-tau181. Their CSF biomarker results were categorized and interpreted by the AT(N) framework. Neurologists provided a diagnosis both pre- and post-CSF biomarker disclosure with corresponding diagnostic confidence. RESULTS: The total initial diagnosis included 79 patients with AD and 58 patients with non-AD (NAD). The results of CSF biomarkers led to a diagnostic change of 28% in the cohort. Approximately 81.5% (n=53) of 65 patients whose CSF biomarker showed an underlying AD pathology were finally diagnosed as AD, with an increase of 17.5% in diagnostic confidence. Thirty-seven CSF results indicating NAD pathologic changes contributed to an exclusion of AD in 56.8% (n=21) of the patients along with a modest increase of 9.8% in average confidence. Thirty-five patients with normal CSF biomarkers maintained the diagnosis of NAD in 68.6% (n=24) of the group, leading to a slight elevation of 7.6% in confidence. CONCLUSION: We found that the presence of amyloid pathology (A+) is contributable to diagnosing AD and improving confidence. On occasion of negative amyloid pathology (A-), with or without tau pathology, gaining uncertainty of the primary AD diagnosis would diminish the corresponding confidence. To the best of our knowledge, this is the first study performed in the Chinese Han population with cognitive disorders that explores the clinical capability of CSF AT(N) framework in a quantitative way.

The Mechanistic Role of Bridging Integrator 1 (BIN1) in Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of dementia. The majority of AD cases are late-onset, multifactorial cases. Genome-wide association studies have identified more than 30 loci associated with sporadic AD (SAD), one of which is Bridging integrator 1 (BIN1). For the past few years, there has been a consensus that BIN1 is second only to APOE as the strongest genetic risk factor for SAD. Therefore, many researchers have put great effort into studying the mechanism by which BIN1 might be involved in the pathogenetic process of AD. To date, plenty of evidence has shown that BIN1 may participate in several pathways in AD, including tau and amyloid pathology. In addition, BIN1 has been indicated to take part in other relevant pathways such as inflammation, apoptosis, and calcium homeostasis. In this review, we systemically summarize the research progress on how BIN1 participates in the development of AD, with the expectation of providing promising perspectives for future research.

The discriminative capacity of CSF ß-amyloid 42 and Tau in neurodegenerative diseases in the Chinese population.

INTRODUCTION: In the past few years, the ß-amyloid 42 peptide and tau protein in cerebrospinal fluid (CSF) have become primary diagnostic biomarkers in differentiating Alzheimer's disease (AD) and cognitive normal controls. As we know, several neurodegenerative diseases have been reported to overlap with AD in neuropathology and clinical symptoms. To examine the discriminative utility of these biomarkers in AD and other neurodegenerative diseases, we measured them in a cohort of Chinese population. METHODS: We measured CSF Aß42, t-tau and p-tau181 by ELISA tests and calculated the ratios of t-tau/Aß42 and p-tau181/Aß42 in 240 Chinese Han patients with AD (n = 82), frontotemporal dementia (FTD, n = 20), Huntington's disease (HD, n = 27), multiple system atrophy (MSA, n = 24), spinocerebellar ataxia type-3 (SCA3, n = 27), amyotrophic lateral sclerosis (ALS, n = 36) and controls (n = 24). RESULTS: As expected, all biomarkers showed high discriminative capacity between AD and non-AD groups (p < .05) except for the elevated CSF t-tau in FTD (p > .05). Comparing with the controls, tau related biomarkers significantly elevated in the FTD (p < .001) and MSA (p < .05) groups. Surprisingly, comparing with controls, we found that CSF Aß42 increased remarkably in the SCA3 (p < .05), HD and ALS groups (p < .001), achieving a high specificity, respectively. CONCLUSION: To our best knowledge, this is the first comprehensive study in the Han Chinese population that confirmed the discriminative utility of CSF Aß42 and tau biomarkers between AD and other neurodegenerative diseases.

Fulminant bilateral acute retinal necrosis complicated with secondary herpes simplex type-1 viral encephalitis: A case report.

RATIONALE: Acute retinal necrosis (ARN), which is characterized by peripheral necrotizing retinitis, severe retinal arteritis, and progressive inflammatory reaction in the vitreous and anterior chambers, has been reported in cases with herpes simplex encephalitis (HSE). It is a relatively rare complication secondary to HSE. However, cases presented with viral encephalitis following ARN were seldom reported. PATIENT CONCERNS: A 43-year-old immunocompetent male patient manifested the aforesaid reverse situation. He developed HSE following 3-day systemic steroid therapy for abrupt ocular pain and rapidly decreased visual acuity, which was later diagnosed as ARN. Polymerase chain reaction (PCR) analysis of vitreous specimen verified herpes simplex virus-1 (HSV-1) infection. DIAGNOSIS: HSE associated with ARN. INTERVENTIONS: The patient was treated with intravenous acyclovir (500 mg every 8 h) for 21 days. A pulse of intravenous methylprednisolone, 500 mg/d for 5 days was given as an anti-inflammatory therapy, followed by prednisone taper. OUTCOMES: The patient's neurological symptoms got improved very soon after the therapy, but his vision acuity remained no perception of light in both eyes. LESSONS: The present case indicates that ARN can also be a risk factor for HSE. Once ARN was suspected, corticosteroid should be applied with caution and in combination with antiviral treatment to avoid progressive duplication of virus and its spread to the brain.

Cerebral sparganosis presenting with atypical postcontrast magnetic resonance imaging findings: a case report and literature review.

BACKGROUND: Sparganosis, a rare and severe parasitic infection caused by the larvae of Spirometra species or simply sparganum, generally involves subcutaneous tissue or muscle. But occasionally, sparganum can also invade the human brain, resulting in cerebral sparganosis. CASE PRESENTATION: A 33-year-old woman presented with a 10-day history of headache. Postcontrast magnetic resonance imaging (MRI) revealed an irregular lesion with enhancement and the tunnel-shaped focus extending to the contralateral hemiphere. Cerebrospinal fluid (CSF) analysis disclosed pleocytosis (166 cells/µL) and an elevated protein concentration (0.742 g/L). Enzyme-linked immunosorbent assay (ELISA) revealed positive sparganum-specific antibody in both blood and CSF. Finally, the diagnosis of cerebral sparganosis was comfirmed. She received praziquantel treatment and got a favorable outcome during six-month follow-up. CONCLUSIONS: Irregular enhancement and the tunnel sign that extends to the contralateral hemisphere on postconstrast MRI are unusual presentations of cerebral sparganosis. ELISA for sparganum-specific antibody can help confirm the diagnosis. Although surgery is the preferred treatment for cerebral sparganosis, praziquantel might also achieve satisfying outcomes.

Mutation screening in Chinese patients with familial Alzheimer's disease by whole-exome sequencing.

Familial Alzheimer's disease (FAD) is characterized by a positive family history of dementia and typically occurs at an early age with an autosomal dominant pattern of inheritance. Amyloid precursor protein (APP), presenilin1 (PSEN1), and presenilin2 (PSEN2) are the major causative genes of FAD. The spectrum of mutations in patients with FAD has been investigated extensively in the Caucasian population but rarely in the Chinese population. Here, we performed whole-exome sequencing in a total of 15 unrelated Chinese patients with FAD. Among them, 12 were found to carry missense variants in APP, PSEN1, and PSEN2. Two novel variants (APP: p.D244G, p.K687Q), 3 variants not previously associated with FAD (APP: p.T297M, p.D332G; PSEN1: p.R157S), and 7 previously reported pathogenic variants (APP: p.V717I; PSEN1: p.M139I, p.T147I, p.L173W, p.F177S, p.R269H; PSEN2: p.V139M) were identified. The novel variant APP p.K687Q was classified as likely pathogenic, and the other 4 variants (APP: p.D244G, p.T297M, p.D332G; PSEN1: p.R157S) were classified as uncertain significance. Therefore, APP, PSEN1, and PSEN2 mutations account for 2 (25.0%), 5 (62.5%), and 1 (12.5%) of the genotyped cases positive for mutations, respectively. Furthermore, the genotype-phenotype correlations were described. Our findings broaden the genetic spectrum of FAD with APP, PSEN1, and PSEN2 variants.