Neuroinflammation has been increasingly implicated in epileptogenesis and drug-resistant epilepsy, leading to growing research interest beyond the traditional focus on neuronal hyperexcitability. Despite the rapid expansion of research in this interdisciplinary field, a comprehensive structural mapping of its intellectual evolution and emerging frontiers is lacking. We performed a systematic bibliometric analysis of 1989 publications (2005-2026) retrieved from Web of Science Core Collection and Scopus. Analytical tools including CiteSpace, VOSviewer, and the Bibliometrix R package were employed to visualize collaboration networks, citation structures, and thematic transitions. The literature search was updated to include publications indexed up to January 4, 2026. Research output followed an exponential growth pattern (R2=0.97), peaking in 2025. China and the USA dominated the global landscape, with the Journal of Neuroinflammation and Epilepsia identified as core academic hubs. Highly cited works, led by pioneers such as Vezzani A and Aronica E, established a knowledge base centered on microglial activation and cytokine signaling. Keyword clustering identified several interconnected thematic domains. Long-standing topics included oxidative stress and hippocampal vulnerability, whereas recent citation bursts indicated increasing attention to autoimmune encephalitis, blood-brain barrier (BBB) dynamics, and the gut-brain axis. Furthermore, emerging trends highlight the ketogenic diet and network pharmacology as promising immunometabolic strategies for seizure control. This study provides the first systematic bibliometric landscape of neuroinflammation in epilepsy over the past two decades. Our findings suggest a gradual transition from studies of glial, cytokine, and vascular mechanisms toward translational interest in systemic immune-CNS interactions. These quantitative insights identify the gut-microbiota-inflammation axis and personalized immunotherapy as the next frontiers, offering a strategic roadmap for future disease-modifying interventions in refractory epilepsy.
Brain physiological pulsations drive glymphatic clearance of neurotoxins from the brain. Neurodegenerative proteinopathies, including Parkinson's disease (PD), have altered glymphatic function. This study compares brain physiological pulsations important for glymphatic clearance in PD and healthy controls (HC). PD (N = 13) and HC (N = 20) participants were evaluated using magnetic resonance encephalography (MREG), an ultrafast, 3D spherical stack-of-spirals dynamic neuroimaging technique, to assess spectral power and optical flow in cardiovascular, respiratory, and low-frequency vasomotor bands as indirect proxies for glymphatic clearance. Group differences were analyzed with two-sample t-tests, controlling for age and sex. PD participants demonstrated significantly reduced power in the cardiovascular frequency band and reduced optical flow magnitude in the low-frequency vasomotor band in regions important for visual and cognitive processing and sensorimotor function. PD is associated with alterations in physiological pulsations important for glymphatic flow. Glymphatic clearance may represent a potential therapeutic target for neurodegenerative diseases.
To evaluate clinical determinants of refractoriness and outcome in status epilepticus (SE) in a prospective low- and middle-income country (LMIC) cohort. In this single-centre prospective cohort study, 97 consecutive SE patients were classified as non-refractory status (NRSE, n = 50), refractory (RSE, n = 31), or super-refractory SE (SRSE, n = 16). A single 21 channel video-EEG was done within 24 h of presentation to the hospital. Clinical context, preexisting epilepsy history, etiology, Status Epilepticus Severity Score (STESS) and EEG findings were recorded, and outcome was assessed through in-hospital mortality. The median age of our cohort was 32 years; most common etiologies were remote symptomatic (68%), acute symptomatic (19%) and progressive symptomatic (5%). Patients with drug-sensitive epilepsy (DSE) showed low refractoriness and mortality (29%, 6%), whereas drug-resistant epilepsy and new-onset status epilepticus (NOSE) were more likely to be refractory (68% and 70% respectively) and had higher mortality (26% and 30% respectively). Overall mortality was 16.5%, increasing stepwise from 4% (NRSE) to 13% (RSE) to 63% (SRSE; p < 0.001). STESS discriminated between non-survivors and survivors (median 3 vs 0; p < 0.001). Among 85 patients with available EEG, periodic discharges (PDs) were associated with 71% mortality (p < 0.001). Status Epilepticus in the setting of DSE carries a favourable prognosis, while DRE and NOSE confer refractoriness. A short-term early EEG performed in the first 24 h is associated with refractoriness and its exact role warrants further studies.
Left anterior temporal lobe resection (TLR) in people with epilepsy is associated with a high risk of postoperative verbal memory decline. Whereas substantial evidence supports the role of preoperative verbal memory in predicting postoperative verbal memory change, the potential contribution of preoperative visual memory has been rarely investigated. We retrospectively analyzed data from 105 people with left TLR due to mesial temporal sclerosis and typical language dominance. Multiple linear and logistic regression analyses were conducted to predict the extent and risk of significant postoperative verbal memory decline based on preoperative verbal and visual memory performance, as well as clinical variables (age at surgery, age at onset, and preoperative focal to bilateral tonic-clonic seizures). In exploratory analyses, we examined the influence of dichotomized preoperative verbal and visual memory performance (impaired vs. unimpaired) on the extent and frequency of postoperative verbal memory decline, as well as the potential influence of general intellectual ability. Regression analyses showed that higher preoperative verbal memory performance was associated with more pronounced and more frequent postoperative verbal memory decline, whereas higher preoperative visual memory performance was associated with less severe and less frequent verbal memory decline. Clinical variables did not improve model prediction. Analyses with dichotomized preoperative verbal and visual memory performance confirmed the results of the regression analyses. General intellectual ability had an additional influence on postoperative verbal memory change, without changing the predictive value of preoperative verbal or visual memory performance. These findings demonstrate a cross-material relationship between preoperative visual memory and postoperative verbal memory change following left TLR. Whereas preoperative verbal memory performance likely represents functional adequacy, preoperative visual memory appears to represent functional reserve. Therefore, our findings reconcile these two concepts of postoperative verbal memory change. Additionally, the influence of general intellectual ability suggests relevance of more general cognitive reserve.
Epilepsy is a common neurological disorder in the United States that disproportionately affects African Americans. Religious and spiritual practices are important coping mechanisms that may influence health beliefs and healthcare decisions, yet their influence on epilepsy outcomes in this population remains understudied. This narrative review examines how religious and spiritual practices contribute to health decision making behaviors among African Americans living with epilepsy. A literature search was conducted using PubMed, Google Scholar, Connected Papers, and the New York University Library system, focusing on religiosity and spirituality in chronic illness, epilepsy outcomes, racial disparities, stigma in faith-based settings, and church-based health interventions. Across the reviewed literature, findings showed that religiosity and spirituality were associated with coping, finding purpose, social support, and quality of life. In epilepsy-specific studies, positive religious and spiritual coping associated with better well-being, lower anxiety and depressive symptoms, and higher quality of life, while negative religious coping was associated with poorer psychosocial outcomes. Direct evidence among African Americans with epilepsy was limited; however, available findings suggest that Black patients relied more on religion, emotional support, positive reframing, and denial as coping strategies compared to White patients. Overall, this review highlights the need to better understand how African Americans with epilepsy use religious and spiritual frameworks to manage living with a chronic neurological condition.
Functional/dissociative seizure (FDS) disorder presents diagnostic challenges due to its complex semiology and the lack of positive diagnostic biomarkers. Current evidence suggests that specific patterns of brain activity and distinct dynamics in the brain network may underlie the neurobiological mechanisms of FDS. We retrospectively analyzed ictal EEG recordings from 46 patients with FDS, in three different conditions: during resting wakefulness (RW), during resting while having eyes closed (EC), and during functional/dissociative seizures of variable semiology (FDS). The occipital EEG in the alpha band (8-13 Hz) was assessed in terms of power and functional connectivity, quantified by debiased weighted phase lag index (dwPLI). Heart rate was also analyzed across conditions. Statistical comparisons were performed via paired permutation testing with Benjamini-Hochberg correction for multiple comparisons, complemented by Bayes factors for the key FDS-EC comparisons. EEG during FDS exhibited significantly higher occipital alpha power than RW (p = 0.0003) and levels not significantly different from EC, with moderate Bayesian evidence for the absence of a difference (BF01 = 6.1). Alpha power was elevated across all FDS subtypes and was, paradoxically, numerically highest in hypermotor seizures, although subtype differences did not survive correction for multiple comparisons. Control analyses showed that the alpha power did not significantly differ across video-rated states of eyes during FDS (open, intermittently closed, closed), including when conditions were matched for eye state. Functional whole-brain connectivity in the alpha band was intermediate between the two resting conditions, being higher during FDS than during RW but lower than during EC. Heart rate was highest during FDS, with a non-significant tendency toward higher rates in hypermotor than atonic FDS. No significant correlation was found between occipital alpha power and heart rate during FDS. Our findings suggest that FDS are characterized by a paradoxical hypersynchronization in the EEG alpha band, similar to EC, despite concurrent motor activity. Increased functional alpha connectivity, simultaneous with elevated heart rate during FDS, suggests that FDSs involve altered brain network dynamics rather than simple alpha power suppression by voluntary motor activity. These findings may aid in developing positive biomarkers for FDS diagnosis.
Reliable detection of hippocampal engagement is critical in presurgical memory fMRI, yet the extent to which different paradigms differentially recruit anterior and posterior hippocampal regions at the individual level remains unclear. This study systematically compares hippocampal engagement across three commonly used memory fMRI tasks-autobiographical memory (AUT), picture encoding (PIC) and hometown walking (HTW)- at the individual level, with a particular emphasis on anterior versus posterior hippocampal regions. A total of 113 presurgical patients completed at least one memory fMRI task (AUT: n = 41; PIC: n = 53; HTW: n = 60). Hippocampal regions of interest were anatomically defined and subdivided into anterior/posterior and ipsilesional/contralesional segments. Individual-level suprathreshold activation detectability of hippocampal ROIs was assessed using standardized statistical criteria (p < 0.01, uncorrected). All tasks showed high global hippocampal detection rates. However, regional differences were observed in the anterior hippocampus, where AUT demonstrated higher detectability, particularly contralesionally (88.9 %), compared with PIC (60 %) and HTW (64.7 %) (Cramér's V = 0.259). In contrast, posterior hippocampal detection was high and comparable across tasks, with PIC showing the highest rates (80.6-97.8 %). Whole-brain analyses revealed stronger engagement of default mode network regions for AUT. Memory fMRI paradigms show distinct regional hippocampal engagement profiles and are not interchangeable for presurgical mapping at the individual level. These findings may inform task selection in presurgical memory fMRI depending on the anatomical region of interest and clinical context.
The ketogenic diet is used to treat drug-resistant epilepsy, yet the molecular mechanisms coupling metabolic state to seizure suppression remain understudied. β-Hydroxybutyrate (β-HB), a principal ketone body, exerts antiseizure effects, yet its downstream ionic mechanisms remain unclear. We used 69 C57BL/6 mice, including males and females (4-week-old for ex vivo electrophysiology and calcium imaging and 8-week-old for in vivo seizure experiments). β-HB or saline was administered after the onset of status epilepticus, induced in mice by continuous hippocampal stimulation. Intrinsic excitability and excitatory synaptic currents on hippocampal granule cells were measured using the patch clamp technique. Calcium imaging was performed after viral delivery of a genetically encoded calcium indicator into the hippocampus. In vivo, β-HB rapidly reduced the duration of status epilepticus. At the cellular level, patch-clamp recordings showed that β-HB hyperpolarized dentate granule cells (DGCs) increased action potential threshold and reduced firing frequency. Moreover, β-HB suppressed excitatory synaptic transmission onto DGCs. At the network-level, β-HB perfusion significantly decreased DGC population activity by reducing neuronal excitability and excitatory synaptic currents. Mechanistically, pharmacological blockade of G protein-gated inwardly rectifying potassium (GIRK) channels prevents the β-HB-induced suppression of DGC intrinsic excitability, excitatory synaptic transmission, and population-level activity. In contrast, inhibition of adenosine triphosphate-sensitive potassium channels had no detectable impact on β-HB-mediated modulation of DGC intrinsic excitability or network responses. These findings identify GIRK channels as a key downstream effector of β-HB signaling, providing a mechanistic link between ketogenic states and neuronal excitability, revealing a new mechanistic target for ketogenic therapies.
The incidence of sudden unexpected death in epilepsy (SUDEP) in Ireland has previously been studied. The aim of this work is to examine how frequently epilepsy related deaths, other than SUDEP, occur in the Irish population. All deaths referred to the coroner in 2019 were examined. Those with a history of possible epilepsy were noted and subjected to a more detailed assessment. Cases of SUDEP were excluded and other epilepsy related deaths were divided into those directly related to epilepsy and those indirectly related to epilepsy. We identified 54 non SUDEP epilepsy related deaths in the Republic of Ireland in 2019, 33 men and 21 women. Ages ranged from 22 to 92 years with a median age of 58 years. Twenty-two deaths were directly related to epilepsy with 32 indirectly related. This is the first study of non SUDEP epilepsy related deaths in Ireland. It is important that these deaths, which like SUDEP may be potentially preventable, are recognised that and that risk reduction strategies are put in place. While this work demonstrates that the interrogation of coronial records is a useful way to monitor epilepsy mortality, efforts should be made to ensure more accurate certification of these deaths.
To examine the relationship between epilepsy diagnosis behavior and perceptions of stigma among children with epilepsy and their parents. This study is descriptive, cross-sectional, and correlational. The sample of the study conducted in Türkiye consisted of children with epilepsy and their parents aged 9-16 years (n = 94). Data were collected face-to-face using the "Child and Parent Information Form", the "Epilepsy Disclosure Scale - Child and Parent Version (EDS)", and the "Stigma Scale Perceived by Children with Epilepsy and Their Parents (SSP)". The mean age of the children participating in the study was 11.79 ± 1.85 years, and 57.4% were male. The mean total score on the EDS for children was 6.26 ± 3.30, and the mean SSP score was 1.98 ± 0.91; for parents, the scores were 6.49 ± 3.59 and 2.54 ± 0.99, respectively. In children, the type of epilepsy significantly affected SSP scores (p = 0.008), receiving psychological support significantly affected SSP scores (p = 0.034), and family history of epilepsy significantly affected EDS scores (p = 0.020). In parents, age (p = 0.006) and education level (p = 0.001) significantly affected EDS scores, and age also affected SSP scores (p = 0.047). A significant positive correlation was found between SSP and EDS behavior in both children (r = 0.643) and parents (r = 0.503); p < 0.001). In hierarchical regression analyses, perceived stigma remained a significant independent predictor of children's EDS scores after controlling for family history of epilepsy, psychological support, and type of epilepsy (β = 0.448; ΔR2 = 0.135; p = 0.006), whereas in the parent model, its effect became marginal (β = 0.255; p = 0.059) when age and education level were controlled, with education level emerging as the strongest predictor (β = 0.425; p = 0.008). Parents reported significantly higher SSP compared with their children (t = -4.936; p < 0.001), but no significant difference was observed for EDS (p = 0.667). Significant positive associations were also found between children's and parents' SSP (r = 0.673; p < 0.001) and EDS (r = 0.423; p = 0.003). Perceived stigma in children with epilepsy and their parents significantly predicts concealment behavior, and both stigma perception and concealment behavior are shared family experiences. It is recommended that family-based psychosocial counseling and training interventions be planned in nursing care to address stigma coping strategies.
Acute symptomatic seizures (ASyS) are clinical seizures occurring at the time of a systemic insult or in close temporal association with a documented brain injury. We aimed to determine the 3-year mortality following a first ASyS. We previously conducted a prospective, population-based cohort comprising all individuals with a first seizure during 2017 from a defined geographic area. Individuals with ASyS were identified from this cohort using ILAE criteria and stratified by provoking factor. Mortality was assessed at 30 days, 1 year, and 3 years following the event, and age-standardized mortality ratios (SMRs) were calculated at 1 and 3 years using age-matched and sex-matched national mortality data. Among 207 cases of first ASyS, identified from a population of 542,868, there were 61 deaths (29.5%) during 3 years of follow-up. Mortality at 30 days, 1 year, and 3 years was 12.6%, 22.2%, and 29.5%, respectively. The SMR was 19.7 (95% CI 14.4-26.3) at 1 year and 10.4 (95% CI 7.9-13.4) at 3 years. Mean age at first ASyS was 52.1 years and at death 70.5 years. Excluding the substance use group, 3-year mortality rose to 45.5% (50/110). Pneumonia was the most frequent cause of death (17/61, 27.9%). ASyS is a common presentation and is associated with markedly increased mortality over 3 years. These findings underscore the prognostic importance of ASyS as a clinical indicator of increased long-term mortality, particularly in medically complex patients.
This Phase I study evaluated the safety, tolerability, and pharmacokinetics of a 30-min topiramate injection (intravenous [IV] TPM) infusion compared with oral topiramate (oral TPM) in healthy adult participants. In this randomized, open-label, dose escalation, crossover study with 37 healthy participants received single doses of 50, 100, or 200 mg of an oral TPM tablet and an IV TPM formulation, using sulfobutylether beta-cyclodextrin as a solubilizer and stabilizer, infused over 30 min, with a 12-day washout. Blood samples for pharmacokinetic assessments were collected at predose through 192 h post dose. Concentration-time data were analyzed using non-compartmental analysis, and IV TPM relative bioavailability was determined. Topiramate injection AUCinf (total exposure) increased linearly with dose. The mean (90% confidence interval [CI]) relative bioavailability was 97.1% (94.6-99.7%). The mean (± SD) clearance for 50, 100, and 200 mg IV TPM was 1.4 L/h (±0.2), 1.3 L/h (±0.2), and 1.3 L/h (±0.2), respectively. Half-life was comparable across routes. Dose proportionality was demonstrated for AUCinf over the 50-200 mg range. No serious adverse events were reported. These findings suggest that when oral TPM administration is not feasible, equivalent doses of topiramate injection infused over 30 min at intervals can temporarily replace oral dosing until it can be resumed.
Lennox-Gastaut syndrome (LGS) is a rare developmental and epileptic encephalopathy associated with treatment-resistant seizures, profound neurodevelopmental impairments, and high caregiver burden. While seizure control is often prioritized in clinical trials, caregivers emphasize the importance of assessing behavior, communication, and quality of life. This study explored the perspectives of caregivers, clinicians, and advocates on existing instruments for measuring these domains in individuals with LGS. We conducted four focus groups with caregivers (n = 22), epilepsy advocates (n = 5), and clinicians (n = 6). Participants reviewed pre-selected instruments for each domain before the sessions. Questions elicited feedback on instruments assessing the three domains, as well as other relevant domains for LGS. Discussions were recorded, transcribed, and thematically analyzed. Five themes emerged: (1) Behavior instruments - the Aberrant Behavior Checklist was favored for relevance and ease, while the Adaptive Behavior Assessment System-3 and Vineland Adaptive Behavior Scales-3 were viewed as lengthy or developmentally mismatched; (2) Communication instruments - the Communication Matrix was preferred for capturing nonverbal and alternative communication, while the Communication and Symbolic Behavior Scales lacked relevance; (3) Quality of life instruments - no clear preference emerged between Quality of Life Inventory-Disability and CDKL5 Deficiency Disorder Severity Assessment; (4) Impact on caregivers - negative language, time burden, and administration logistics posed challenges; and (5) Unaddressed gaps - sleep, gastrointestinal health, caregiver burden, socialization, and safety were noted as insufficiently captured. Participants identified strengths and limitations of existing instruments and highlighted several unmet measurement needs. These insights underscore the need for relevant, inclusive tools that are aligned with the lived experiences of individuals with LGS and their families.
Flickering visual stimulation can evoke neural oscillations, which can influence ongoing brain activity. Electrophysiological recordings of neural oscillations in the ripple band (80-180 Hz) show that these high-frequency oscillations occur in the neocortex and the hippocampus, that they phase-synchronize across long distances, and that ripple oscillations in the neocortex often precede those in the hippocampus during wakefulness. It is therefore possible that the neocortical ripple oscillations propagate beyond sensory areas to the hippocampus, inducing ripple oscillations. To test the hypothesis that neocortical ripple oscillations induced by visual stimulation induce hippocampal ripple oscillations, we conduct an exploratory experiment (N = 8) in humans, using ultra-high frequency visual stimulation to induce ripple oscillations recorded through electrodes implanted in or near the hippocampus. Although hippocampal ripple oscillations, so-called sharp-wave-ripples, mostly occur during quiet rest or slow-wave sleep, we aim to increase their abundance using visual stimulation during wakefulness in this exploratory study. We hypothesize that ultra-high frequency visual stimulation increases the number of sharp-wave-ripples relative to an eyes-open resting-state baseline. In this exploratory and preliminary study, we observe significantly more sharp-wave-ripples per second during periods of stimulation compared to a resting-state baseline before and after the stimulation. The increased number of sharp-wave ripples during stimulation suggests that ultra-high-frequency visual stimulation can be used as a safe noninvasive tool to influence sharp-wave ripples, which offers the potential to improve memory. This exploratory study examines a noninvasive way to influence brain activity linked to memory. Sharp-wave ripples (SWRs) in the hippocampus are important for forming and recalling memories, but they are reduced in aging and Alzheimer’s Disease. The experiment tests whether very fast flickering light, called ultra-high frequency visual stimulation (UHV-stimulation), can increase the number of SWRs. Eight epilepsy patients with implanted electrodes receive UHV-stimulation while their brain activity is recorded. The results suggest that UHV-stimulation increases the number of SWRs compared to a resting baseline. Other properties of SWRs do not change, and participants report no negative effects. These preliminary results suggest that UHV-stimulation might support memory in the future.
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Epidemiology, pathophysiology, clinical characteristics, established clinical- and experimental treatment options are discussed with regard to the lifespan. Attention is dedicated to special features of older patients. This narrative review was conducted in line with a structured literature search performed in the PubMed/MEDLINE database to identify relevant publications on post-traumatic epilepsy. Search terms included Medical Subject Headings (MeSH) and free-text keywords related to traumatic brain injury, post-traumatic seizures, epileptogenesis, epidemiology, and treatment. No restrictions on publication date were applied in order to include both seminal and contemporary studies. The literature was narratively synthesized to provide a concise and clinically relevant overview of post-traumatic epilepsy. Posttraumatic epilepsies of adults are frequently occurring in older patients. Little available data concerning age characteristics like TBI etiologies and PTE considerations by age groups with related management approaches exists. This review provides a condensed overview shedding also light on biological and clinical interlinks. TBI requires individual risk assessment for posttraumatic epilepsy and other neurological and psychiatric sequelae in the long-term course contributing to a "traumatic brain injury disease syndrome". Innovative approaches regarding diagnostics and approaches for interventions are discussed.
To explore how caregivers perceived their child's participation in four randomized controlled trials (RCTs) for Dravet syndrome (DS), conducted between 1996 and 2024, on stiripentol (STP), cannabidiol (CBD), fenfluramine (FFA), and soticlestat (TAK-935). A semi-structured, cross-sectional survey, in French, assessed families' motivations for enrolling in the trials, their perceptions throughout the different trial phases, and challenges encountered. Ten caregivers reported that their child had participated in the STP trial, 20 in the CBD trial, 13 in the FFA trial, and 1 in the TAK-935 trial. In most cases (39/44, 88%), trial participation was proposed by the treating (paediatric) neurologist. The main reasons for non-enrolment were satisfactory seizure control, the trial having ended before awareness, and ineligibility. Motivations for participation were mostly access to new treatments, hope, and confidence in the medical team, whereas non-participation was primarily driven by concerns about adverse events, emotional impact of uncertainty, and potential placebo assignment. Overall, trial experiences were rated positively: hope, fear of not completing the trial, and stress were the most frequently reported emotions throughout the trial, while the primary barriers related to daily schedules to accommodate regular medical appointments. Regret and solitude post-trial were scored very low. To our knowledge, this is the first survey exploring the caregivers' perceptions of participation in epilepsy clinical trials. Patient and stakeholder engagement is essential for optimizing trial recruitment, acceptance and understanding of the failures.
Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis presents relapse risk and potential functional impairment, with no established maintenance treatment guidelines. The study aimed to uncover prognostic signatures, and identify predictors of relapse and poor outcome using real-world evidence. This multicenter retrospective study included anti-LGI1 encephalitis patients from five tertiary hospitals in Eastern China between January 2015 and January 2024, with ≥ 24-month follow-up. Relapse was defined as the presence of new or worsening clinical features after at least 3 months of stability or improvement. Poor outcome was defined as a modified Rankin Scale score > 2 at last follow-up. A total of 104 patients were included (median age 56.5 years, 60.6% male). Following the acute phase, the majority (66.3%) received prolonged corticosteroid treatment (≥6 months) without steroid-sparing maintenance immunotherapy (SSMI), whereas 16.3% received SSMI. Twelve patients (11.5%) experienced relapse. Hyponatremia at diagnosis was more common in relapsing patients (p = 0.017), and was significantly associated with an increased risk of relapse in Cox regression (hazard ratio = 4.67, 95% confidence interval [CI] = 1.41-15.53, p = 0.012). Poor outcome was observed in 17 patients (16.3%), with male sex (odds ratio [OR] = 5.12, 95% CI = 1.27-34.48, p = 0.041) and hyponatremia (OR = 4.69, 95% CI = 1.54-15.47, p = 0.008) as potential risk factors. This study suggests that hyponatremia is associated with an increased risk of relapse and poor outcome in anti-LGI1 encephalitis. These findings may facilitate individualized risk stratification, but further validation in larger prospective cohorts is needed. Anti-LGI1 encephalitis is an autoimmune brain disorder characterized by cognitive impairment, seizures, and psychiatric symptoms. While immunotherapy improves outcomes, relapses occur and long-term functional recovery varies. Risk factors for relapse and poor outcome remain inadequately defined. This multicenter study included 104 patients with minimum 24-month follow-up. Relapse occurred in 11.5% and poor functional outcome in 16.3%. Hyponatremia at diagnosis was significantly associated with a higher risk of relapse and poor outcome. These findings suggest hyponatremia may be a potential biomarker for risk stratification, thereby guiding individualized therapeutic strategies. However, further research is needed to confirm these observations.
Falls are common in individuals with dementia and pose a significant problem in acute hospital care. Aging and dementia affect functional brain networks including the default mode network (DMN), dorsal attention network (DAN) and salience network (SAN). The DAN and SAN are essential for the rapid detection of responses to unexpected stimuli. We hypothesize that global efficiency within these networks is reduced in patients with dementia who experience falls compared with those who do not. We analyzed 347 inpatients with dementia from a neurological clinic in Vienna, Austria. Of 153 available EEGs, only those with normal findings were included. FC was calculated using the phase-locking-value across delts, theta, alpha, and beta bands. The characteristic path length of the DAN, SAN and DMN was computed. Fallers showed reduced global efficiency in the DAN. FC between the right rostral middle frontal gyrus and left middle frontal gyrus was decreased in delta, theta, and alpha bands - regions involved in visual stimulus processing and executive control. Reduced DAN connectivity may impair the ability to respond to unexpected stimuli, increasing fall risk in individuals with dementia. This supports the role of attention network dysfunction in motoric cognitive risk syndrome. Falls are a significant problem in dementia, not well understood so far. Identifying network level dysfunction in dementia related falls offers a novel biomarker for risk stratification and possible targets for future interventions.
The association between autism spectrum disorder (hereafter referred to as autism) and tuberous sclerosis complex (TSC) is well established, yet the developmental pathways linking genetic mutation, cortical pathology, and epilepsy with autism remain unclear. The Tuberous Sclerosis 2000 Study recruited children newly diagnosed with TSC (N = 125). Data on mutation status, cortical tuber burden (magnetic resonance imaging/computed tomography), seizure history, and cognitive ability were collected. Approximately 10 years later, follow-up assessments of autism, cognitive ability, and epilepsy were completed (n = 86). Almost 40% of participants met diagnostic criteria for autism, with an additional 42% showing elevated autistic traits. Structural equation modeling identified two indirect pathways linking TSC1/TSC2 mutation with the autism factor score: one via higher cortical tuber burden and infantile spasms and one via spasms alone. Concurrent seizure severity and lower intelligence quotient scores were also associated with higher autism factor scores. These findings provide preliminary longitudinal evidence supporting developmental associations between genetic vulnerability, cortical pathology, and early severe epilepsy with later autism. This highlights the importance of further investigation of early epileptic activity and associated neurodevelopmental outcomes in TSC and may inform understanding of epilepsy-related pathways associated with autism.