Journals
2026 EN
Rodrigues Thiago Pereira · Bocca Leonardo Favi · Yacubian Elza Marcia Targas
+7 more
Abstract Objective To identify long‐term predictors of seizure outcome after anterior temporal lobectomy (ATL) in a large, homogeneous cohort of patients with drug‐resistant temporal lobe epilepsy (TLE) and MRI‐defined unilateral hippocampal sclerosis (HS), all operated on by a single neurosurgeon with extended follow‐up. Methods We retrospectively analyzed 281 consecutive patients with unilateral HS who underwent standardized ATL performed by the same senior neurosurgeon. All patients had at least two years of follow‐up (mean 10.8 ± 5.79 years). Clinical history, neuropsychological evaluation, long‐term video‐EEG monitoring, and 1.5T MRI constituted the preoperative dataset. Twenty‐one variables were assessed as potential predictors of seizure outcome. Kaplan–Meier survival curves and univariate log‐rank tests identified candidate predictors; variables with p < .10 were entered into a multivariate Cox regression model. Cognitive and quality‐of‐life outcomes were evaluated using standardized neuropsychological batteries and the ESI‐55 questionnaire. Results At 10 years postoperatively, 62.6% of patients remained seizure‐free (Engel I). Univariate analysis identified seven factors associated with seizure freedom, including history of focal‐to‐bilateral tonic–clonic seizures, history of status epilepticus, presence of psychogenic non‐epileptic seizures, IED predominance or exclusivity in the operated lobe, ictal onset exclusively in the operated lobe, and a preoperative neuropsychological deficit confined to the operated temporal lobe. Multivariate analysis revealed three independent predictors of seizure outcome: history of status epilepticus (HR = 2.11; p = .002), ictal onset confined to the operated temporal lobe (HR = .57; p = .018), and preoperative neuropsychological deficit restricted to the operated temporal lobe (HR = .59; p = .040). Cognitive outcomes were generally stable; left ATL was associated with greater verbal memory decline. Quality‐of‐life improved significantly at 2‐year follow‐up ( p < .001), with better outcomes among seizure‐free patients. Significance In this large single‐surgeon cohort with one of the longest follow‐up durations reported, most patients with unilateral HS achieved durable seizure freedom after ATL. Status epilepticus, consistent ictal localization to the operated temporal lobe, and concordant preoperative neuropsychological deficit emerged as robust long‐term predictors. These findings reinforce the value of detailed presurgical evaluation—particularly ictal EEG concordance and neuropsychological lateralization—in optimizing surgical counseling, risk stratification, and patient selection.
Journals
2026 EN
Dell'Isola Giovanni B. · Muda Alice · Giordano Lucio
+10 more
Abstract The SCN1A gene is implicated in a broad spectrum of epilepsy phenotypes, ranging from self‐limited genetic epilepsy with febrile seizures plus (GEFS+) to severe developmental and epileptic encephalopathies such as Dravet syndrome (DS). While fenfluramine (FFA) has demonstrated strong efficacy in DS, its role in SCN1A ‐related epilepsies beyond DS has not been thoroughly investigated. We conducted a multicenter observational study including 11 patients with SCN1A ‐related GEFS+ who received FFA as adjunctive therapy. All patients had previously failed to achieve adequate seizure control with valproate and, in most cases, additional antiseizure medications. FFA was introduced following the DS titration protocol, with a mean dose of 0.39 mg/kg/day. FFA addition led to a mean seizure frequency reduction of 91%, with more than half of the patients achieving complete seizure freedom. Reduced EEG abnormalities were documented in 5/11 patients of the cohort, including complete normalization in 3/11 patients. Furthermore, subjective caregiver reports indicated perceived improvements in patients' alertness and behavioral responses. FFA was well tolerated, with only mild and transient adverse events reported. These findings support the potential role of FFA as an effective and well‐tolerated treatment option in patients with SCN1A ‐related GEFS+. Plain Language Summary GEFS+ is a genetic epilepsy frequently caused by changes in the SCN1A gene. In a multicenter real‐world study of 11 people with SCN1A‐related GEFS+, adding fenfluramine to usual care substantially reduced seizures, with several becoming seizure‐free. EEG recordings improved, and caregivers reported better alertness in some patients. Treatment was generally well tolerated, with only mild, temporary side effects.
Journals
2026 EN
Cortesi Paolo A. · Fornari Carla · Boncristiano Alessandra
+13 more
Abstract Objective Dravet syndrome (DS) is a rare disease with a high clinical and socioeconomic impact on patients, society, and the healthcare system. The recent approval of therapies such as fenfluramine (FFA) has transformed the treatment landscape; however, data on their cost‐effectiveness are still scarce. This study evaluates the real‐world cost‐effectiveness of adding FFA to existing therapies for DS patients from the Italian National Healthcare System perspective. Methods This retrospective multicenter observational study included 124 Italian DS patients initiating FFA as add‐on treatment between February 2017 and August 2022 and followed until December 2022 or disenrollment (post‐FFA period). Data on drug treatments, healthcare resource utilization, and main outcomes—rescue medication, hospital admission, and status epilepticus (SE) episodes—were collected both in the post‐FFA period and in a pre‐FFA period matching each patient's follow‐up duration (median 2.9 years). Annual per‐patient rates and costs, with 95% confidence intervals (CI), were determined for each outcome in both periods. Incremental cost‐effectiveness ratios (ICERs) with 95% CIs and cost‐effectiveness acceptability curves (CEACs) were also calculated. Results The median age at FFA initiation was 8.5 years. Mean annual healthcare cost of patients with DS was €5740 (95% CI 2896–9930) in the pre‐FFA period. FFA introduction added an annual per‐patient drug acquisition cost of €16 476, but it significantly reduced frequency and costs associated with hospital admissions and acute events. ICERs were €2187 per rescue medication avoided, €12 935 per hospital admission avoided, and €17 301 per SE episode avoided. Significance This real‐world study demonstrates that despite increased drug acquisition costs, FFA provides clinical and economic benefits by reducing acute events and related healthcare costs. The investment required to reduce acute events is justifiable given the young age of DS patients and its impact on the healthcare system, families, and caregivers. Future research should incorporate indirect costs and a broader societal perspective. Plain Language Summary Dravet syndrome is a severe and rare type of epilepsy that can be very hard on patients and their families. It also puts a great burden on healthcare systems. A new treatment, fenfluramine (FFA), helps better control seizures. Although FFA increases drug treatment costs, this cost is actually balanced out by reduced emergency visits and hospital stays for severe seizures, leading to overall lower healthcare expenses.
Journals
2026 EN
Perulli Marco · De Gioia Alessia · Ruggiero Federica
+10 more
Abstract Objective CDKL5 deficiency disorder (CDD) is an early‐onset developmental and epileptic encephalopathy characterized by frequent drug‐resistant seizures, cerebral visual impairment, motor dysfunction, and sleep and gastrointestinal disturbances. Preliminary evidence suggests that highly purified cannabidiol (CBD) may reduce seizure frequency, but data on its effects on comorbidities are lacking. This study aimed to evaluate the efficacy and safety of CBD in individuals with CDD. Methods We conducted a prospective, open‐label, single‐center study including patients with CDD aged >1 year. Outcomes included motor seizure frequency, caregiver‐ and clinician‐rated Clinical Global Impression (CGI), and changes in sleep, motor abilities, and EEG at 3, 6, and 12 months. CBD plasma levels were measured with High‐Performance Liquid chromatography–Mass Spectrometry (HPLC‐MS). Results Eight of nine patients (all females; median age 10 years, range 1–24) completed the study, with a retention rate at 12 months of 8/9 (89%). One discontinued at 6 months due to a skin rash. A > 50% seizure reduction was observed in 8/9 patients at 3 months, 6/9 at 6 months, and 1/8 at 12 months. Seven patients showed some degree of vigilance improvements, three in motor performance, and two in sleep and constipation. All caregivers reported at least minimal overall improvement (CGI score 3) at 3 months, and three reported marked improvement (CGI score 2), with a peak at 3 months. Five patients showed adverse events during the trial, but none were considered serious. The median CBD dose at all time‐points was 15.6 mg/kg/day (IQR 10.0–18.9) corresponding to a plasma dose of 69.9 ng/mL (IQR 29.8–114.6) and the median concentration/dose ratio was 4.7 (IQR 2.7–6.8). Significance The safety and efficacy of highly purified CBD in CDD were consistent with previous reports in the literature, with possible benefits beyond seizure control. Further studies are warranted to assess non‐seizure outcomes and compare long‐term efficacy across treatment options. Plain Language Summary We studied nine girls with CDKL5 deficiency disorder who had frequent, hard‐to‐treat seizures. They received cannabidiol for up to 1 year, added to their usual medicines. Most children had fewer seizures in the first months of treatment. Some families also noticed better alertness, eye contact, movement, sleep, or constipation. Side effects were usually mild and manageable. Although seizure frequency often returned to baseline by the end of the study, most families chose to continue cannabidiol. Because this was a small study without a placebo group, these results are preliminary, and larger controlled trials are needed.
Journals
2026 EN
Muhammad Anees · Nosrati Mohammad Sadegh Shams · Dostmohammadi Alireza
+8 more
Abstract The FBXW7 gene encodes a substrate‐recognition component of the Skp1‐Cul1‐F‐box (SCF) E3 ubiquitin ligase complex, which targets key regulatory proteins for proteasomal degradation. Recently, loss‐of‐function FBXW7 variants have been associated with a novel neurodevelopmental disorder characterized by heterogeneous clinical features. Most reported pathogenic variants cluster within the WD40 domains, while variants in other regions, such as the F‐box domain, remain poorly characterized. In this study, we performed trio‐exome sequencing on a 3‐year‐old girl with Early‐Onset Childhood Absence Epilepsy. We analyzed the identified FBXW7 variant using multiple in silico tools for pathogenicity prediction and structural modeling. Clinical phenotype was compared with previously reported cases. We identified a novel de novo missense variant in FBXW7 , c.926G>C; p.(Arg309Pro), affecting a highly conserved residue in the F‐box domain. Notably, unlike prior cases predominantly associated with WD40 domain variants and severe phenotypes, our patient exhibited a much milder clinical presentation consisting of isolated, drug‐responsive absence seizures without intellectual disability. Structural modeling predicted significant impairment in protein–protein binding affinity, particularly with the SCF complex component SKP1, supporting a potentially disruptive effect of the p.(Arg309Pro) substitution on complex assembly. Overall, our findings expand the genotypic and phenotypic spectrum of FBXW7‐related disorders. Variants in the F‐box domain may result in milder neurological phenotypes compared to those in the WD40 domains, suggesting domain‐specific effects and potentially distinct pathogenic mechanisms. Plain Language Summary The FBXW7 gene helps regulate the stability of many proteins essential for brain development and function. Changes in this gene have recently been linked to neurodevelopmental disorders with epilepsy. We identified a new FBXW7 variant in a 3‐year‐old girl with early‐onset absence epilepsy. Computer‐based modeling suggests that this change weakens the protein's normal interactions. Our findings broaden the spectrum of FBXW7 ‐related disorders and indicate that variants in different gene regions may result in variable clinical severity.
Journals
2026 EN
Grubor Irena · Serednicka Kristina · Säll Cornelia
+3 more
Abstract Objective To investigate a recently developed MRI technique for mapping the Mean Diffusivity of Tissue (MDT), which improves diffusion MRI imaging of the cerebral cortex by reducing partial volume effects from cerebrospinal fluid (CSF). As cortical lesions are common in patients with focal epilepsy, we explored the clinical value of MDT imaging in patients with drug resistant epilepsy and low‐grade glioma. Method This is a prospective study in which 18 patients undergoing evaluation for epilepsy surgery and five patients undergoing evaluation for low‐grade glioma were recruited. Patients underwent conventional MRI and MDT imaging. The images were analyzed by a neuroradiologist who visually assessed the images using a lesion visibility score. Results Elevated MDT coincided with suspected FLAIR‐positive FCD lesions in the majority of cases (5 out of 8 lesions). Ulegyria was also MDT‐positive, but heterotopias were not. MDT did not detect abnormalities in epilepsy surgery cases previously deemed MRI‐negative. In low‐grade gliomas, MDT and FLAIR findings were co‐localized; however, the MDT abnormalities were more conspicuous, and tumor‐associated signals were more distinct relative to FLAIR. MDT was helpful in visual demarcation of ischemia and glioma tumor‐associated signals in postoperative imaging. Significance MDT frequently aligns with the FLAIR signal, but MDT is visually more prominent. In the presurgical evaluation of epilepsy patients, it contributes to supporting existing or ambiguous findings. The very pronounced MDT signal in low‐grade gliomas might have the potential to be a visual aid in the diagnosis, treatment, and follow‐up of low‐grade gliomas. Plain Language Summary This is a pilot study that investigates a newly developed MRI technique called MDT imaging. The study shows that MDT helps identify brain lesions in patients with epilepsy. Finding brain lesions can improve the success of epilepsy surgery and help patients become seizure‐free. MDT imaging also helps visualize tumors in low‐grade glioma patients, which could improve surgical planning. These early findings suggest that MDT could be an additional useful tool for imaging in epilepsy surgery and low‐grade glioma patients, but more research is required to confirm its benefits.
Journals
2026 EN
Livanou Maria · Heneghan Anya · Bouliou Elli
+6 more
Abstract Eating disorders (EDs) present a chronic issue to child paediatric mental health services due to their high mortality and relapse rates. The transition from Child and Adolescent Mental Health Services to Adult Mental Health Services is a particularly high‐risk period for young people with EDs given their high vulnerability to change, which can negatively impact treatment outcomes. However, there is lack of evidence on the feasibility of inclusive and youth‐specific interventions that address the multiple and complex needs of this group during their transition to adult care. This proposed study aims to develop a newly introduced model of care called Transition for Eating Disorder Youth intervention (TEDYi) for young people aged 16–18 years with EDs transitioning from adolescent ED services to adult care. TEDYi will be co‐produced with young people, carers, and staff targeting interpersonal and psychosocial needs during the transition process. The first phase of the study involves interviews with young people ( N = 15) and carers ( N = 15) as well as focus groups with mental health professionals ( N = 15) across four ED adolescent and adult specialist services to explore their transition experiences. The second phase, consists of four Experience‐Based Co‐Design workshops, aimed at collaboratively developing and refining TEDYi.
Journals
2026 EN
Schnabel Jiana · Cooper Marita · Stedal Kristin
+5 more
ABSTRACT Objective Research suggests executive functioning (EF) inefficiencies contribute to anorexia nervosa (AN) onset and maintenance. Identifying EF subtypes in adolescents and adults with AN compared to healthy controls (HC) may provide insights into differences in illness severity, risk for prolonged illness, and highlight who could respond best to different treatments. Method We conducted secondary analysis of 751 participants: adolescents ( n = 559) and adults with AN ( n = 74), and adolescent HC ( n = 118). Latent profiles of six Delis Kaplan Executive Function System scores measuring EF constructs implicated in AN were derived. Differences across profiles on demographics, eating disorder cognitions (EDE/EDE‐Q score), BMI/BMI z ‐score, length of illness, weight suppression, and full‐scale IQ were examined. Results A three‐profile solution best fit the data: Profile 1 ( n = 324)—‘high verbal’, Profile 2 ( n = 349)—‘average’, and Profile 3 ( n = 78)—‘low flexibility and inhibition’. The low flexibility and inhibition profile comprised 10.6% of adolescents with AN, 30.0% of adults with AN, and 1.7% of adolescent HCs. Compared to other profiles, this profile was older, had a longer illness duration, higher EDE global scores, lower BMI z ‐scores, and lower full‐scale IQ scores. No profile differences emerged in BMI or EDE‐Q global scores. Discussion Only a small subset of our sample showed marked difficulties in flexibility and inhibition, challenging the notion that EF difficulties are a core feature of AN. Adolescents with AN in this profile showed greater illness severity, suggesting vulnerability to a more prolonged course of illness. These findings are a first step towards developing tailored treatment strategies based on EF profiles.
Journals
2026 EN
Rania Marianna · Irace Concetta · Sacco Raffaella
+6 more
ABSTRACT Objective Disturbances of glucose homoeostasis are claimed to act as both a consequence and maintaining factor in eating disorders (EDs). This study explored glucose trends and their association with real‐time food intake and self‐report eating psychopathology in a sample of patients with anorexia nervosa (AN) and binge‐eating disorder (BED). Method 30 patients (AN, 15; BED, 15) wore continuous glucose monitoring (CGM) sensors while synchronously collecting data on daily food intake. CGM outputs were extracted and correlated with nutritional intake, daily meals composition and self‐report eating psychopathology (BES, NEQ, GQ, Y‐FAS). Results Up to 74% of participants experienced hypoglycaemia in the study period, with unique trends by diagnosis (prolonged, interprandial, nocturnal episodes in AN; brief, postprandial, daytime episodes in BED). Significant association between the average number of daily meals, glucose coefficient of variation, and symptomatic events was evident in AN. Self‐report night eating and food addiction symptoms in AN, and self‐report grazing in BED, associated, respectively, with daytime and symptomatic hypoglycaemia. Conclusions Hypoglycaemia is a frequent finding in patients with AN and BED and is associated with daily meals composition and dysfunctional eating behaviours. Theoretical explanations are provided for a diagnosis‐specific effect on hypoglycemia events. CGM could valuably contribute to understanding, clinical staging, and customised treatments of EDs.
Journals
2026 EN
Yahdjian Laura · Campana Sofía · Tognetti Pedro M
+46 more
Rangelands are crucial to human well‐being, but their ability to provide ecosystem services is threatened. We (1) quantified key ecosystem services provided by rangelands, (2) assessed short‐ and long‐term impacts of fertilization (nutrient addition) and the exclusion of large grazing herbivores with fences (herbivore exclusion) on services, and (3) identified synergies and trade‐offs among services. We measured indicators of ecosystem services and plant diversity at 79 sites across six continents in the global Nutrient Network. Short‐term herbivore exclusion increased forage quantity and soil fertility, but longer‐term herbivore exclusion decreased both along with plant richness and pollination. Nutrient addition improved forage provisioning, soil stability, climate regulation, and control of soil erosion but lowered plant diversity and impeded delivery of related services, especially after prolonged application. We found synergies between plant diversity and pollination, as well as between soil fertility, soil stability, and climate regulation. Trade‐offs between forage stability and quality persisted after nutrient addition but disappeared with herbivore exclusion. Our results suggest that alternative management actions may sustain livestock production while maintaining rangeland ecosystem services.