Neurocognitive, behavioral, and treatment burden as key predictors of parental stress in pediatric epilepsy Cinzia Correale, Mattia Mercier, Simona Cappelletti, Nicola Pietrafusa, Chiara Falamesca, et al. Epilepsia, 2025 ObjectiveParental stress in pediatric epilepsy is often linked to seizure‐related factors. However, less is known about the contribution of child cognitive functioning, behavioral symptoms, and treatment complexity to caregiver burden. This study aimed to investigate how these variables, along with sociodemographic factors, predict perceived parental stress.MethodsWe conducted a cross‐sectional study including 117 children with epilepsy and 149 caregivers. Cognitive functioning was classified through standardized assessments; behavioral symptoms were evaluated using the Child Behavior Checklist (CBCL); and parental stress was measured with the Parenting Stress Index–Short Form (PSI‐SF). Clinical variables included epilepsy etiology, seizure control, drug resistance, and medication regimen. Group comparisons and regression models were used to explore predictors of stress.ResultsHigher stress levels were observed among parents of children with moderate intellectual disability, compared to those with normal cognition. Clinical‐range behavioral symptoms—especially internalizing problems—were significantly associated with elevated stress across PSI domains. Parents of children receiving polytherapy or with drug‐resistant epilepsy reported higher levels of dysfunctional parent–child interaction. Lower educational attainment was also linked to greater stress. Although no stress differences emerged by caregiver gender, most participants were mothers. Notably, elevated Defensing Responding scores suggested a potential underreporting of caregiver burden.SignificanceThese findings indicate that child cognitive and behavioral characteristics, along with treatment complexity, play a greater role in parental stress than core epilepsy variables alone. It is notable that, the tendency to underreport stress may obscure caregiver needs, especially in clinical settings relying solely on self‐report measures. Routine caregiver screening and multimodal assessment strategies—including interviews and observations—should be integrated into epilepsy care pathways. Supporting caregiver well‐being is essential to sustaining family functioning. It aligns with the priorities outlined in the World Health Organization (WHO) Intersectoral Global Action Plan (IGAP), which highlights caregiver support as a key pillar of person‐ and family‐centered care for neurological conditions.
Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study Marina Trivisano, Ilaria Mosca, Licia Salimbene, Angela De Dominicis, Paolo Ambrosino, et al. Annals of Neurology, 2025 ObjectiveGain‐of‐function (GoF) variants in KCNT1 encoding for potassium channels are associated with different epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), other early infantile developmental and epileptic encephalopathies, and focal epilepsy. Fluoxetine blocks currents from both wild‐type (WT) and mutant KCNT1 channels with GoF in vitro features. In this study, we tested the hypothesis that treatment with fluoxetine might improve clinical outcome in patients with EIMFS carrying GoF variants in KCNT1 channels showing in vitro sensitivity to fluoxetine blockade.MethodsWe enrolled three pediatric patients carring de novo KCNT1 genetic variants linked to EIMFS. Functional and pharmacological studies to assess fluoxetine's ability to counteract in vitro variant‐induced functional effects were performed with patch‐clamp electrophysiology on heterologous channel expression in mammalian Chinese hamster ovary cells. Neuropsychological assessment, electroencephalogram and seizure diary were evaluated at baseline and every 3 months during the study. Electrocardiography and blood levels of medications were monitored for safety.ResultsAll 3 KCNT1 variants displayed GoF effects in vitro. Exposure to fluoxetine (10μM) blocked both WT and mutant KCNT1 channels, therefore, counteracting variant‐induced functional effects. Treatment with fluoxetine caused a variable reduction of seizure frequency (25–75%). Improvement in visual attention, participation, and muscle tone was also reported. No adverse events were reported except for transient dyskinesia in 1 patient, which was probably related to an increase in fluoxetine plasma level.InterpretationFluoxetine may be a potential targeted medication in EIMFS caused by KCNT1 GoF variants. Further research is needed to assess its long‐term efficacy and safety. ANN NEUROL 2025
Animal-Assisted Interventions in Paediatric Hospitals: An Investigation of Italian Healthcare Personnel Attitudes Cinzia Correale, Sofia Orlando, Marta Borgi, Simonetta Gentile, Simona Cappelletti Children, 2025 Background: Evidence of the beneficial effects of animal-assisted interventions (AAI) on patients admitted to paediatric hospitals is growing. However, there is still little information about healthcare professionals’ knowledge of and attitudes towards AAI, both as a complement to medical treatments and as a tool for improving the workplace environment. The present study explores the perspectives of Italian paediatric hospital staff after the onset of the COVID-19 pandemic. Methods: An online questionnaire was developed and distributed to paediatric hospital personnel across Italy. The questionnaire addressed topics including AAI’ impact on the hospital environment, their role as a resource for patients and families, their effect on staff well-being, and the perception of the feasibility of AAI implementation in hospitals. Data were analysed descriptively and qualitatively. Results: A total of 44 respondents took part in the survey. Most respondents agreed that AAI could improve hospital environments and serve as a valuable resource for patients and families. However, results were more mixed about the effects of AAI on staff well-being and the feasibility of their implementation. Qualitative analysis identified recurring themes including the positive impact of AAI on emotions/general well-being, improved compliance and treatment outcomes, and reduced stress and distress. Concerns included organisational/logistical challenges, hygiene issues, and potential impact on staff workload. Notably, most participants felt that the COVID-19 pandemic had not affected their perception of AAI safety. Conclusions: Most respondents viewed AAI favourably and supported their implementation as a means of benefiting patients and caregivers. Concerns mainly related to organisational and logistical barriers highlight areas that require further exploration in future research.
Unveiling the disease progression in developmental and epileptic encephalopathies: Insights from EEG and neuropsychology Paolo Surdi, Marina Trivisano, Angela De Dominicis, Mattia Mercier, Ludovica Maria Piscitello, et al. Epilepsia, 2024 ObjectiveDevelopmental and epileptic encephalopathies (DEEs) are neurological disorders characterized by developmental impairment and epilepsy. Our study aims to assess disease progression by comparing clinical findings, electroencephalography (EEG), and neuropsychological data from seizure onset to the last follow‐up evaluation.MethodsWe retrospectively reviewed patients with genetic DEEs who were followed‐up at the epilepsy unit of Bambino Gesù Children's Hospital, Rome. We collected information regarding gender, family history, genetic variant, age at onset and at last follow‐up, neurological examination, type of seizure, drug resistance, occurrence of status epilepticus, and movement and cognitive and behavioral disorders. We compared EEG background activity, epileptiform abnormalities, and cognitive functions between seizure onset and the last follow‐up evaluation using the McNemar‐Bowker test (α = 5%).ResultsA total of 160 patients (94 female) were included. Genetic analysis revealed a spectrum of pathogenic variants, with SCN1A being the most prevalent (25%). The median age at seizure onset and at the last follow‐up was 0.37 (interquartile range [IQR]: 0.09–0.75) and 8.54 years (IQR: 4.32–14.55), respectively. We documented a statistically significant difference in EEG background activity (p = .017) and cognitive impairment (p = .01) from seizure onset to the last follow‐up evaluation. No significant differences were detected for epileptiform abnormalities (p = .2). In addition, high prevalence rates were observed for drug resistance (81.9%), movement disorders (60.6%), behavioral and autism spectrum disorders (45%), neurological deficits (31.3%), and occurrence of status epilepticus (23.1%).SignificanceOur study provides evidence that a clinical progression may appear in genetic DEEs, manifesting as development or worsening of cognitive impairment and disruption of EEG background activity. These results highlight the challenging clinical course and the importance of early intervention and personalized care in the management of patients with DEEs.
Epilepsy surgery below the age of 5 years: Are we still in time to preserve developmental and intellectual functions? Simona Cappelletti, Cinzia Correale, Mattia Mercier, Giusy Carfi Pavia, Chiara Falamesca, et al. Epilepsia Open, 2024 ObjectiveThe aim of this study is to describe the pre‐ and post‐operative developmental and intellectual functions in a cohort of patients who underwent surgery for drug‐resistant epilepsy (DRE) before the age of 5 years.MethodWe retrospectively reviewed the medical records and neurodevelopmental assessments of a cohort of 80 surgically treated pediatric patients with DRE. We included patients if they had at least one pre‐ and one post‐surgical neuropsychological assessments; 27 met the inclusion criteria. We evaluated Developmental Quotient (DQ) and Intelligence Quotient (IQ) before and after surgery. We identified two groups based on psychological evaluation outcome: Group 1, with stable or improved developmental and intellectual functions, and Group 2, experiencing developmental and intellectual loss.ResultsThe mean age at seizure onset was 1.2 ± 1.0 years, and the mean age at surgery was 2.9 ± 1.2 years. At the last follow‐up (mean 4 years, SD ± 2), 19/27 (70%) patients were seizure‐ and drug‐free; 18/27 patients (67%) fit in Group 1, and 9/27 (33%) fit in Group 2. The mean age at surgery was 2.6 years (SD ± 1.1; range 1.2–5.1) in Group 1 and 3.4 years in Group 2 (SD ± 1.1; range 1.6–5.0). Group 1 had a lower pre‐operative DQ/IQ total score than Group 2 (median DQ/IQ respectively 82 vs 108, p = 0.05). Between pre‐ and post‐assessments, we found that in Group 1, Performance scores improved (82.7 vs 102, p = 0.001), while in Group 2, the Total and Verbal scores worsened (respectively 108 vs 75, p = 0.008, and 100 vs 76, p = 0.021).SignificanceOur study's results emphasize the positive impact of surgery before the age of 5 years on developmental and intellectual outcomes. Despite limitations such as a small sample size, lack of a control group, and diverse etiologies, our findings support the crucial role of early intervention in preserving or enhancing developmental and intellectual functions in young patients with DRE.Plain Language SummaryThis retrospective study, conducted at the Bambino Gesù Children Hospital in Italy, reports neuropsychological and developmental and/or cognitive data for children undergoing early epilepsy surgery (before the age of 5). It found that children with lower developmental or cognitive profiles gained the highest scores on post‐operative neuropsychological evaluations. This study provides information on the potential benefits of early surgery in shortening the duration of epilepsy, preventing or arresting deterioration, and enhancing plasticity and recovery.
Fenfluramine below the age of 2 years in Dravet syndrome: What about safety and efficacy? Nicola Pietrafusa, Marina Trivisano, Susanna Casellato, Cinzia Correale, Simona Cappelletti, et al. Epilepsia, 2024 Dravet syndrome (DS) is a rare developmental and epileptic encephalopathy. Infants with DS are especially vulnerable to the detrimental effects of prolonged and frequent seizures on development. Fenfluramine (FFA) is approved for the treatment of DS in patients aged 2 years and older. This study aims to evaluate the safety and efficacy of FFA in patients with DS younger than 2 years. We analyzed safety, tolerability, seizure, and neuropsychological outcome in a real‐world setting. Developmental profile was investigated using Griffiths Mental Development Scales (GMDS). Five patients received FFA at a mean age of 14.9 months (9.6–18.6). Median follow‐up was 13 months (interquartile range [IQR] = 12.9–24.4). All patients showed good tolerance to FFA. No significant variation of body mass index or echocardiographic issue was observed. Monthly median convulsive seizure frequency (MCSF) was 1.71 (IQR = 1.56–3.27) at the 6‐month baseline period and .92 (IQR = .43–1.28) at last follow‐up, with a median 54.43 (IQR = 40.91–60.83) percentage reduction in MCSF. Two of five patients had a performance improvement on GMDS subscales. Overall, the use of FFA below the age of 2 years in our small sample of patients was safe and represents a promising opportunity for seizure control and for protection of the neurodevelopmental outcome.
