Scopus Publications
- Validation of the MOG-AR Score
Sara Carta, Riccardo Tiberi, Nicola De Rossi, Giorgia Teresa Maniscalco, Giacomo Greco, et al.
Neurology Neuroimmunology and Neuroinflammation, 2026 - Cost-effectiveness of fenfluramine as add-on treatment in the management of Dravet Syndrome: A real-world multicenter study
Paolo A. Cortesi, Carla Fornari, Alessandra Boncristiano, Rita Facchetti, Simona Balestrini, et al.
Epilepsia Open, 2026
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. - National survey on the prevalence of single-gene aetiologies for genetic developmental and epileptic encephalopathies in Italy
Davide Mei, Simona Balestrini, Elena Parrini, Antonio Gambardella, Grazia Annesi, et al.
Journal of Medical Genetics, 2025
Background We aimed to estimate real-world evidence of the prevalence rate of genetic developmental and epileptic encephalopathies (DEEs) in the Italian population over a 11-year period. Methods Fifteen paediatric and adult tertiary Italian epilepsy centres participated in a survey related to 98 genes included in the molecular diagnostic workflows of most centres. We included patients with a clinical diagnosis of DEE, caused by a pathogenic or likely pathogenic variant in one of the selected genes, with a molecular diagnosis established between 2012 and 2022. These data were used as a proxy to estimate the prevalence rate of DEEs. Results We included 1568 unique patients and found a mean incidence proportion of 2.6 patients for 100.000 inhabitants (SD=1.13) with consistent values across most Italian regions. The number of molecular diagnoses showed a continuing positive trend, resulting in more than a 10-fold increase between 2012 and 2022. The mean age at molecular diagnosis was 11.2 years (range 0–75). Pathogenic or likely pathogenic variants in genes with an autosomal dominant inheritance pattern occurred in 77% (n=1207) patients; 17% (n=271) in X-linked genes and 6% (n=90) in genes with autosomal recessive inheritance. The most frequently reported genes in the survey wereSCN1A(16%), followed byKCNQ2(5.6%) andSCN2A(5%). Conclusion Our study provides a large dataset of patients with monogenic DEE, from a European country. This is essential for informing decision-makers in drug development on the appropriateness of initiatives aimed at developing precision medicine therapies and is instrumental in implementing disease-specific registries and natural history studies. - Seizures influence sleep macrostructure and the sleep–wake circadian rhythm in Dravet syndrome
Alberto Cossu, Jacopo Proietti, Ludovica Ghobert, Livia Rinaldi, Bernardo Dalla Bernardina, et al.
Epilepsia, 2025
ObjectiveDravet syndrome (DS) is a developmental and epileptic encephalopathy with a wide spectrum of comorbidities comprising sleep disorders, reported in up to 85% of cases. For this, a sleep study is recommended in patients with a sleep complaint. However, no data are available on sleep architecture in DS or on the impact of seizures on sleep quality and macrostructure. We aim to investigate the impact of epileptic phenomena on sleep in DS.MethodsIn this study, we report seizure type and frequency, seizures during sleep, and concomitant antiseizure medications (ASMs) of 30 patients with clinical diagnosis of DS and confirmed SCN1A pathogenic variant. We obtained 62 whole‐night polygraphic sleep recordings (PSGs) and analyzed sleep stages duration, number of arousal events (AEs), arousal index (AI), and number and number/hour of AEs preceded by interictal epileptiform discharges (IEDs; IED‐related arousals [IRAs]). In a subgroup of patients, actigraphic recordings and caregiver‐reported Sleep Disturbance Scale for Children (SDSC) questionnaires were collected.ResultsMean age at PSG was 9.9 years (range = 1.2–20.8). Mean sleep efficiency was 92.9%, mean AI was 4.2, and the mean IRA index was .5. Patients with tonic seizures during sleep had shorter rapid eye movement sleep duration (p < .05), and those with convulsive seizures during sleep had shorter N3 duration (p < .05). Higher IRA index was also associated with lower total N3 duration (p < .05). In the recordings obtained during treatment with fenfluramine, IRAs were absent (p < .05) or less abundant (p < .05). The actigraphy parameters showed unstable sleep and correlated with PSG‐derived data.SignificanceOur study shows a significant effect of epileptic phenomena on sleep macrostructure in DS. Motor seizures and IEDs influence slow wave sleep, which could be one of the mechanisms that sustain encephalopathy in DS. Interestingly, fenfluramine seems to have a protective effect on this mechanism, both by stabilizing sleep and as an ASM. - Delphi consensus finding on paediatric-adult transition: results from the epilepsy transition working group of the italian league against epilepsy (LICE)
F. Darra, P. Biermann Klaus, D. Audenino, F. Bisulli, A. Cossu, et al.
Neurological Sciences, 2025
Purpose and rationale The care for paediatric and transitional-age epilepsy patients has expanded significantly, addressing the diverse needs of patients with self-limiting to lifelong conditions. Approximately one-third of patients with childhood-onset epilepsy remain dependent on parental care, with transition influenced by factors such as seizure frequency, drug resistance, comorbidities, and developmental disabilities. The Italian League Against Epilepsy (LICE) initiated a Delphi consensus to establish common guidelines for effective transition practices. Methods The consensus process included a literature review, thematic analysis, and iterative surveys using the Delphi Technique. The surveys involved 15 clinicians from LICE centres, forming the Epilepsy Transition Working Group (ETWG), and external experts. The surveys gathered expert opinions, with questions designed from evidence-based thematic areas. Results The Delphi rounds revealed several findings. Effective pediatric-to-adult transition in epilepsy requires a multidisciplinary approach, including child and adolescent neuropsychiatrists, continuous training for healthcare providers, and active involvement of caregivers. The transition process should start at variable ages depending on the type of epilepsy and associated comorbidities, and it should mitigate risk factors and address psychological stress for patients and caregivers. Items related to transition tools did not reach consensus, highlighting the need for standardized screening questionnaires and measurable outcomes. Conclusions This study emphasizes the necessity of an organized transition model involving various specialists and a tailored timeline. The consensus underscores the importance of caregiver involvement and unified educational curricula for all epileptologists to ensure effective care transition. The ETWG is building and improving a network of epilepsy centres to implement the organizational model derived from this study. - Real-Life Evaluation of the MOGAD Diagnostic Criteria: Application Challenges and Discrepancies
Sara Carta, Elia Sechi, Alessandro Dinoto, Chiara Mancinelli, Giacomo Greco, et al.
Neurology Neuroimmunology and Neuroinflammation, 2025 - Fenfluramine treatment for Dravet syndrome: Long term real-world analysis demonstrates safety and reduced health care burden
Alessandra Boncristiano, Simona Balestrini, Viola Doccini, Nicola Specchio, Nicola Pietrafusa, et al.
Epilepsia, 2025
ObjectiveFenfluramine (FFA), stiripentol (STP), and cannabidiol (CBD) are approved add‐on therapies for seizures in Dravet syndrome (DS). We report on the long‐term safety and health care resource utilization (HCRU) of patients with DS treated with FFA under an expanded access program (EAP).MethodsA cohort of 124 patients received FFA for a median of 2.8 years (34.4 months). We compared data on safety and HCRU during FFA treatment with those from a same pre‐treatment period. Echocardiography was conducted every 6 months. Information collected included gender, age, and auxological parameters (height, weight, and body mass index [BMI]) at the start (T0) and follow‐up (T1); FFA treatment details (start, withdrawal, dosage); adverse events (AEs); and HCRU data including hospital admissions, status epilepticus (SE) episodes, and rescue medication use. We grouped patients by weight: ≤37.4 kg (n = 68, 54.8%) and ≥37.5 kg (n = 56; 45.1%), with FFA dosing adjusted accordingly. Statistical analyses included paired t test, Wilcoxon signed‐rank test, Kaplan–Meier analysis, and Bonferroni correction to adjust for multiple testing.ResultsMean age was 47 months at clinical diagnosis and 81 months at T0. The last follow‐up average FFA dose was .5 mg/kg/day, with a median of .4 mg/kg/day. FFA led to a 9.5% reduction in prior treatment load. At last follow‐up, 118 of 124 (91.5%) remained on FFA. Rescue medication use decreased significantly from 4.5 to 1, hospitalizations from 1 to 0, and SE episodes from 0–240 to 0–180 (p < .001 for all). Seizure freedom was achieved in 9 of 118 patients (7.6%). AEs occurred in 39 of 124 patients (31.5%), with no cardiac issues or deaths. There was an overall mean reduction in BMI, with no statistical significance, and never requiring FFA withdrawal.SignificanceFFA is well tolerated, without cardiac toxicity, and reduces treatment load and HCRU, suggesting improved patient management. BMI reduction in young children highlights the need for growth and nutritional monitoring. - Quantitative EEG biomarkers for STXBP1-related disorders
Alberto Cossu, Francesca Furia, Jacopo Proietti, Caterina Ancora, Chiara Reale, et al.
Epilepsia, 2024
ObjectiveEEG patterns and quantitative EEG (qEEG) features have been poorly explored in monogenic epilepsies. Herein, we investigate regional differences in EEG frequency composition in patients with STXBP1 developmental and epileptic encephalopathy (STXBP1‐DEE).MethodsWe conducted a retrospective study collecting electroclinical data of patients with STXBP1‐DEE and two control groups of patients with DEEs of different etiologies and typically developing individuals matched for age and sex. We performed a (1) visual EEG assessment, (b) qEEG analysis, and (c) electrical source imaging (ESI). We quantified the relative power (RP) of four frequency bands (α β, θ, δ), in two electrode groups (anterior/posterior), and compared their averages and dynamics (standard deviation [SD] over time). The ESI was performed by applying the standard Distributed Source Modeling algorithm.ResultsWe analyzed 42 EEG studies in 19 patients with STXBP1‐DEE (10 female), with a median age at recordings of 9.6 years (range 9 months to 29 years). The δRP was higher in recordings of STXBP1‐DEE (p < .001) compared to both control groups, suggesting the pathogenicity and STXBP1‐specificity of these findings. In STXBP1‐DEE, the δRP was significantly higher in the anterior electrode group compared to the posterior one (p = .003). There was no correlation between the anterior δRP and the epilepsy focus, age at recordings, and concomitant medications The ESI modeling of this activity showed a widespread involvement of the dorsomesial frontal cortex, suggesting a large corticosubcortical pathologic network. Finally, we identified two groups of recordings: cluster.1 with higher anterior δRP and low dynamics and cluster.2 with lower δRP and higher dynamics. Patients in cluster.1 had a more severe epilepsy and neurological phenotype compared to patients in cluster 2.SignificanceThe qEEG analysis showed a predominant frontal slow activity as a specific STXBP1 feature that correlates with the severity of the phenotype and may represent a biomarker for prospective longitudinal studies of STXBP1‐DEE. - Clinical Reasoning: Hyperventilation-Induced Alternating Hemiplegia With Concomitant Hemispheric EEG Slowing in a 7-Year-Old Girl With Headache
Jacopo Proietti, Rita Di Censo, Silvia Spolverato, Alberto Cossu, Alessandra Bucci, et al.
Neurology, 2024 - Let the EEG speak my language: Italian translation of Standardized Computer-based Organized Reporting of EEG (SCORE)
Bruna Nucera, Fabrizio Rinaldi, Fedele Dono, Giacomo Evangelista, Stefano Consoli, et al.
Epileptic Disorders, 2023 - Adaptive behaviour in adolescents and adults with Dravet syndrome
Tommaso Lo Barco, Francesca Offredi, Eva Castino, Jacopo Proietti, Alberto Cossu, et al.
Developmental Medicine and Child Neurology, 2023 - PRRT2 benign familial infantile seizures (BFIS) with atypical evolution to encephalopathy related to status epilepticus during sleep (ESES)
A. Cossu, J. L. Santos, Giulia Galati, M. Nikanorova, P. Costa, et al.
Neurological Sciences, 2023 - Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey
A. Cossu, T. Lo Barco, J. Proietti, B. Dalla Bernardina, G. Cantalupo, et al.
Epilepsy and Behavior, 2023 - Gelastic seizures and “smiling spasms”: A peculiar ictal pattern
Tommaso Lo Barco, Laura Corona, Roberta Solazzi, Elena Fiorini, Giulia Galati, et al.
Epileptic Disorders, 2023 - Electric Source Imaging in Presurgical Evaluation of Epilepsy: An Inter-Analyser Agreement Study
Pietro Mattioli, Evy Cleeren, Levente Hadady, Alberto Cossu, Thomas Cloppenborg, et al.
Diagnostics, 2022 - Remote Teamwork Management of NORSE During the COVID-19 Lockdown
Alberto Cossu, Tommaso Lo Barco, Francesca Darra, Elena Fontana, Elena Fiorini, et al.
Neurology Clinical Practice, 2021 - Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real-world study
Nicola Specchio, Nicola Pietrafusa, Viola Doccini, Marina Trivisano, Francesca Darra, et al.
Epilepsia, 2020 - Simultaneous wireless and high-resolution detection of nucleus accumbens shell ethanol concentrations and free motion of rats upon voluntary ethanol intake
G. Rocchitta, A.T. Peana, G. Bazzu, A. Cossu, S. Carta, et al.
Alcohol, 2019
