ILAE-YES global webinar series: Integrating clinical and basic science in epilepsy research Cecilie G. Nome, Parthvi Ravat, Fabrice Bartolomei, Marco de Curtis, Rossella Di Sapia, Marian Galovic, Maria Gogou, Lukas Imbach, Julia Jacobs, Katja Kobow, Alice D. Lam, Christos Panagiotis Lisgaras, Elisa Micalizzi, Eleni Nikalexi, Jeffrey L. Noebels, Jeanne T. Paz, Avtar Singh Roopra, Sally Shaaban, Laurent Sheybani, Shobi Sivathamboo, Ana Suller Marti, Adam Williamson, Naoto Kuroda Epilepsia Open, 2026 Summary Bridging clinical and basic research is increasingly recognized as a priority in the epilepsy field, yet opportunities for integration remain limited by the time, space, and financial constraints of scientific meetings. To address this gap, the Research Task Force of the Young Epilepsy Section of the International League Against Epilepsy (ILAE‐YES) organized a free global webinar series designed to promote translational dialogue and provide accessible research education for early‐career clinicians, researchers, and physician‐scientists. Based on a preliminary ILAE‐YES community survey, eight topics of high interest were selected: (1) epigenetics, (2) EEG biomarkers, (3) ictogenesis, (4) thalamo‐cortical network, (5) sudden unexpected death in epilepsy, (6) neurodegeneration and seizures, (7) seizure‐related brain damage, and (8) neuromodulation therapy. From March to June 2025, eight live Zoom webinars were held, each featuring expert speakers representing both basic science and clinical perspectives, with recordings made available as unlisted YouTube videos to ensure on‐demand access. A total of 1199 individuals from 116 countries registered, 63.2% from low‐ and middle‐income countries. Live attendance averaged 50 participants per session, and the mean session duration was 71.6 min, including an average of 16 min of discussion. Post‐session feedback was obtained from 285 respondents; overall satisfaction was high, with 93.3% rating their experience as 4 or 5 on a 5‐point Likert scale. Speaker satisfaction was similarly high (95.4%), and 80.0% reported gaining new research ideas. Although access to YouTube and Google Forms may have limited participation in some regions, the series provided an inclusive and globally accessible platform. These findings demonstrated that free, discussion‐focused online webinars represent a scalable, low‐cost, and reproducible educational model that can effectively promote international engagement and integration between clinical and basic epilepsy research, aligning with the ILAE's global educational mission and complementing WHO IGAP priorities on capacity building and equitable access to knowledge. Plain Language Summary Bringing together basic science and clinical research is important for improving epilepsy care, but many researchers have limited opportunities to learn across these fields. We organized a free global webinar series that helped early‐career clinicians and researchers learn about epilepsy research by combining scientific talks with clinical perspectives and open discussion. More than 1100 participants from over 100 countries joined, and most reported high satisfaction and gaining new research ideas. These results show that free, discussion‐based online webinars can provide an accessible way to support research education and international learning in epilepsy.
Head to head comparison between arterial spin labelling MRI and [18F]FDG-PET in presurgical evaluation of epilepsy in children: the role of voxel-based asymmetry index analysis Pietro Mattioli, Giulia Nobile, Matteo Cataldi, Luca Bosisio, Francesco Famà, Andrea Rossi, Alessandro Consales, Stefano Raffa, Flavio Villani, Silvia Morbelli, Dario Arnaldi, Lino Nobili, Domenico Tortora, , Alessandra Ferrari, Stefano Francione, Thea Giacomini, Laura Giorgetti, Mattia Losa, Maria Margherita Mancardi, Valentina Marazzotta, Elisa Micalizzi, Mattia Pacetti, Irene Pappalardo, Costanza Parodi, Giulia Prato, Mariasavina Severino, Laura Siri, Andrea Michele Wolfler Neurological Sciences, 2026 Arterial Spin Labelling MRI is a neuroimaging technique able to evaluate brain perfusion, an indirect measure of brain metabolism and function. Arterial Spin Labelling MRI showed to have performances comparable to [18F]fluorodeoxyglucose-PET in in epilepsy, yet literature data is still lacking about its use in children and the value of voxel-based asymmetry index analysis. Purpose of the project is to compare the Arterial Spin Labelling MRI and [18F]fluorodeoxyglucose-PET ability to identify the epileptogenic zone before and after asymmetry index analysis in children. In this observational study, paediatric patients with focal onset drug-resistant epilepsy that underwent presurgical evaluation, including Arterial Spin Labelling MRI and [18F]fluorodeoxyglucose-PET, were enrolled. The epileptogenic zone was defined by anatomo-electroclinical correlation and post-surgical outcome, when feasible. The rates of concordance with the epileptogenic zone of Arterial Spin Labelling MRI and [18F]fluorodeoxyglucose-PET before (visual analysis) and after asymmetry index analysis, were calculated. Statistically significant differences between were determined using Mc Nemar’s test (p < 0.05). 28 paediatric patients (mean age 10.07 years, 15 females) with focal epilepsy were enrolled; 22 underwent epilepsy surgery (mean age 9.86 years, 12 females). When comparing the techniques, visual analysis of Arterial Spin Labelling MRI had a significantly lower rate of concordance with the epileptogenic zone (p < 0.05). Voxel-based asymmetry index analysis increased significantly the rate of concordance of Arterial Spin Labelling MRI with the epileptogenic zone, achieving results comparable with [18F]fluorodeoxyglucose-PET in a cohort of paediatric patients.
Peri-ictal respiratory dysfunction: Expanding the association between mTOR pathway disorders and ictal central apnea Margherita Burani, Giada Giovannini, Niccolò Orlandi, Matteo Pugnaghi, Leonardo Affronte, Mara Malerba, Lisa Taruffi, Laura Madrassi, Simona Scolastico, Alice Ballerini, Anna Elisabetta Vaudano, Irene Florindo, Enrico Ambrosini, Elisa Micalizzi, Gian Marco Duma, Elisa Osanni, Alberto Danieli, Fabiana Mambretti, Paolo Bonanni, Stefano Meletti Epilepsia, 2025 Among the etiologies of focal epilepsy, mutations of the GATOR1 complex genes—comprising NPRL3, NPRL2, and DEPDC5—are known to result in overactivation of mTORC1. A recent study highlighted an association between ictal and postictal central apnea (ICA) and pathogenic variants of DEPDC5. Here, we analyzed data from 134 patients across two independent cohorts diagnosed with focal epilepsy who underwent video‐electroencephalographic long‐term monitoring (VLTM) with cardiorespiratory polygraphy. Genetic testing results done for clinical–diagnostic purposes were reviewed in patients with epilepsy of unknown etiology and patients with magnetic resonance imaging (MRI)‐defined/suspected focal cortical dysplasia (FCD). In 46 patients, we recorded at least one seizure associated with ICA. Genetic testing was performed in 21 of 22 MRI‐negative patients with ICA, revealing variants in mTOR pathway genes in 10 cases (48%), including DEPDC5 (n = 6), NPRL3 (n = 3), and MTOR (n = 1). Regarding MRI‐positive patients with ICA (n = 24), an acquired lesional etiology was found in 11. Of 13 patients with MRI‐defined FCD, genetic testing was carried out in seven, all of whom had negative results. Moreover, no pathogenic variants were detected in the 14‐MRI negative patients without ICA. Our findings confirm that variants in mTOR pathway genes (not only in DEPDC5) are present in patients with ICA and underline the potential risk of sudden unexpected death in epilepsy. These results also highlight the importance of performing respiratory polygraphy during VLTM to document ictal apnea.
Persistent Postictal Central Apnea in Focal Seizures: Incidence, Features, and Imaging Findings Stefano Meletti, Margherita Burani, Alice Ballerini, Giada Giovannini, Elisa Micalizzi, Niccolò Orlandi, Lisa Taruffi, Niccolò Biagioli, Simona Scolastico, Laura Madrassi, Matteo Pugnaghi, Anna Elisabetta Vaudano Neurology, 2025 Background and Objectives Postconvulsive central apnea has emerged as a contributor to sudden unexplained death in epilepsy. The aim of this study was to evaluate the incidence and characteristics of postictal central apnea (PICA) in focal seizures. The secondary aim was to analyze morphometric features of the amygdala and other subcortical structures involved in autonomic control. Methods We prospectively enrolled consecutive patients admitted to the Epilepsy Monitoring Unit at Modena Academic Hospital (Italy) from April 2020 to December 2023. Inclusion criteria were as follows: (1) age older than 13 years; (2) at least 1 focal-onset seizure recorded during long-term video-EEG monitoring (LTVEM) with cardiorespiratory polygraphy. For each seizure, the presence of ictal central apnea (ICA) and/or PICA and its features were evaluated. Amygdala, hippocampus, thalamus, brainstem, and cerebellum volumetry were compared in patients with ICA/PICA with respect to healthy controls and patients with focal seizures without peri-ictal breathing disorders. Results A total of 69 patients (mean age 35.7 years; 42% female) with 406 focal-onset seizures were analyzed. ICA was recorded in 71 seizures (17%) in 27 patients. PICA was recorded in 24 seizures in 12 patients (10 with temporal lobe epilepsy) corresponding to 5.9% of all recorded seizures. Notably, PICA was observed only in seizures showing ictal apnea (in 33.8%). In 11 seizures with PICA, a single apneic event starting in the ictal and extending to the postictal period was observed. In 13 seizures, multiple apneic events were present in the postictal period (range 2–8). Seizures with PICA showed a longer peri-ictal apnea time (mean 75 seconds vs 40 seconds; p = 0.007) and a longer time to restore a regular rhythmic breathing after seizure termination (mean 173 seconds vs 42 seconds; p < 0.001) than seizures with self-limiting ictal apnea. Amygdala volumes ipsilateral to the epileptogenic zone were larger in patients with ICA/PICA compared with controls and patients without seizure-related apnea. Discussion PICA occurs in approximately 6% of focal seizures and is associated with extended apnea time and an enlarged amygdala ipsilaterally to the epileptogenic zone. Our data support the existence of a continuum from ictal to PICA and highlight the importance of cardiorespiratory recordings in LTVEM.
CASPR2-related epilepsy: A distinctive and unrecognized form of epilepsy in adult and elderly males Roberto Michelucci, Elena Pasini, Patrizia Riguzzi, Maria Tappatà, Maria Pia Giannoccaro, Elisa Micalizzi, Anastasia Lechiara, Pietro Mattioli, Luana Benedetti, Flavio Villani Epileptic Disorders, 2024 ObjectiveThe aim of this study was to describe the clinical features of contactin‐associated protein‐like 2 (CASPR2)‐IgG‐associated seizures.MethodsNine patients were retrospectively collected from two epilepsy centers. For each patient we obtained a full clinical, neurophysiological, and MRI study along with detection of antineuronal autoantibodies from serum and CSF. The patients were followed up for 1–6 years.ResultsThe patients were nine male subjects aged 56–85 years (mean: 66) with a 1‐ to 14‐year (mean: 6,3 median: 6) history of seizures. The seizures were classified as focal onset seizures with impaired awareness, usually preceded by epigastric aura (two), piloerection (two), olfactory hallucinations (two), nausea and dizziness (one). Tonic–clonic seizures were present in five patients. Seizure frequency was high in six cases and sporadic in three. Most patients reported memory impairment (eight) or behavioral/mood changes (four). Interictal EEGs usually showed bilateral or unilateral temporal epileptiform abnormalities. A number of seizures arising from the temporal lobes, with bilateral asynchronous onset, were recorded on long‐term video‐EEG monitoring in two patients. MRI disclosed nonspecific white matter T2 hyperintensities suggestive of chronic vascular changes in four patients and bilateral T2‐FLAIR amygdalo‐hippocampal hyperintensity in three cases. Neuropsychological study demonstrated various degrees of cognitive impairment in the majority of cases. Increased titers of CASPR2 autoantibodies were detected in the serum and CSF, which persisted over time in four cases. Drug resistance to common anti‐seizure medications was present in seven cases who benefited from immunotherapy.SignificanceCASPR2‐IgG testing should be performed among old male patients with a recent or even not recent onset of focal seizures with impaired awareness particularly when these seizures are accompanied by cognitive impairment or behavioral disturbances. In these cases, anti‐seizure medications may be ineffective while immunotherapy may lead to a prompt improvement of seizures and cognitive deficits.
A VAMS-based LC–MS/MS method for precise cenobamate quantification in epilepsy (patients) Federica Pigliasco, Alessia Cafaro, Sebastiano Barco, Margherita Biondi, Manuela Stella, et al. Epilepsia Open, 2024 OBJECTIVE: Cenobamate (CNB), a recently approved antiseizure medication by the European Medicines Agency (EMA), serves as an adjunctive therapy for focal-onset seizures in adult patients unresponsive to at least two other treatments. Administered in polytherapy, CNB can potentially interact with co-administered drugs in epilepsy patients, necessitating dose adjustments and the need for effective therapeutic drug monitoring (TDM). METHODS: In this study, we introduce a novel LC-MS/MS method for precise CNB quantification using Volumetric Absorptive Microsampling (VAMS), following validation according to ICH guidelines M10. VAMS samples are efficiently extracted with 200 μL of methanol, with chromatographic separation achieved using an Acquity UPLC HSS PFP column. The method's efficacy was confirmed through its application to real samples from adult CNB-treated patients. RESULTS: Our results demonstrate that the method exhibits linearity within the range of 0.05-30 mg/L, with intra- and inter-run precision ranging from 1% to 8% and accuracy from 1% to 10% based on 30 μL of sample. Furthermore, CNB stability in VAMS is confirmed for up to 15 days at 25°C and -20°C. Importantly, no significant difference was observed between CNB concentrations in VAMS samples and those in plasma obtained from venous blood. SIGNIFICANCE: This VAMS-based LC-MS/MS method presents a robust alternative for TDM in CNB-treated patients. Future investigations should explore CNB concentrations in capillary blood and assess their correlation with plasma levels to further enhance its clinical utility. PLAIN LANGUAGE SUMMARY: Cenobamate is an antiepileptic drug and used for treatment of focal-onset seizures in adult patients (≥18 age). TDM can prevent drug interactions and minimize drug toxicity. The aim of this work is to evaluate volumetric absorptive microsampling (VAMS) from capillary blood as an alternative strategy for TDM in patients treated with the newly antiepileptic drug. Our method is suitable for TDM, and this study suggests that VAMS allows monitoring of cenobamate concentration and can offer valuable support for personalized therapy in refractory epilepsy.
Adjunctive cenobamate in people with focal onset seizures: Insights from the Italian Expanded Access Program Roberta Roberti, Giovanni Assenza, Francesca Bisulli, Giovanni Boero, Laura Canafoglia, Valentina Chiesa, Carlo Di Bonaventura, Giancarlo Di Gennaro, Maurizio Elia, Edoardo Ferlazzo, Alfonso Giordano, Angela La Neve, Claudio Liguori, Stefano Meletti, Francesca Felicia Operto, Nicola Pietrafusa, Monica Puligheddu, Patrizia Pulitano, Eleonora Rosati, Ilaria Sammarra, Elena Tartara, Giampaolo Vatti, Flavio Villani, , Emilio Russo, Simona Lattanzi Epilepsia, 2024
Ictal and Postictal Central Apnea in DEPDC5 -Related Epilepsy Stefano Meletti, Gian Marco Duma, Margherita Burani, Alberto Danieli, Giada Giovannini, Elisa Osanni, Elisa Micalizzi, Fabiana Mambretti, Matteo Pugnaghi, Anna E. Vaudano, Paolo Bonanni Neurology Genetics, 2024
The role of the amygdala in ictal central apnea: insights from brain MRI morphometry Elisa Micalizzi, Alice Ballerini, Giada Giovannini, Maria Cristina Cioclu, Simona Scolastico, Matteo Pugnaghi, Niccolò Orlandi, Marcella Malagoli, Maurilio Genovese, Alessandra Todeschini, Leandra Giunta, Flavio Villani, Stefano Meletti, Anna Elisabetta Vaudano Annals of Clinical and Translational Neurology, 2024
