Anna Falco

Objective: Lennox–Gastaut syndrome (LGS) is a developmental and epileptic encephalopathy defined by polymorphic seizures, intellectual disability (ID), and characteristic electroencephalographic (EEG) patterns. The applicability and biological validity of current electroclinical criteria remain debated. This study evaluated the concordance between clinical and electroclinical definitions of LGS and applied unsupervised clustering to identify data‐driven profiles within LGS. Methods: We retrospectively analyzed patients clinically fulfilling LGS criteria, with longitudinal electroclinical documentation and at least one sleep EEG. Patients meeting complete electroclinical criteria were compared with those meeting clinical criteria alone. Additionally, exploratory unsupervised K‐modes clustering and discriminant correspondence analysis were applied in adolescent and adult patients. Results: We included 105 patients (60.9% female), with a median age of 24 years (interquartile range = 16–35). Sixty‐nine patients (65.7%) met complete electroclinical criteria, yet neurodevelopmental features, seizure types, magnetic resonance imaging (MRI) findings, and treatment refractoriness were comparable to the clinically defined subgroup. K‐modes clustering ( n = 97 patients) identified three data‐driven electroclinical profiles. Cluster 1 comprised patients with the earliest seizure onset, profound intellectual and motor impairment, EEG background slowing, lower prevalence of generalized paroxysmal fast activity (GPFA), highest prevalence of structural etiologies, and lowest likelihood of meeting complete electroclinical criteria for LGS. Among clusters more frequently fulfilling complete electroclinical criteria, Cluster 2 represented an early onset profile with higher rates of ID, EEG background slowing, and high prevalence of polymorphic seizures. Cluster 3 included comparatively preserved patients, characterized by later onset, milder neurodevelopmental impairment, and higher frequency of normal MRI. Despite similar clinical severity, Cluster 1 patients had undergone fewer antiseizure medication trials. Significance: Exploratory data‐driven clustering identified clinically relevant electroclinical profiles that may help refine phenotypic stratification within clinically defined LGS. These included a severe GPFA‐underrepresented profile and two GPFA‐positive phenotypes differing in developmental severity, seizure profile, and age at onset.

Background/Objectives: The advent of disease modifying therapies (DMTs) for Spinal Muscular Atrophy (SMA) has highlighted the need for reliable tools to assess bulbar function in type I individuals. The Oral and Swallowing Abilities Tool (OrSAT) was originally developed to evaluate swallowing and feeding abilities in infants with SMA type I during the first two years of life. This study aimed to assess the applicability of the OrSAT in a cohort of children with SMA type I older than 2 years. Methods: Fifty-two children with genetically confirmed SMA type I, aged 2 to 12.6 years, were included. All participants had received at least one DMT, administered either soon after diagnosis or when treatment became available. Bulbar and feeding abilities were assessed using the OrSAT and results were grouped according to clinical subtype and feeding modality. Given the small sample size of the subgroups and the ordinal nature of OrSAT scores, comparisons between groups were performed using the non-parametric Kruskal–Wallis test. Results: At follow-up, 27 children were orally fed, 19 were exclusively tube-fed, and 6 were tube-fed but were also able to eat some food by mouth. The OrSAT scores reflect a wide spectrum of bulbar function from severe to no impairment. Most children who required exclusive tube-feeding at follow-up had already been tube-fed at treatment initiation, while a small number showed improvement in swallowing abilities and the partial recovery of oral feeding during follow-up. Conclusions: Our results suggest that the OrSAT, previously used only in the first two years of life, may also be applicable in older children to describe bulbar involvement and monitor changes over time. However, further studies are needed to refine the tool for this age group and to formally validate its use in older children with SMA type I. Its use may contribute to the longitudinal assessment of swallowing abilities and support rehabilitative management.