Background and purpose Neuropsychological assessment is essential in pediatric epilepsy care, yet its implementation in clinical practice remains insufficiently characterized. This study describes neuropsychological practices across Italian pediatric epilepsy centers. Methods A national, cross-sectional, online survey was conducted between December 2024 and March 2025 by the Italian League Against Epilepsy. The 59-item survey assessed professional profiles, clinical practices, use of technology, and training needs. Eligible participants were psychologists and neuropsychologists involved in pediatric epilepsy care. Results Twenty-three centers completed the survey (response rate 59.0%). Assessment was systematically integrated within multidisciplinary teams across diagnostic, treatment, and follow-up phases. Primary referral drivers were cognitive concerns, treatment effects, and neuropsychiatric comorbidities. Core cognitive domains were consistently assessed, though test selection varied substantially: most centers used flexible approaches, whereas 43.5% implemented standardized protocols. Screening for intellectual disability, attention-deficit/hyperactivity disorder, and learning disorders was widely applied, while severe intellectual disability evaluations relied primarily on qualitative methods. Tele-neuropsychology was used selectively for follow-up rather than primary evaluation. Conclusions This study provides the first comprehensive national mapping of pediatric epilepsy neuropsychology practices. Neuropsychological assessment is a well-established component of pediatric epilepsy care in Italy, broadly consistent with international recommendations. However, variability in organization and assessment practices highlights the need for harmonized protocols, increased resources, and specialized training. Multidisciplinary and flexible models, alongside the cautious integration of digital tools, may enhance care and improve long-term outcomes
Pathogenic variants in SCN2A cause dysfunction of the NaV1.2 voltage-gated sodium channel and are associated with neurodevelopmental disorders with or without epilepsy. Treatment of epilepsy in these patients is challenging and depends on whether the variant results in a gain (GoF) or loss of function (LoF). We describe a patient with the de novo SCN2A variant p.C258R presenting with therapy-resistant developmental and epileptic encephalopathy type 11 (DEE type 11). We aimed to electrophysiologically analyze the functional consequences of this mutation and to examine the in vitro properties of phenytoin, lamotrigine, and topiramate, which resulted in clinical improvement. Depending on the specific functional readout after transient expression in HEK293T cells, mutation C258R of NaV1.2 channels resulted in a mixed LoF and GoF phenotype. NaV1.2-C258R channels exhibited slower inactivation kinetics and a left-shifted voltage dependence of steady-state inactivation. Current density was reduced when expressed in HEK293T cells although single-channel conductance and maximal channel open probability were only marginally affected. During repetitive stimulation, mutated channels showed stronger cumulative inactivation, consistent with LoF. Phenytoin and lamotrigine caused use-dependent block, but lamotrigine was less effective for C258R compared with the wild type. Topiramate diminished the current density in both variants with less use-dependence. The C258R mutation impairs NaV1.2 function through both LoF and GoF mechanisms. Sodium channel blockers with a strong use-dependence, such as phenytoin, may be preferential for seizure control in such cases.
SLC33A1 mutation (Huppke-Brendel Syndrome) is a rare, autosomal recessive disorder associated with copper metabolism and characterized by global developmental delay, sensorineural hearing loss, congenital cataract and generalized hypotonia. We report two siblings under 6 years with novel SLC33A1 gene mutation, born from heterozygous parents. The first patient developed early onset drug-resistant epilepsy (DRE) secondary to the novel genetic mutation; the second patient did not develop seizures but shared several other phenotypic features of the syndrome, highlighting intrafamilial variation in seizure penetrance. On electroencephalography of the first patient with DRE, independent spike and wave discharges were noted in the temporoparietal region with generalized background slowing. Diffuse electrodecrement with overriding paroxysmal fast activity was correlated with seizure semiology. Neuroimaging revealed generalized cerebral and cerebellar atrophy, ex-vacuo ventriculomegaly, and bilateral chronic subdural collections. We describe a shared genetic mutation in two siblings and highlight their overlapping and distinct clinical features, management challenges, and complications with invasive neuromodulation. These cases expand the differential diagnosis of copper-related metabolic disorders. Practical implications Variable seizure penetrance in SLC33A1 related disorders could manifest as epileptic phenotypes.
Introduction Depression is the most frequent co-morbidity in persons living with epilepsy (PwE). In Rwanda, the prevalence of epilepsy ranges between 2.9 and 7.6% and the prevalence of any depression in PwE is more than 22%. This prospective interventional patient-centered study determined incidence and prevalence of depression in PwE and clinical outcomes of moderate to severe depression (MSD) in three rural sectors in Northern Rwanda. Methods PwE were enrolled between June 2018 and December 2018. At each three-monthly study visit, PwE were screened for depression with Patient Health Questionnaire-9 (PHQ-9). If positive, the Hamilton Depression Rating Scale (HDRS) was administered to quantify severity of depressive symptoms and confirm diagnosis of depression. PwE with MSD (PwED) were provided anti-depressants and followed for one year. Patient-centered interventions addressing social determinants of mental health were adopted. Results Of 304 PwE enrolled, 25 (8.2%) presented MSD during the study. At baseline. Prevalence of any depression and MSD was 27% and 4.3%. respectively. Incidence of any depression or MSD was 245 and 48/1.000 patient-years, respectively. Seizure frequency improvement was observed in both groups. HDRS scores for PwED were significantly reduced from 22.8 at baseline to 7.9 at 12-months follow-up. Access to dedicated epilepsy nursing staff and medication, psycho-education and income-generating initiatives proved beneficial. Conclusions Kinyarwanda PHQ-9 and HDRS versions were successfully deployed for screening and diagnosing depression symptoms in PwE in rural settings. Treatment of epilepsy and co-morbid depression improved clinical outcomes. Implementation of depression screening in routine health practice in Rwanda is warranted.
Objective:Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an established palliative therapy for drug-resistant focal epilepsy; however, its efficacy for epileptic spasms (ES) and the clinical utility of unilateral stimulation remain unclear. To address these issues, we report a case of drug-resistant focal epilepsy with ES treated with unilateral ANT-DBS. Case:An 18-year-old right-handed male with focal cortical dysplasia type I had long-standing drug-resistant epilepsy. Despite multiple resective and palliative surgeries-including right frontal disconnection, corpus callosotomy, right anterior temporal lobectomy, and vagus nerve stimulation-daily ES, weekly focal impaired consciousness seizures (FIC), and monthly focal-to-bilateral tonic-clonic seizures (FBTC) persisted. Presurgical evaluation suggested an epileptic focus in the left temporal lobe for FIC/FBTC. ANT-DBS was planned for seizure alleviation. Lead implantation on the right side was considered unfavorable because of marked postsurgical atrophy. Therefore, unilateral ANT-DBS lead implantation on the left side was performed. Results:After implantation, ES frequency transiently decreased (median 0.46 seizures/day) but later increased during follow-up. Stimulation was initiated on postoperative day 22. After the stimulation amplitude reached ≥2.0 mA (postoperative day 92), the median spasm frequency decreased again to 0.31/day, lower than the preoperative baseline of 0.75/day (58.1% reduction; p = 0.012). FIC frequency also decreased from 0.21/day to 0.09/day (60.0% reduction; p = 0.121). Significance:Unilateral ANT-DBS was associated with a clinically meaningful reduction in ES in this highly refractory case, suggesting a potential therapeutic role even when bilateral implantation is not feasible.
