Vagus nerve stimulation (VNS) is a therapy used for drug-resistant epilepsy, refractory status epilepticus and treatment-resistant depression. VNS can reduce seizure severity and frequency, improving quality of life. It is generally well tolerated, with rare complications, which can be early (surgical) or late (device-related or stimulation-related). Common side effects include vocal cord issues, cough, and infections. We present Horner syndrome as a rare complication of VNS caused by damage to the sympathetic innervation of the ipsilateral eye and characterized by ptosis, miosis and rarely anhidrosis. This was a case report and systematic review of the available literature according to PRISMA guidelines. The examined databases are Medline/PubMed, Scopus and Web of Science. A fourteen-year-old girl with drug-resistant epileptic encephalopathy and lissencephaly underwent VNS. Clinical signs of Horner syndrome appeared a few hours later. Our systematic review of the literature collected only three cases of Horner syndrome following VNS surgery out of 178 patients studied (one case report and two retrospective studies included in review). We report the fourth case in the literature, a case of permanent Horner.

Hemispherotomy is a neurosurgical procedure for treating refractory epilepsy, which entails disconnecting a significant portion of the cortex, potentially encompassing an entire hemisphere, from its cortical and subcortical connections. While this intervention prevents the spread of seizures, it raises important questions. Given the complete isolation from sensory-motor pathways, it remains unclear whether the disconnected cortex retains any form of inaccessible awareness. More broadly, the activity patterns that large portions of the deafferented cortex can sustain in awake humans remain poorly understood. We address these questions by exploring for the first time the electrophysiological state of the isolated cortex before and after surgery in ten awake pediatric patients. Post-surgery, the isolated cortex exhibited prominent slow oscillations (<2 Hz) and a broad-band shift in power spectral density from high to low frequencies. This resulted in a marked decrease of the spectral exponent, a validated consciousness marker, indicating broad-band slowing characteristic of unconscious states. When compared with a reference pediatric sample across the sleep-wake cycle, the spectral exponent of the contralateral cortex aligned with wakefulness, whereas that of the isolated cortex was consistent with deep NREM sleep. However, spindles did not emerge in the isolated cortex due to the lack of subcortical inputs, constituting a fundamental difference from physiological sleep. These findings demonstrate a unihemispheric sleep-like state during wakefulness, challenging the possibility that hemispherotomy might lead to inaccessible "islands of awareness." Moreover, the persistence of sleep-like patterns years after disconnection provides unique insights into the electrophysiological effects of disconnections in the human brain. ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: M.M. is co-founder and shareholder of Intrinsic Powers, Inc., a spin-off of the University of Milan Si.Sa. is advisor of the same company. The remaining co-authors have no conflicts of interest to declare.

Consciousness encompasses a range of cognitive and physiological states, including wakefulness, sleep, and altered states, as well as pathological conditions such as disorders of consciousness (DoC). In recent decades, quantitative EEG analysis has been used in adults to distinguish between wakefulness and sleep states and to study brain activity patterns associated with different DoC. However, such applications in pediatric subjects remain underexplored due to significant age-related changes in brain activity and limited data availability.The aim of this work was to develop a Support Vector Machine (SVM) classifier capable of distinguishing between wakefulness and sleep states in healthy pediatric subjects using a combination of linear and nonlinear EEG features. In addition, the feasibility of extending this classifier to pediatric patients with DoC was preliminarily evaluated.In 89 healthy pediatric subjects, 4 linear features (power spectral values in the canonical frequency bands: delta, theta, alpha, and beta) and 2 nonlinear features (spectral exponent and Higuchi fractal dimension) were computed from EEG data. SVM classifiers with different kernels (linear, polynomial and radial basis function) were trained and tested. The best classifier achieved an accuracy of 95% in distinguishing wakefulness from sleep states. Ignoring nonlinear features would reduce the accuracy by approximately 4%. In the pediatric DoC cohort, the SVM classifier showed that patients transitioning to a minimally conscious state had a gradual increase in the percentage of wakefulness-labeled EEG sweeps, while those who remained unresponsive had consistently low percentages.Clinical relevance— The proposed quantitative EEG analysis could potentially anticipate/assist the clinician's diagnosis of the change in the state of consciousness (from unresponsive wakefulness syndrome to minimally conscious state) in pediatric DoC patients.

The neuronal ceroid lipofuscinoses (NCLs) are incurable pediatric neurodegenerative diseases characterized by accumulation of lysosomal material and dysregulation of autophagy. Given the promising results of treatment with trehalose, an autophagy inducer, in cell and animal models of NCL, we conducted an open-label, non-placebo-controlled, non-randomized 12-month prospective study in NCL patients receiving oral trehalose (4 g/day). All were treated with a commercially available formulation for 6 months, followed by a 6-month washout. The primary endpoint was the presence of severe adverse reactions during treatment; secondary endpoints were clinical changes documented using the validated Unified Batten Disease Rating Scale and the Hamburg scale. Leveraging on our recent multiomic studies identifying convergent biomarkers in NCLs, fluid biomarker changes were taken as additional secondary endpoints. Of the 17 patients enrolled, 11 completed the study. Oral intake of trehalose in NCL patients with different genetic forms and at different disease stages was found to be well tolerated over 6 months. Oral trehalose is associated with subjective benefits reported by caregivers, but not with improvement or worsening on clinical scales. Analysis of potential biomarkers demonstrated significant differences between patients and controls at baseline, but we observed no modifications over time, or correlations with clinical scales and treatment. In our pilot experience in a heterogeneous disease group of NCL, oral trehalose seemed safe for patients. While subjective improvements were reported by caregivers, larger multicenter randomized placebo-controlled studies, and perhaps additional clinical tools covering multiple functions affected by the disease, will be needed to identify possible improvements in clinical scale scores and biomarkers.

Hemispherotomy is a neurosurgical procedure for treating refractory epilepsy, which entails disconnecting a significant portion of the cortex, potentially encompassing an entire hemisphere, from its cortical and subcortical connections. While this intervention prevents the spread of seizures, it raises important questions. Given the complete isolation from sensory-motor pathways, it remains unclear whether the disconnected cortex retains any form of inaccessible awareness. More broadly, the activity patterns that large portions of the deafferented cortex can sustain in awake humans remain poorly understood. We address these questions by exploring for the first time the electroencephalographic (EEG) state of the isolated cortex during wakefulness before and after surgery in 10 pediatric patients, focusing on non-epileptic background activity. Post-surgery, the isolated cortex exhibited prominent slow oscillations (<2 Hz) and a steeper broad-band spectral decay, reflecting a redistribution of power toward lower frequencies. This broad-band EEG slowing resulted in a marked decrease of the spectral exponent, a validated consciousness marker, reaching values characteristic of deep anesthesia and the vegetative state. When compared with a reference pediatric sample across the sleep-wake cycle, the spectral exponent of the contralateral cortex aligned with wakefulness, whereas that of the isolated cortex was consistent with deep NREM sleep. The findings of prominent slow oscillations and broad-band slowing provisionally support inferences of absent or reduced awareness in the isolated cortex. Moreover, the persistence of unihemispheric sleep-like patterns years after surgery provides unique insights into the long-term electrophysiological effects of cortical disconnections in the human brain.

Brain maturation from birth to adolescence involves profound transformations in neural dynamics, which can be studied in a minimally invasive manner using quantitative EEG. Most of the results published in the literature are based on spectral analysis approaches, which are extremely effective in detecting and assessing EEG rhythms. However, some aspects of EEG dynamics can only be investigated using nonlinear approaches, the use of which is still relatively unexplored in the pediatric population. The aim of the present paper is to assess the EEG differentiation of wakefulness from deep sleep (quiet sleep in neonates, stage N3 in older children) and its maturation across a wide developmental window (0-17 years) using the fractal dimension. Specifically, Higuchi fractal dimension (HFD) algorithm is used to analyse both wakefulness and sleep EEG recordings collected from 63 infants (aged 0-1 year) and 160 children (aged 2-17 years). To ensure methodological consistency, a data-driven criterion for the selection of HFD user parameters is implemented to enhance reproducibility. Our results show that HFD during wakefulness increases during the first year of life, followed by a stabilization or slight decrease in later years. In contrast, HFD during sleep exhibits a more stable profile, with only a mild increase over development. These findings are consistent with known neurodevelopmental processes-including synaptogenesis, pruning, and white matter maturation-and support the interpretation of HFD as a sensitive marker of large-scale integrative brain dynamics. These physiological trajectories of HFD both in wakefulness and sleep could be used as reference for future clinical applications in pediatric neurology and developmental monitoring.

OBJECTIVE:This study aimed to evaluate the efficacy and safety of adjunctive, highly purified Cannabidiol (Epidiolex®) in individuals with drug-resistant epilepsy (DRE) due to genetically determined typical Rett Syndrome (RTT) and CDKL5 Deficiency Disorder (CDD). METHODS:We recruited subjects with genetically confirmed typical RTT and CDD with drug-resistant seizures who received add-on treatment with highly purified Cannabidiol (CBD) through a national collaboration group. CBD treatment was titrated from 5 to 20 mg/kg/day; concurrent antiseizure medications (ASMs) could have been adjusted as clinically indicated. RESULTS:We enrolled 27 subjects (26 females), carrying a MECP2 genetic variant (14 subjects, 51.9%) or a CDKL5 genetic variant (13 subjects, 48.1%). Median age [IRQ] of individuals was 10.5 [7.9, 18.5] years. The median dose of CBD [IRQ] at last follow-up was 15 [11.12, 18.8] mg/kg/day, in association with a mean of 3 ASMs (range 2-4). The median duration of treatment was 14 [8.5, 20] months. Although not reaching a significant statistical effect, CBD reduced the incidence of seizures with respect to the baseline in 18/27 (66.6%) subjects, with 7 (25.9%) showing a seizure reduction >75%, and 11 (40.7%) >50%. The most relevant adverse events were somnolence seen in 3 subjects, irritability/agitation in 2 subjects, loss of appetite in 2 subjects, and insomnia in 1 individual. Caregivers reported an improvement in attention and reactivity in 12 subjects (44.4%), in sleep quality in 5 subjects (18.5%), and in motor aspects in 3 patients (11.1%). SIGNIFICANCE:CBD resulted effective in reducing seizure frequency in 66.6% of the study sample, regardless of the pathogenic variant; side effects were mild, and caregivers reported an improvement in behavioral and motor features. PLAIN LANGUAGE SUMMARY:This study explored the use of highly purified Cannabidiol (CBD, Epidiolex®) as an add-on therapy for individuals with drug-resistant epilepsy due to Rett Syndrome (RTT) or CDKL5 Deficiency Disorder (CDD). Twenty-seven participants received CBD alongside their usual ASMs. After a median treatment duration of 14 months, 66.6% experienced fewer seizures, with some showing over 75% reduction. Side effects were generally mild, mainly sleepiness or irritability. Notably, caregivers reported improvements in attention, responsiveness, sleep, and motor function. While results were not statistically significant, they suggest CBD may benefit seizure control and quality of life in RTT and CDD patients.

Hemispherotomy is a surgical procedure that disconnects a large portion of the cerebral cortex from cortical and subcortical inputs in patients with severe refractory epilepsy. Whether the disconnected cortex - inaccessible to behavioral assessment - supports consciousness remains unknown. Functional MRI studies have indicated preserved resting-state networks within the disconnected hemisphere, raising the possibility that it may represent an ‘island of awareness’. However, these networks can also persist in unconscious states, such as anesthesia and deep sleep. Here we assess the capacity of the disconnected cortex to support consciousness by exploring its electrophysiological state, before and after hemispherotomy, in ten awake pediatric patients. After surgery, the disconnected cortex–but not the contralateral cortex–entered a state dominated by slow oscillations (<2 Hz) resembling those observed during deep sleep; further, the spectral exponent, a previously validated marker of consciousness indexing the 1/f-like decay of the power spectral density, assumed values typically found in unconscious brain-injured and anesthetized adults. When compared to a reference pediatric sample, spectral exponent values were compatible with wakefulness in the contralateral cortex but attained levels typical of deep sleep over the disconnected cortex, suggesting that the disconnected cortex is not an island of awareness.

AbstractObjectivesPeople with neurodevelopmental disorders frequently experience sleep disturbances, negatively impairing their quality of life. We aimed to determine the prevalence and nature of sleep disturbances in patients with SCN8A‐related disorders.MethodsThrough a collaborative network of caregivers and clinicians, we collected data about epilepsy, cognitive/motor abilities, medications, and relevant comorbidities of patients harboring a pathogenic SCN8A variant. The Sleep Disturbance Scale for Children (SDSC), the Children's Sleep Habits Questionnaire (CSHQ‐22‐items), and the Pediatric Daytime Sleepiness Scale (PDSS) were distributed and evaluated by factor scores and Composite Sleep Index. Video‐EEG‐polysomnographic recordings were performed.ResultsWe enrolled 47 patients (age range: 2–39 years), whose phenotypes ranged from SCN8A‐DEE to intellectual disability without epilepsy. In the majority of them (82%), sleep disturbances were reported and/or observed at the SDSC. The most frequent were difficulty in initiating and maintaining sleep (64%), followed by sleep breathing disorder (43%), sleep–wake transition disorder (34%), and daytime sleepiness (34%). Sleep disturbances were more frequent in patients with severe DEE (96%) and ongoing seizures (93%) and were more severe in patients with sleep‐related seizures. The CSHQ and PDSS confirmed difficulty in initiating and maintaining sleep. Polysomnographic recordings (9 patients/20 nights) showed an altered sleep structure in 95%, with frequent arousals, mainly not seizure related.SignificanceMore than 80% of patients with SCN8A‐related disorders presented with sleep disturbances, primarily consisting of sleep instability with difficulty of initiating and maintaining sleep. Animal studies showed sleep disturbances in SCN8A‐ and SCN1A‐Dravet Syndrome mice models, suggesting a role for voltage‐gated sodium channels in the regulation of sleep. Understanding the effects of SCN8A dysfunction on sleep stability may guide future therapeutic efforts to alleviate this often distressing symptom also in seizure‐free SCN8A patients.Plain Language SummaryIn this study, we analyzed sleep disturbances in patients with disorders related to a genetic mutation in the gene SCN8A. We found that the majority of the patients experienced sleep disturbances, mainly consisting in difficulty of initiating and maintaining sleep. Sleep disturbances were more frequent in patients with severe cognitive impairment and active epilepsy and more severe in patients with seizures during sleep.

BackgroundEpilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and X-linked intellectual disability with epilepsy.Patients and MethodsData including demographic aspects, gene variants, seizure semiology and timing, EEG features, neuroimaging and response to therapy were retrospectively collected in patients with IQSEC2-related epilepsy referring to 8 Italian tertiary centres.ResultsThe reported cohort included 11 patients (8 males and 3 females). Mean age at the onset of epilepsy was 3.90±2.80 years. No cases were reported in the first year of life. No specific epileptic syndromes were recognized. Predominant seizure-types in the age range 12-36 months included focal onset tonic seizures with impaired awareness, myoclonic seizures, and late onset spasms. Generalized motor seizures were predominant in patients between 3 and 6 years and between 12 and 18 years while focal motor seizures with impaired awareness were the most represented types between 6 and 12 years. No patients experienced status epilepticus. EEG patterns included a delayed maturation of EEG organization, irregular focal or diffuse slow activity, multifocal or diffuse epileptiform abnormalities. No structural epileptogenic lesions were detected at MRI. Valproate, lamotrigine, clobazam, topiramate and levetiracetam were the most used antiseizure medication. Complete seizure freedom was achieved only in 2 patients.ConclusionsOnset of epilepsy after the first year of age, predominance of focal seizures with impaired awareness and generalized motor seizures, no pathognomonic underlying epileptic syndrome and infrequent occurrence of status epilepticus emerged as the main features of IQSEC2-related epilepsy phenotype.

This study investigates the respiratory abnormalities in Dravet Syndrome (DS) through a detailed case report and a narrative literature review. We report the case of a 4-year-old girl, harboring a de novo SCN1A mutation, who exhibited recurrent hypoxemic respiratory failure during febrile infections, not constantly associated with seizures or status epilepticus. In addition, a comprehensive review, including 21 cases, highlights the multifaceted nature of respiratory complications in DS. Notably, severe episodes could occur during common respiratory febrile infections, suggesting an association between DS and increased respiratory risk during febrile illnesses. In fact, the severity and persistence of hypoxemia, even during mechanical ventilation, suggest potential subacute respiratory impairment following seizures and/or infections. The proposed hypothesis of autonomic dysregulation could provide a framework for understanding the intricate relationship between neurological, cardiac, and respiratory functions in DS. This study emphasizes the need for tailored clinical management during febrile illnesses, considering the potential for apnea-related arrhythmias and challenging-to-treat hypoxemia. Further research, including longitudinal studies and advanced physiological monitoring, is crucial for refining our understanding and informing targeted interventions for respiratory abnormalities in DS.

Purpose The objective of this study is to characterize the electro-clinical phenotype of individuals affected by the rare PPP3CA gene-related developmental and epileptic encephalopathy (DEE). Methods We provide a detailed electro-clinical description of four previously unreported subjects, with unremarkable structural brain MRI and a normal screening for inborn errors of metabolism, who carry pathogenic variants within the regulatory domain of the PPP3CA gene, which encodes for calcineurin. We also conducted a literature review via PubMed and SCOPUS (up to December 2023) to collect all the studies reporting clinical details of subjects with PPP3CA pathogenic variants within the regulatory domain. Results Our in-depth investigation reveals two distinct electro-clinical phenotypes with unique interictal and ictal patterns. Pathogenic variants within the calmodulin-binding domain result in childhood-onset epilepsy with focal and generalized seizures, developmental and intellectual impairments. Pathogenic variants within the regulatory domain lead to early onset drug-resistant severe epilepsy and potentially fatal outcomes. Comparative analysis with existing literature corroborates the notion that truncating mutations, prevalent in the regulatory domain but also possible in the calmodulin-binding domain, consistently associate with more profound disabilities and drug-resistant epilepsy. Conclusion Our study emphasizes the critical role of pathogenic variants’ type and location on the severity of PPP3CA-related DEE. We also speculate, based on peculiar EEG patterns, on potential pathophysiological mechanisms involving calcineurin dysfunction and calcium homeostasis. In order to improve our understanding of this rare DEE, we need both collaborative efforts to gather larger cohorts and further experimental studies.

Background: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE. Methods: We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up. Results: We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE. Discussion and Conclusions: Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS’s potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights.

Introduction: Vagus nerve stimulation (VNS) is a neuromodulation therapy for drug-resistant epilepsy (DRE), refractory status epilepticus, and treatment-resistant depression. The lead is tunneled into the subcutaneous space and connected to the generator, which is usually implanted in a subcutaneous pocket below the clavicle. Surgical complications in the chest region include skin breakdown or infection. An alternative approach is to perform a subclavear subpectoral implantation. In our surgical series, we report a new aesthetic implantation method for VNS generators in children and young patients: the transaxillary subpectoral placement. Materials and methods: From May 2021 to May 2023,10 vagus nerve stimulation generators were placed subpectorally with a transaxillary approach by the authors. We considered operative time, surgical complications such as blood loss, infections, device migration, pain, and adverse events at follow-up. Results: In this surgical series, we reviewed all cases of subpectoral implantation of VNS generators in children and young adults at our institution in the last 2 years. All patients were treated with subpectoral Sentiva 1000 (Livanova PLC) insertion with axillary access by a neurosurgeon and a pediatric surgeon. The operative time was slightly longer compared to the traditional subcutaneous implant. All generators reported impedances within the optimal range. Blood loss was not significant and no other perioperative complications were reported. Patients and families were highly satisfied with the outcomes in terms of comfort and aesthetic results after surgery and at the last follow-up. No cases of infection occurred, and no malfunctions or displacements of the generator were registered at clinical follow-up. Conclusion: The transaxillary subpectoral placement of theVNS generator is an aesthetic and anatomic approach, which provides several benefits to children and young adults. (c) 2023 Elsevier Inc. All rights reserved.

During development, the brain undergoes radical structural and functional changes following a posterior-to-anterior gradient, associated with profound changes of cortical electrical activity during both wakefulness and sleep. However, a systematic assessment of the developmental effects on aperiodic EEG activity maturation across vigilance states is lacking, particularly regarding its topographical aspects. Here, in a population of 160 healthy infants, children and teenagers (from 2 to 17 years, 10 subjects for each year), we investigated the development of aperiodic EEG activity in wakefulness and sleep. Specifically, we parameterized the shape of the aperiodic background of the EEG Power Spectral Density (PSD) by means of the spectral exponent and offset; the exponent reflects the rate of exponential decay of power over increasing frequencies and the offset reflects an estimate of the y-intercept of the PSD. We found that sleep and development caused the EEG-PSD to rotate over opposite directions: during wakefulness the PSD showed a flatter decay and reduced offset over development, while during sleep it showed a steeper decay and a higher offset as sleep becomes deeper. During deep sleep (N2, N3) only the spectral offset decreased over age, indexing a broad-band voltage reduction. As a result, the difference between values in deep sleep and those in both light sleep (N1) and wakefulness increased with age, suggesting a progressive differentiation of wakefulness from sleep EEG activity, most prominent over the frontal regions, the latest to complete maturation. Notably, the broad-band spectral exponent values during deep sleep stages were entirely separated from wakefulness values, consistently across developmental ages and in line with previous findings in adults. Concerning topographical development, the location showing the steepest PSD decay and largest offset shifted from posterior to anterior regions with age. This shift, particularly evident during deep sleep, paralleled the migration of sleep slow wave activity and was consistent with neuroanatomical and cognitive development. Overall, aperiodic EEG activity distinguishes wakefulness from sleep regardless of age; while, during development, it reveals a postero-anterior topographical maturation and a progressive differentiation of wakefulness from sleep. Our study could help to interpret changes due to pathological conditions and may elucidate the neurophysiological processes underlying the development of wakefulness and sleep.

Deidentifying MRIs constitutes an imperative challenge, as it aims at precluding the possibility of re-identification of a research subject or patient, but at the same time it should preserve as much geometrical information as possible, in order to maximize data reusability and to facilitate interoperability. Although several deidentification methods exist, no comprehensive and comparative evaluation of deidentification performance has been carried out across them. Moreover, the possible ways these methods can compromise subsequent analysis has not been exhaustively tested. To tackle these issues, we developed AnonyMI, a novel MRI deidentification method, implemented as a user-friendly 3D Slicer plugin-in, which aims at providing a balance between identity protection and geometrical preservation. To test these features, we performed two series of analyses on which we compared AnonyMI to other two state-of-the-art methods, to evaluate, at the same time, how efficient they are at deidentifying MRIs and how much they affect subsequent analyses, with particular emphasis on source localization procedures. Our results show that all three methods significantly reduce the re-identification risk but AnonyMI provides the best geometrical conservation. Notably, it also offers several technical advantages such as a user-friendly interface, multiple input-output capabilities, the possibility of being tailored to specific needs, batch processing and efficient visualization for quality assurance.

Objective: Patients with epilepsy are at risk for several lifetime problems, in which neuropsychological impairments may represent an impacting factor. We evaluated the neuropsychological functions in children suffering from three main epilepsy categories. Further, we analyzed the longitudinal evolution of the neuropsychological profile over time. Methods: Patients undergoing neuropsychological evaluation at our Department from 2012 to 2018 were identified retrospectively. We selected patients aged 6-16 years and with at least two evaluations. Three epilepsy categories were considered: focal/structural, focal self-limited, and idiopathic generalized. Each evaluation included the same structured assessment of main neuropsychological domains. The effect of the epilepsy category, illness duration, seizure status, and medication was computed in multilevel models. Results: We identified 103 patients (focal self-limited = 27; focal/structural = 51; and idiopathic generalized = 25), for 233 evaluations. The majority of deficits were reported in attention and executive functions (>30% of patients); the results were dichotomized to obtain global indexes. Multilevel models showed a trend toward statistical significance of category of epilepsy on the global executive index and of illness duration on global attention index. Illness duration predicted the scores of executive and attention tasks, while category and medication predicted executive task performance. Focal/structural epilepsies mostly affected the executive domain, with deficits persisting over time. By contrast, an ameliorative effect of illness duration for attention was documented in all epilepsies. Conclusions: This study offers lacking information about the evolution of deficits in time, the role of epilepsy category, and possible psychological implications for high-order cognitive skills, central in several social and academic problems.

Objective The aim of this study was to evaluate the ability of the Mini-Mental State Pediatric Examinations (MMSPE) in the individuation of neuropsychological impairments. Method MMSPE was administered to 60 children attending a primary or lower secondary school suffering from neurological diseases, admitted to our neuropsychology services. All children performed both a MMSPE examination and a neuropsychological evaluation. Results of neuropsychological evaluation and MMSPE were dichotomized. Positive predictive value (PPV), negative predictive value (NPV), and accuracy were also calculated. Results The diagnostic performance of MMSPE showed a good overall accuracy (0.83, CI 95% 0.64-0.91), NPV (0.81, CI 95% 0.73-1.00), PPV (0.87, CI 95% 0.68-0.94), specificity (0.91, CI 95% 0.81-1.00), sensitivity (0.74, CI 95% 0.57-0.90), and odds ratio of 28.5 (CI 95% 6.6-123), p < 0.001. Conclusions MMSPE has a good prognostic ability in predicting neuropsychological problems in the context of different neurological pediatric diseases. We suggest that this instrument could greatly improve pediatric clinical practice in identifying high-risk children.