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Flammable liquids typically adopted in chemical and industrial processes can be subjected to intense heat radiation due to nearby hot surfaces or fires. A second cascading event is then likely because the flash point can be easily reached and the surrounding environment can provide sufficient energy for ignition. Nevertheless, the flaming condition is not necessarily reached instantaneously if no direct (e.g., spark) ignition is present. Hence, a time to flaming, i.e., in the absence of an ignition source, is extremely relevant for the active and passive fire protection of flammable liquid, as the minimum time for intervention can be defined before developing a pool fire and for the correct evaluation of domino effects, in analogy with gas fires. In addition, a complete characterization of liquid behaviour under radiant heating is essential to guarantee safe operations, prevention measures, robust databases and optimized design. Therefore, this work reports the results for three liquid solvent representative classes of substances: i) hexane, ii) ethyl acetate, and iii) ethanol. A bench scale facility was adopted for the characterization of mass and energy aspects involving a pool fire of the investigated substances. Among the others, the ignitability and the intensity of the generated pool fires were evaluated experimentally in terms of mass burning rate, heat release rate, and combustion efficiency. Different boundary conditions were tested to identify the optimized set of conditions for a robust evaluation of the safety aspects of liquid. Results showed the most relevant trends in terms of ignitability of liquid species and combustion intensity during the pseudo-steady state regime of a pool fire. In addition, indications on the boundary conditions to be considered for a robust and consistent dataset were provided in this work.

Background and objectivesBRAT1 encephalopathy is an ultra-rare autosomal recessive neonatal encephalopathy. We delineate the neonatal electroclinical phenotype at presentation and provide insights for early diagnosis.MethodsThrough a multinational collaborative, we studied a cohort of neonates with encephalopathy associated with biallelic pathogenic variants in BRAT1 for whom detailed clinical, neurophysiologic, and neuroimaging information was available from the onset of symptoms. Neuropathologic changes were also analyzed.ResultsWe included 19 neonates. Most neonates were born at term (16/19) from nonconsanguineous parents. 15/19 (79%) were admitted soon after birth to a neonatal intensive care unit, exhibiting multifocal myoclonus, both spontaneous and exacerbated by stimulation. 7/19 (37%) had arthrogryposis at birth, and all except 1 progressively developed hypertonia in the first week of life. Multifocal myoclonus, which was present in all but 1 infant, was the most prominent manifestation and did not show any EEG correlate in 16/19 (84%). Video-EEG at onset was unremarkable in 14/19 (74%) infants, and 6 (33%) had initially been misdiagnosed with hyperekplexia. Multifocal seizures were observed at a median age of 14 days (range: 1-29). During the first months of life, all infants developed progressive encephalopathy, acquired microcephaly, prolonged bouts of apnea, and bradycardia, leading to cardiac arrest and death at a median age of 3.5 months (range: 20 days to 30 months). Only 7 infants (37%) received a definite diagnosis before death, at a median age of 34 days (range: 25-126), and almost two-thirds (12/19, 63%) were diagnosed 8 days to 12 years postmortem (median: 6.5 years). Neuropathology examination, performed in 3 patients, revealed severely delayed myelination and diffuse astrogliosis, sparing the upper cortical layers.DiscussionBRAT1 encephalopathy is a neonatal-onset, rapidly progressive neurologic disorder. Neonates are often misdiagnosed as having hyperekplexia, and many die undiagnosed. The key phenotypic features are multifocal myoclonus, an organized EEG, progressive, persistent, and diffuse hypertonia, and an evolution into refractory multifocal seizures, prolonged bouts of apnea, bradycardia, and early death. Early recognition of BRAT1 encephalopathy allows for prompt workup, appropriate management, and genetic counseling.

Abstract Proprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.

Background and purposeKetogenic diet (KD) is an emerging treatment option for super-refractory status epilepticus (SRSE). We evaluated the effectiveness of KD in patients presenting SRSE including NORSE (and its subcategory FIRES).MethodsA retrospective review of the medical records was performed at the Necker Enfants Malades Hospital. All children with SRSE in whom KD was started during the last 10 years were included. A systematic search was carried out for all study designs, including at least one patient of any age with SRSE in whom KD was started. The primary outcome was the responder rate and Kaplan–Meier survival curves were generated for the time-to-KD response. As secondary outcomes, Cox proportional hazard models were created to assess the impact of NORSE-related factors on KD efficacy.ResultsSixteen children received KD for treatment of SRSE, and three had NORSE presentation (one infectious etiology, two FIRES). In medical literature, 1,613 records were initially identified, and 75 were selected for review. We selected 276 patients receiving KD during SRSE. The most common etiology of SRSE was acute symptomatic (21.3%), among these patients, 67.7% presented with NORSE of immune and infectious etiologies. Other etiologies were remote symptomatic (6.8%), progressive symptomatic (6.1%), and SE in defined electroclinical syndromes (14.8%), including two patients with genetic etiology and NORSE presentation. The etiology was unknown in 50.7% of the patients presenting with cryptogenic NORSE, of which 102 presented with FIRES. Overall, most patients with NORSE benefit from KD (p < 0.004), but they needed a longer time to achieve RSE resolution after starting KD compared with other non-NORSE SRSE (p = 0.001). The response to KD in the NORSE group with identified etiology compared to the cryptogenic NORSE was significantly higher (p = 0.01), and the time to achieve SE resolution after starting KD was shorter (p = 0.04).ConclusionsThe search for underlying etiology should help to a better-targeted therapy. KD can have good efficacy in NORSE; however, the time to achieve SE resolution seems to be longer in cryptogenic cases. These findings highlight the therapeutic role of KD in NORSE, even though this favorable response needs to be better confirmed in prospective controlled studies.

BackgroundDespite the latest advances in prenatal diagnosis and postnatal embolization procedures, intracranial arteriovenous shunts (AVSs) are still associated with high mortality and morbidity rates. Our aim was to evaluate the presentation and clinical course, the neurodevelopmental outcome, and the genetic findings of neonates with AVSs.MethodsIn this retrospective observational study, medical records of neonates with cerebral AVSs admitted to our hospital from January 2020 to July 2022 were revised. In particular, we evaluated neuroimaging characteristics, endovascular treatment, neurophysiological features, neurodevelopmental outcomes, and genetic findings.ResultsWe described the characteristics of 11 patients with AVSs. Ten infants (90.9%) required embolization during the first three months of life. In 5/9 infants, pathological electroencephalography findings were observed; of them, two patients presented seizures. Eight patients performed Median Nerve Somatosensory Evoked Potentials (MN-SEPs): of them, six had an impaired response. We found normal responses at Visual Evoked Potentials and Brainstem Auditory Evoked Potentials. Eight patients survived (72.7%) and were enrolled in our multidisciplinary follow-up program. Of them, 7/8 completed the Bayley-III Scales at 6 months of corrected age: none of them had cognitive and language delays; conversely, a patient had a moderate delay on the Motor scale. The remaining survivor patient developed cerebral palsy and could not undergo Bayley-III evaluation because of the severe psychomotor delay. From the genetic point of view, we found a novel pathogenic variant in the NOTCH3 gene and three additional genomic defects of uncertain pathogenicity.ConclusionWe propose SEPs as an ancillary test to discern the most vulnerable infants at the bedside, particularly to identify possible future motor impairment in follow-up. The early identification of a cognitive or motor delay is critical to intervene with personalized rehabilitation treatment and minimize future impairment promptly. Furthermore, the correct interpretation of identified genetic variants could provide useful information, but further studies are needed to investigate the role of these variants in the pathogenesis of AVSs.

Rheumatoid meningitis (RM) is a rare but often aggressive neurological complication of rheumatoid arthritis. The diagnosis of RM, besides the clinical, radiological, and laboratory criteria, usually requires a cerebral biopsy. Based on the two cases presented in this paper, we propose a new laboratory marker. Cerebrospinal fluid and serum anti-cyclic citrullinated peptide (CCP) IgG were measured, and the intrathecal synthesis of anti-CCP antibodies (anti-CCP antibody index) was calculated using the hyperbolic function. The anti-CCP antibody index was positive in both cases at first diagnosis and progressively decreased after treatments. Together with clinical and radiological criteria, the calculation of the anti-CCP intrathecal synthesis, more than the simple measurement of serum or cerebrospinal fluid anti-CCP antibody titers, may represent a useful tool for RM diagnosis and, possibly, for treatment response.

Background: Using machine learning to combine wrist accelerometer (ACM) and electrodermal activity (EDA) has been shown effective to detect primarily and secondarily generalized tonic-clonic seizures, here termed as convulsive seizures (CS). A prospective study was conducted for the FDA clearance of an ACM and EDA-based CS-detection device based on a predefined machine learning algorithm. Here we present its performance on pediatric and adult patients in epilepsy monitoring units (EMUs).Methods: Patients diagnosed with epilepsy participated in a prospective multi-center clinical study. Three board-certified neurologists independently labeled CS from video-EEG. The Detection Algorithm was evaluated in terms of Sensitivity and false alarm rate per 24 h-worn (FAR) on all the data and on only periods of rest. Performance were analyzed also applying the Detection Algorithm offline, with a less sensitive but more specific parameters configuration (“Active mode”).Results: Data from 152 patients (429 days) were used for performance evaluation (85 pediatric aged 6–20 years, and 67 adult aged 21–63 years). Thirty-six patients (18 pediatric) experienced a total of 66 CS (35 pediatric). The Sensitivity (corrected for clustered data) was 0.92, with a 95% confidence interval (CI) of [0.85-1.00] for the pediatric population, not significantly different (p > 0.05) from the adult population's Sensitivity (0.94, CI: [0.89–1.00]). The FAR on the pediatric population was 1.26 (CI: [0.87–1.73]), higher (p < 0.001) than in the adult population (0.57, CI: [0.36–0.81]). Using the Active mode, the FAR decreased by 68% while reducing Sensitivity to 0.95 across the population. During rest periods, the FAR's were 0 for all patients, lower than during activity periods (p < 0.001).Conclusions: Performance complies with FDA's requirements of a lower bound of CI for Sensitivity higher than 0.7 and of a FAR lower than 2, for both age groups. The pediatric FAR was higher than the adult FAR, likely due to higher pediatric activity. The high Sensitivity and precision (having no false alarms) during sleep might help mitigate SUDEP risk by summoning caregiver intervention. The Active mode may be advantageous for some patients, reducing the impact of the FAR on daily life. Future work will examine the performance and usability outside of EMUs.

Abstract Adherence to the thinness model, self-acceptance such as self-esteem is psychological dynamics influencing the young age and emerging adulthood of women life. The purpose of this study was to investigate the girls and young women’ ability to deal with the adherence to thinness model according to their self-body management thought daily self-perception of ownhabits and aptitude. We analysed their emotional patterns and body management to elucidate the Italian phenomenon. A cross-sectional study was conducted on 2287 Italian female distribute in range age 15–25 years old and distributed in girl and young women groups. We conducted a Survey study by snowball sampling technique. Our results showed that girls had higher emotional pattern scores when their weight and shape fit the thinness model: skinny girls felt positively about their body even if when they did not take adequate care of it. Italian girls consider the underweight body mass index an adherence model. Findings suggest the urgent need to plan prevention programme to model healthy behaviours about their daily good practice overcoming social and cultural models based on appearance.

Salvator Rosa (Napoli, 1615- Roma 1673) fu pittore e poeta tra i più interessanti del secolo diciassettesimo. Il saggio intende indagare il complesso rapporto artistico e personale che Rosa ebbe con la città di Napoli, in cui era nato e dalla quale era quasi fuggito quando era poco più che un ragazzo. Attraverso una lettura delle principali fonti biobibliografiche a lui contemporanee, di alcune delle sue tele, dei versi delle Satire e di stralci delle lettere che a Napoli dedicherà, s’intende sottolineare che della capitale del Meridione la scrittura e l’arte di Salvator Rosa sono in grado di restituirci un’immagine altra rispetto a quella topica di Napoli gentile, perla luminosa di quella Campania felix che proprio nel Seicento attrae pittori e poeti da ogni parte d’Europa. Nei versi di Rosa, come nella scrittura in prosa, Napoli è, infatti, croce e delizia, prigione da cui fuggire e porto di quell’agognato ritorno che, al di là delle leggendarie asserzioni di alcuni biografi romantici, mai avverrà. Salvator Rosa (Naples, 1615- Rome, 1673) was a painter and poet among the most interesting of the seventeenth century. The essay intends to investigate the complex artistic and personal relationship that Rosa had with the city of Naples, where she was born and from which she had fled when she was little more than a boy. Through a reading of the main biobibliographic sources to him contemporary, some of his canvases, the verses of the Satire and the excerpts of the letters that Naples will dedicate, it is meant to point out that in the capital of the South the writing and art of Salvator Rosa are Able to give us an image other than the topical one of Napoli's kind, bright pearl of the Campania felix that in the seventeenth century attracts painters and poets from all over Europe. In the lines of Rosa, as in prose writing, Naples is, in fact, a cross and delight, a prison from which to flee and bring about that auspicious return that, beyond the legendary assertions of some romantic biographers, will never happen.

It has been an honor for us to receive a comment on our article “Fatal Status Epilepticus in Dravet Syndrome” [...]

La Cleopatra di Giovan Battista Giraldi Cinthio fu composta su richiesta del duca Ercole II, nonostante le reticenze del tragediografo, che nell’Apologia della Didone (1541) esplicitava le sue difficoltà a comporre ed allestire una tragedia di argomento storico. Giraldi aveva, infatti, scritto tragedie d’invenzione, ispirate alle novelle dei suoi Ecatommiti e la Didone, di evidente ispirazione virgiliana. Per questo la Cleopatra è una tragedia singolare, che propone, tra l’altro, un’immagine della regina d’Egitto per nulla scontata, nella letteratura come nell’iconografia contemporanea. Il saggio indaga la Cleopatra del Giraldi, accostandola alle varie raffigurazioni pittoriche che sessant’anni più tardi saranno proposte dalla “pittora” italiana Artemisia Gentileschi. The Cleopatra by Giovan Battista Giraldi Cinthio was made on request of the Duke Ercole II, despite the reluctance of the tragedian, who in the advocacy of Didone (1541) expressed his difficulties in composing and preparing a historical tragedy. Giraldi had, in fact, written fictional tragedies, inspired by the stories of his Ecatommiti and Didone, clearly inspired by Virgil. For this reason, Cleopatra is a singular tragedy, which proposes, among other things, an image of the queen of Egypt not obvious at all, in literature as well as in contemporary iconography. The essay investigates the Cleopatra by Giraldi, comparing it to the various pictorial representations that sixty years later would be proposed by the Italian “pittora” Artemisia Gentileschi.

Abstract Perampanel is among the latest AEDs approved, indicated for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures, in patients aged 12 years and older. This paper summarizes the clinical recommendations on the current role of perampanel in the treatment of pediatric epilepsies and future directions for research. The optimal dosage should be comprised between 4 and 12 mg/day, with 8 mg/day being the most common dosage used. The rate and severity of adverse events, including psychiatric symptoms, can be decreased by starting at low doses, and titrating slowly. Overall, perampanel presents an acceptable risk/benefit ratio, but special caution should be made to the risk of seizure aggravation and behavioral problems. The favorable cognitive profile, the ease of use of the titration scheme and the once-daily formulation offer advantage over other AEDs and make this drug particularly suitable for adolescent population. Perampanel is a welcome addition to the armamentarium of the existing AEDs, as it represents a new approach in the management of epilepsy, with a novel mechanism of action and a potential to have a considerable impact on the treatment of adolescents with epilepsy.

The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that has been utilized as the first line treatment for contrasting intractable epilepsy. It is responsible for the presence of ketone bodies in blood, whose neuroprotective effect has been widely shown in recent years but remains unclear. Since glutathione (GSH) is implicated in oxidation-reduction reactions, our aim was to monitor the effects of KD on GSH brain levels by means of magnetic resonance spectroscopy (MRS). MRS was acquired from 16 KD patients and seven age-matched Healthy Controls (HC). We estimated metabolite concentrations with linear combination model (LCModel), assessing differences between KD and HC with t-test. Pearson was used to investigate GHS correlations with blood serum 3-B-Hydroxybutyrate (3HB) concentrations and with number of weekly epileptic seizures. The results have shown higher levels of brain GSH for KD patients (2.5 ± 0.5 mM) compared to HC (2.0 ± 0.5 mM). Both blood serum 3HB and number of seizures did not correlate with GSH concentration. The present study showed a significant increase in GSH in the brain of epileptic children treated with KD, reproducing for the first time in humans what was previously observed in animal studies. Our results may suggest a pivotal role of GSH in the antioxidant neuroprotective effect of KD in the human brain.

Dravet Syndrome (DS) is burdened by high epilepsy-related premature mortality due to status epilepticus (SE). We surveyed centres within Europe through the Dravet Italia Onlus and EpiCARE network (European Reference Network for Rare and Complex Epilepsies). We collated responses on seven DS SCN1A+ patients who died following refractory SE (mean age 6.9 year, range 1.3–23.4 year); six were on valproate, clobazam, and stiripentol. All patients had previous SE. Fatal SE was always triggered by fever: either respiratory infection or one case of hexavalent vaccination. SE lasted between 80 min and 9 h and all patients received IV benzodiazepines. Four patients died during or within hours of SE; in three patients, SE was followed by coma with death occurring after 13–60 days. Our survey supports the hypothesis that unresponsive fever is a core characteristic feature of acute encephalopathy. We highlight the need for management protocols for prolonged seizures and SE in DS.

The aim of this review is to summarize that most relevant technologies used to evaluate gait features and the associated algorithms that have shown promise to aid diagnosis and symptom monitoring in Parkinson’s disease (PD) patients. We searched PubMed for studies published between 1 January 2005, and 30 August 2019 on gait analysis in PD. We selected studies that have either used technologies to distinguish PD patients from healthy subjects or stratified PD patients according to motor status or disease stages. Only those studies that reported at least 80% sensitivity and specificity were included. Gait analysis algorithms used for diagnosis showed a balanced accuracy range of 83.5–100%, sensitivity of 83.3–100% and specificity of 82–100%. For motor status discrimination the gait analysis algorithms showed a balanced accuracy range of 90.8–100%, sensitivity of 92.5–100% and specificity of 88–100%. Despite a large number of studies on the topic of objective gait analysis in PD, only a limited number of studies reported algorithms that were accurate enough deemed to be useful for diagnosis and symptoms monitoring. In addition, none of the reported algorithms and technologies has been validated in large scale, independent studies.

The creation of new blood vessels from existing ones, which is a mechanism called “angiogenesis”, is essential in cancer to supply cancerous growth. Moreover, the development and the progression of the tumor and its metastases are the result of an efficient vascular response. Cancer cells release and activate different angiogenic growth factors and their receptors in the tumor microenvironment to promote the angiogenic process. The most important pro-angiogenic factor is the “Vascular Endothelial Growth Factor” (VEGF) because of its mitogen activity on vascular endothelium. Bevacizumab is a monoclonal antibody that obstructs the binding of circulating vascular endothelial growth factor to its receptors and has been approved for the treatment of primary and recurrent ovarian cancer but also for many other solid tumors.

Obesity is associated with increased risk of cardiometabolic diseases. Adipocytokines (e.g. leptin), produced by the endocrine function of adipose tissue, can contribute to cardiometabolic risk in overweight and obese people. Oxidative stress, imbalance between oxidants and antioxidants, is considered a cardiovascular risk factor. High serum oxidized LDL (oxLDL) levels, marker of lipid peroxidation, a primary cause of atherosclerosis, can contribute to its progression. The aims of this study are to assess markers of oxidative status and cytokine profile and evaluate their role as cardiometabolic risk factors and possible correlations. In this cross-sectional study, we enrolled 76 occupational overweight-obese adults (46 females, 30 males; aged 46.8±9.5; BMI 33.7±4.8 kg/m 2 ) without any previous cardiovascular disease. Oxidative status was measured by evaluating serum Reactive Oxygen Species (ROS) levels, Total Antioxidant Capacity (TAC) and oxLDL concentrations. All subjects' soluble cytokine and adhesion molecule levels were evaluated by cytofluorimetric method and compared with 35 controls matched for sex and age. ROS and oxLDL levels were high in 84% and 92% of the study population, respectively, despite adequate TAC (68%). Female ROS levels were significantly higher than those of males (414±99.3 vs 318±48.2 UCarr, p

The process of tertiarisation of our economies is taking place along with the ever-increasing pervasiveness of information and communication technologies (ICTs). ICTs, in turn, are becoming "convergent" as they share a common basis, namely digital technology. This common basis is becoming so important that it has engendered the need to add a new dimension to the original Smithian idea of the division of labour, i.e. we have to take into account the new forms of the digital division of labour. This work therefore considers the broad process of structural economic dynamics which is engendered by the processes of digitization of our economies, taking the 1960s as a starting point. JEL Codes: O33, L86, L80 Keywords: Technology, Technologies

Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms. The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account. The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far. • A fast GPU based MC has been developed for IOeRT breast treatment planning. • The input is an ultrasound image with defined PTV and OARs. • Different applicator positions, dimensions and angles and beam energies are tested. • Plan is optimised using absorbed dose maps and related DVHs. • Results in the context of conventional and FLASH irradiations are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Epilepsy is a main manifestation in the autosomal dominant mental retardation syndrome caused by heterozygous variants in MEF2C. We aimed to delineate the electro-clinical features and refine the genotype-phenotype correlations in patients with MEF2C haploinsufficiency.Methods: We thoroughly investigated 25 patients with genetically confirmed MEF2C-syndrome across 12 different European Genetics and Epilepsy Centers, focusing on the epileptic phenotype. Clinical features (seizure types, onset, evolution, and response to therapy), EEG recordings during waking/sleep, and neuroimaging findings were analyzed. We also performed a detailed literature review using the terms "MEF2C", "seizures", and "epilepsy".Results: Epilepsy was diagnosed in 19 out of 25 (~80%) subjects, with age at onset <30 months. Ten individuals (40%) presented with febrile seizures and myoclonic seizures occurred in ~50% of patients. Epileptiform abnormalities were observed in 20/25 patients (80%) and hypoplasia/partial agenesis of the corpus callosum was detected in 12/25 patients (~50%). Nine patients harbored a 5q14.3 deletion encompassing MEF2C and at least one other gene. In 7 out of 10 patients with myoclonic seizures, MIR9-2 and LINC00461 were also deleted, whereas ADGRV1 was involved in 3/4 patients with spasms.Conclusion: The epileptic phenotype of MEF2C-syndrome is variable. Febrile and myoclonic seizures are the most frequent, usually associated with a slowing of the background activity and irregular diffuse discharges of frontally dominant, symmetric or asymmetric, slow theta waves with interposed spike-and-waves complexes. The haploinsufficiency of ADGRV1, MIR9-2, and LINC00461 likely contributes to myoclonic seizures and spasms in patients with MEF2C syndrome. [ABSTRACT FROM AUTHOR]

We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis. Postnatal MRI confirmed the prenatal findings. On day 6 the baby presented a focal status epilepticus, partially controlled by phenobarbital, phenytoin, and levetiracetam. After three weeks a moderate improvement in seizure control has been achieved with carbamazepine. Exome sequencing detected a de novo heterozygous mutation in the SCN2A gene, encoding the α II -subunit of a sodium channel. The patient findings expand the phenotype spectrum of SCN2A mutations to epileptic encephalopathies with macroscopic brain developmental features. [ABSTRACT FROM AUTHOR]