Search

Introduction: GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. Methods: Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. Results and discussion: We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in a rare neurological pediatric disease. [ABSTRACT FROM AUTHOR]

The optimal therapeutic management of cyclic vomiting syndrome (CVS) remains elusive. The objective of this study was to document our clinical experience in the Pediatric Department of San Marco Hospital and to survey the literature on pediatric CVS treatment, aiming to update the guidance on the most effective treatment strategies for this not‐so‐uncommon condition. Data from 70 patients with CVS, admitted to our Pediatric Department between September 2011 and December 2021, were aggregated and included in the study. A systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) tool and the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR‐2) method. Treatment responses, as observed both in the literature and in our own experience, are variable. In our cohort, topiramate demonstrated superiority over other pharmacological treatments, exhibiting an efficacy of 85% in the patients treated. A universally accepted treatment protocol for pediatric CVS has yet to be established. The efficacy of first‐line treatments is generally suboptimal, suggesting that topiramate might serve as a safe and effective primary therapeutic option for pediatric CVS. [ABSTRACT FROM AUTHOR]

Background For patients with pharmacoresistant epilepsy, a therapeutic option is ketogenic diet. Currently, data on young infants are scarce, particularly during hospitalization in the neonatal intensive care unit (NICU). Objective The aim of the present study was to evaluate the short-term (3-month) efficacy and side effects of ketogenic diet in infants with "drugs-resistant" epilepsy treated during NICU stay. Methods This retrospective study included infants aged under 2 months started on ketogenic diet during NICU hospitalization to treat drug-resistant epilepsy from April 2018 to November 2022. Results Thirteen term-born infants were included, three (23.1%) of whom were excluded because they did not respond to the ketogenic diet. Finally, we included 10 infants. Six (60%) patients took three antiepileptics before starting the ketogenic diet, while four (40%) took more drugs. Diet had a good response in four (40%) patients. In four patients, the ketogenic diet was suspended because of the onset of serious side effects. The emetic levels of sodium, potassium, and chlorine, pH, and onset of diarrhea, constipation, and gastroesophageal reflux showed significant differences. Ketonuria was higher and blood pH lower in the group that took more than three drugs than in the group taking fewer than three drugs. Conclusion The ketogenic diet is efficacious and safe in infants, but the early and aggressive management of adverse reactions is important to improve the safety and effectiveness of the ketogenic treatment. [ABSTRACT FROM AUTHOR]

Background Autosomal dominant mutations of the KCNQ2 gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype. Methods We searched on PubMed using the search terms " KCNQ2 " AND "therapy" and " KCNQ2 " AND "treatment"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies. Results In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%). Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%). Conclusion Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a "benign" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Palliative care is a comprehensive treatment approach that guarantees comfort for pediatric patients and their families from diagnosis to death. The techniques used for neurological patients in the field of palliative care can enhance the quality of care provided to patients with neurological disorders and support their families. Purpose: This study aimed to analyze the palliative care protocols in use in our department, describe the palliative course in the clinical setting, and propose the implementation of hospital palliative care for long-term prognosis of patients with neurological diseases. Methods: This retrospective observational study examined the application of palliative care from birth to early infancy in neurological patients. We studied 34 newborns with diseases affecting the nervous system impairing prognosis. The study was conducted from 2016 to 2020 at the Neonatology Intensive Care Unit and the Pediatric Unit of the San Marco University Hospital in Catania, Sicily, Italy. Results: Despite current legislation in Italy, no palliative care network has been activated to meet the needs of the population. In our center, given the vast number of patients with neurological conditions requiring palliative care, we should activate a straightforward departmental unit for neurologic pediatric palliative care. Conclusion: The establishment of specialized reference centers that manage significant neurological illnesses is due to neuroscience research progress in recent decades. Integration with specialized palliative care is sparse but now seems essential. [ABSTRACT FROM AUTHOR]

Objective Hypoxic–ischemic encephalopathy (HIE) is the second cause of neonatal deaths and one of the main conditions responsible for long-term neurological disability. Contrary to past belief, children with mild HIE can also experience long-term neurological sequelae. The aim of this systematic review is to determine the predictive value of long-term neurological outcome of (electroencephalogram) EEG/amplitude-integrated electroencephalogram (aEEG) in children who complained mild HIE. Study Design From a first search on PubMed, Google Scholar, and clinicalTrials.gov databases, only five articles were considered suitable for this study review. A statistical meta-analysis with the evaluation of odds ratio was performed on three of these studies. Results No correlation was found between the characteristics of the electrical activity of the brain obtained through EEG/aEEG in infants with mild HIE and subsequent neurological involvement. Conclusion EEG/aEEG monitoring in infants with mild HIE cannot be considered a useful tool in predicting their neurodevelopmental outcome, and its use for this purpose is reported as barely reliable. Key Points HIE is responsible for long-term neurological outcome, even in newborns with mild HIE. No correlation was found between EEG/aEEG trace in infants with mild HIE and neurological sequelae. Neurophysiological monitoring, in mild HIE, cannot predic neurodevelopmental outcome. [ABSTRACT FROM AUTHOR]

Herein, authors present a retrospective, multi-center study to determine the number of accesses to Pediatric Emergency Unit (PEU) of patients within 28 days of life, admitted to (1) the Acute and Emergency Pediatric Unit, San Marco University Hospital, Catania, Italy; (2) Garibaldi Hospital for Emergency Care, Catania, Italy; (3) Cannizzaro Hospital for Emergency Care, Catania, Italy. We included neonates admitted for neurologic problems, from January 2015 to December 2020, to the 1—Acute and Emergency Access of the San Marco University Hospital, Catania, Italy [observation center 1 (OC1)]; 2—Garibaldi Hospital for Emergency Care, Catania, Italy (Observation Center 2—OC2); 3—Cannizzaro Hospital for Emergency Care, Catania, Italy (Observation Center 3—OC3). For each patient, we evaluated the severity of urgency, by studying the admission triage-coloured codes, the clinical data at admission and the discharge diagnosis. Neonates who had access to PEU were 812 in the OC1, 3720 in the OC2, and 748 in the OC3 respectively; 69 (8.4%), 138 (3.7%), and 55 (7.4%) was the proportion of neonatal accesses for neurological conditions. We observed that in the study period, the three hospitals had an important decrease of pediatric accesses to their PEU, but the proportion of neonates who had access to the OC1 for neurologic diseases, with respect to the total neonatal accesses, remained stable. We found that the most frequent neurologic disease for which newborns had access to PEU was Cyanosis, (46.1% of all neonatal accesses). Apnea was the second most frequent cause, with a number of 76 accesses (29%). In the literature there are numerous studies on the assessment of diseases that most frequently concern the pediatric patient in an emergency room, but there are very few references on neonatal accesses for urgent neurologic diseases. Therefore, appropriate training is required to avoid unnecessary tests without overlooking potentially serious conditions. [ABSTRACT FROM AUTHOR]

Background: Ophthalmoplegic migraine, renamed "Recurrent Painful Ophthalmoplegic Neuropathy" (RPON) in 2013 by the International Headache Society is a rare neurologic disorder characterized by recurrent attacks of ophthalmoplegia associated to ipsilateral headache. The etiology is still unknown. Typical magnetic resonance imaging findings show a focal nerve thickening and contrast enhancement. In the majority of cases, there is a full recovery within days or weeks. There is no evidence supporting a specific treatment. The review defines the characteristics of the recurrent painful ophthalmoplegic neuropathy in patients within 2 years of age underlying the importance of the role of magnetic resonance imaging even in presence of the first attack. Thus, an emblematic case report is presented. Case presentation: The authors present a case of third cranial nerve paresis in a 17-month-old male child, presenting a neuroradiological pattern highly suggestive of schwannoma, aneurism or recurrent painful ophthalmoplegic neuropathy. Thus, a review of the literature with the pediatric casuistry of recurrent painful ophthalmoplegic neuropathy occurred within 2 years of age focusing on diagnostic considerations is presented. The authors highlight the importance to consider recurrent painful ophthalmoplegic neuropathy in presence of magnetic resonance imaging findings and clinical symptoms referable to aneurysm or schwannoma. Thus, the review defines the characteristics and the neuroradiological findings at the first RPON attack occurred under 2 years of age. Conclusion: Although two attacks are necessary, the review strongly suggests to consider recurrent painful ophthalmoplegic neuropathy even at the first attack, in presence of described characteristics and the aforementioned magnetic resonance imaging findings. [ABSTRACT FROM AUTHOR]

Background: The study of consciousness has always been considered a challenge for neonatologists, even more when considering the uterine period. Our review aimed to individuate at what gestational age the fetus, which later became a premature infant, can feel the perception of external stimuli. Therefore, the aim of our review was to study the onset of consciousness during the fetal life. Materials and methods: A literature search was performed in Medline-PubMed database. We included all papers found with the following MeSH words: "consciousness or cognition or awareness or comprehension or cognitive or consciousness of pain" in combination with "embryo or fetus or fetal life or newborn." Studies were selected if titles and/or abstracts suggested an association between formation of consciousness (the basics of neurodevelopment) and preterm infant or fetus. Titles and abstracts were first screened by three independent reviewers according to Cochrane Collaboration's recommendations. Results: From the literature review, we found only 8 papers describing the onset of consciousness in the transition period from fetus to premature newborn. Therefore, according to these papers, we temporally analyzed the formation of the thalamocortical connections that are the basis of consciousness. Conclusions: We can conclude that from a neuroanatomical point of view, it is rather unlikely that the infant can be seen as a conscious human before 24 weeks of gestational age, thus before all the thalamocortical connections are established. Further literature data have to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Aim: Amplitude‐integrated electroencephalography (aEEG)'s accuracy compared to conventional electroencephalography (cEEG) has not been fully established. The aim of our study was to conduct a systematic review on the sensitivity of the aEEG for neonatal seizure detection. Methods: Studies from PubMed and Google Scholar databases comparing recordings of cEEG and aEEG in newborns were included according to the PRISMA method. A quality assessment using the QUADAS‐2 tool was provided. A random‐effect model was used to account for different sources of variations among studies. Publication biases were represented by a funnel plot, and funnel plot symmetry was assessed. Results: Fourteen studies were reported; sensitivity of each diagnostic tool used (single‐channel aEEG, two‐channel aEEG, two‐channel aEEG plus raw trace EEG) was compared to that of the gold‐standard cEEG and to those of the other methods used. Overall sensitivity of the aEEG ranged from 31.25% to 90%. Conclusion: Our study provides evidence that sensitivity of aEEG varies significantly and that seizure detection rate is lower than that of cEEG. The two‐channel aEEG with raw trace EEG shows a high sensitivity and might represent a valid alternative to the cEEG in the setting of neonatal intensive care units (NICUs). [ABSTRACT FROM AUTHOR]

Although rare, ischemic lesions in neonates may occur in Neonatal Intensive Care Units (NICUs) secondary to routine procedures and/or medicaments. We present double‐center case series, reporting three preterm neonates with ischemic lesions following cardiac arrest and radial blood sampling. The overall outcome after treatment with 2% nitroglycerine (NTG) ointment showed optimal results with no adverse events. The most frequent causes responsible for the onset of such lesions are peripheral arterial catheterization procedures and dopamine extravasation. Our series describe the cardiac arrest as an underestimated cause of onset. Despite the optimal results emerging from the treatment of such lesions with NTG ointment, both in our experience and in the scientific literature, a defined protocol for its use in NICUs is not currently available, hence the need for further studies. [ABSTRACT FROM AUTHOR]

Precision medicine (PM) in epilepsy is an emerging field that aims to customize medical treatment based on individual patient characteristics. It involves a multidisciplinary approach that incorporates genetics, environmental factors, and lifestyle information. While PM and personalized medicine are often used interchangeably, there are nuanced distinctions between the two. The article "Steps to Improve Precision Medicine in Epilepsy" focuses on the technological and methodological advancements in PM for epilepsy, but does not delve into the historical treatment advancements or the pathophysiological evolution of epilepsy syndromes. The authors argue that true precision therapy involves tailoring treatments based on a comprehensive individual biological profile, starting from genetic mutations and including other omics sciences. They suggest that the current application of PM in epilepsy falls within a stratified medicine approach, where patients are segmented into subpopulations with distinct susceptibilities or responses to treatment. The article concludes that the landscape of epilepsy treatment is dynamic and involves a balance between precise targeting and individual care. [Extracted from the article]

Background: Pediatric cyclic vomiting syndrome (CVS) is a little‐known clinical condition, frequently diagnosed with delay. This study aims to describe the clinical presentation and management and to define possible predictive factors of the disease outcome. Methods: In this retrospective study, all children who were diagnosed with CVS during the period 2010–2019 in three tertiary academic centers were included. The association between clinical variables and outcomes was investigated. Key Results: Fifty‐seven children were included (male/female ratio 1.3:1; mean age at diagnosis 8.2 years). At the time of diagnosis, 63% of children had at least one episode every month. One or more prodromes were reported by 75% of patients. Family history of migraine was reported for 47% of children. Nearly, all of the children were started on prophylactic treatment. The median follow‐up period was 29 months ± 15. Overall, 56% of children had resolution of vomiting. Twenty‐six percent of children developed migraine. There were no differences in gender, age at onset, duration of follow‐up, severity, medication, family history, or trigger factors between children who underwent resolution of vomiting and those who did not, or between children who suffered from migraine or not at follow‐up. Four types of disease outcome were recognized, that is, resolution of vomiting with or without associated symptoms; persistence of vomiting with or without associated symptoms. Conclusions and Inferences: Cyclic vomiting syndrome clinical presentation has inter‐individual variability. Most children recover at follow‐up, but often develop further somatic symptoms. In this study, no clinical variable clearly predicted the evolution of the syndrome toward one or the other outcome. [ABSTRACT FROM AUTHOR]

Neonatal seizures (NS) occur in the first 28 days of life; they represent an important emergency that requires a rapid diagnostic work-up to start a prompt therapy. The most common causes of NS include: intraventricular haemorrhage, hypoxic-ischemic encephalopathy, hypoglycemia, electrolyte imbalance, neonatal stroke or central nervous system infection. Nevertheless, an Inborn Error of Metabolism (IEM) should be suspected in case of NS especially if these are resistant to common antiseizure drugs (ASDs) and with metabolic decompensation. Nowadays, Expanded Newborn Screening (ENS) has changed the natural history of some IEMs allowing a rapid diagnosis and a prompt onset of specific therapy; nevertheless, not all IEMs are detected by such screening (e.g. Molybdenum-Cofactor Deficiency, Hypophosphatasia, GLUT1-Deficiency Syndrome) and for this reason neonatologists have to screen for these diseases in the diagnostic work-up of NS. For IEMs, there are not specific semiology of seizures and EEG patterns. Herein, we report a systematic review on those IEMs that lead to NS and epilepsy in the neonatal period, studying only those IEMs not included in the ENS with tandem mass, suggesting clinical, biochemical features, and diagnostic work-up. Remarkably, we have observed a worse neurological outcome in infants undergoing only a treatment with common AED for their seizures, in comparison to those primarily treated with specific anti-convulsant treatment for the underlying metabolic disease (e.g.Ketogenic Diet, B6 vitamin). For this reason, we underline the importance of an early diagnosis in order to promptly intervene with a targeted treatment without waiting for drug resistance to arise. [ABSTRACT FROM AUTHOR]

In these last 25 years, the Neonatal Emergency Transport (NET) service has been widely improved in Italy. To date, all National areas are covered by a NET service; 53 NET centers have been activated in all the Italian territory. Herein, the authors present an observational study to evaluate the rate of infantile mortality after introduction of NET in Sicily, and to study the efficiency of this service in reducing these rates of mortality in vulnerable neonates, transported from primary care birth centers to tertiary facilities to undergo to specialized NICU assistance. All neonates who required an emergency transport by NETS were included. No exclusions criteria were applied. Demographic and regional infantile mortality data, expressed as infant mortality rate, were selected by the official government database (ISTAT- National Statistic Institute—http://www.istat.it). All data were respectively divided into three groups: data concerning transport, clinical condition, and mortality of the transported patients. We transported by NET 325 neonates. The analysis of the infant mortality rate (per 1.000 live births) in Catania from 2016 to 2018 was reduced compared to the same rate calculated before NETS activation (4.41 index before 2016 vs 4.17 index after 2016). These data showed an increase in other provinces (Enna, Caltanissetta, and Agrigento). 61% of neonates showed a respiratory disease. During the study period the proportion of neonates with a Mortality Index for Neonatal Transportation—MINT < 6 has been reduced, while there was an increase of neonates with higher Transport Risk Index of Physiologic Stability-TRIPS score results. The slight decrease of infantile mortality in Catania during the first three years after introduction of NET follows the same trend of all Italian territories, showing the importance of this service in reducing infantile mortality. [ABSTRACT FROM AUTHOR]

Objective  The new coronavirus infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized as a global public health emergency, and neonates may be more vulnerable due to their immature immune system. The first aim of this study was to report our experience on the management of neonates from mothers with SARS-CoV-2 infection focusing on a 28-day follow-up since birth. The second aim is to assess how many data on neonatal outcomes of the first month of life are reported in literature, performing a systematic review and meta-analysis. Study design  We report our experience based on routine management of neonates born to mothers with SARS-CoV-2 infection and follow-up until 28 days of life. Results  In our experience at discharge, 1/48 (2.08%) of entrusted (mother refusing personal protective equipment) and none of separated presented positive nasopharyngeal swab (p  = NS). All babies show good outcome at 28 days of life. The literature data show that the percentage of positive separated infants is significantly higher than the percentage of infants entrusted to positive mothers with appropriate control measures (13.63 vs. 2.4%; p  = 0.0017). Meta-analysis of studies focused on follow-up showed a 2.94% higher risk of incidence of SARS-CoV-2 infection in entrusted newborns than in separated newborns (95% confidence interval: 0.39–22.25), but this was not significant (p  = 0.30). Conclusion  A vertical transmission in utero cannot be totally excluded. Since in newborns, the disease is often ambiguous with mild or absent symptoms, it is important to define the most efficient joint management for infants born to COVID-19 positive mothers, being aware that the risk of horizontal transmission from a positive mother, when protective measures are applied, does not seem to increase the risk of infection or to affect the development of newborns from birth to first four weeks of life, and encourages the benefits of breastfeeding and skin-to-skin practice. Key Points Entrusting the newborn to the positive mother does not increase the risk of infection. Our follow-up shows that newborns have good growth and outcome at one month of life. Applying protective measures we suggest breastfeeding and skin-to-skin practice. [ABSTRACT FROM AUTHOR]

Background: Neonatal brain injury (NBI) can lead to a significant neurological disability or even death. After decades of intense efforts to improve neonatal intensive care and survival of critically ill newborns, the focus today is an improved long-term neurological outcome through brain-focused care. The goal of neuroprotection in the neonatal intensive care unit (NICU) is the prevention of new or worsening NBI in premature and term newborns. As a result, the neonatal neurocritical care unit (NNCU) has been emerging as a model of care to decrease NBI and improve the long-term neurodevelopment in critically ill neonates.Purpose: Neurocritical care (NCC) Sicilian project includes three academic sites with NICU in Sicily (Catania, Messina, and Palermo), and its primary goal is to develop neurocritical neonatal care unit (NNCU).Methods: In 2018, the three NICUs created a dedicated space for neonates with primary neurological diagnosis or at risk for neurological injuries-NNCU. Admission criteria for eligible patients and treatment protocols were created. Contact with parents, environmental protection, basic monitoring, brain monitoring, pharmacological therapy, and organization of the staff were protocolized.Results: Evaluation of the efforts to establish NNCU within existing NICU, current protocols, and encountered problems are shown. Implications for Practice. Our outcome confirmed the need for dedicated NNCU for neuroprotection of critically ill neonates at risk for a neurological injury. Although the literature on neonatal neurocritical care is still scarce, we see the value of such targeted approach to newborn brain protection and therefore we will continue developing our NNCU, even though there have been problems encountered. The project of building NNCU will continue to be closely monitored.Conclusions: The development of our neonatal neurocritical model of care is far from being completed. Although it is currently limited to the Sicilian area only, the goal of this paper is to share the development of this multicenter interdisciplinary project focused on a newborn brain protection. After evaluating our outcome, we strongly believe that a combined expertise in neonatal neurology and neonatal critical care can lead to an improved neurodevelopmental outcome for critically ill neonates, from the extremely preterm to those with brain injuries. [ABSTRACT FROM AUTHOR]

Aim: The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic protocols. We systematically reviewed the available literature examining neonatal seizure treatments to clarify which drugs are the most effective for the treatment of specific neurologic disorders in newborns. Method: We reviewed all available, published, literature, identified using PubMed (published between August 1949 and November 2020), that focused on the pharmacological treatment of electroencephalogram (EEG)-confirmed neonatal seizures. Results: Our search identified 427 articles, of which 67 were included in this review. Current knowledge allowed us to highlight the good clinical and electrographic responses of genetic early-onset epilepsies to sodium channel blockers and the overall good response to levetiracetam, whose administration has also been demonstrated to be safe in both full-term and preterm newborns. Interpretation: Our work contributes by confirming the limited availability of evidence that can be used to guide the use of anticonvulsants to treat newborns in clinical practice and examining the efficacy and potentially harmful side effects of currently available drugs when used to treat the developing newborn brain; therefore, our work might also serve as a clinical reference for future studies. [ABSTRACT FROM AUTHOR]

Background: Ocular paroxysmal events can accompany a variety of neurological disorders. Particularly in infants, ocular paroxysmal events often represent a diagnostic challenge. Distinguishing between epileptic and nonepileptic events or between physiological and pathologic paroxysmal events can be challenging at this age because the clinical evaluation and physical examination are often limited. Continuous polygraphic video-electroencephalography (EEG) monitoring can be helpful in these situations.Methods: We review ocular paroxysmal events in newborns and infants. The aim is to improve clinical recognition of ocular paroxysmal events and provide a guide to further management. Using the PubMed database, we identified studies focused on all ocular motor paroxysmal events in neonates and infants.Results: Fifty-eight articles were selected on the topic. We summarized and divided these studies into those describing nonepileptic and epileptic ocular paroxysmal events.Conclusions: The diagnosis of ocular paroxysmal events can be difficult, but their recognition is important because of the variety of underlying etiologies. The distinction between epileptic versus nonepileptic ocular paroxysmal events often often requires polygraphic video-EEG to identify the epileptic events. For nonepileptic events, further testing can characterize pathologic ocular movements. To determine the etiology and prognosis of ocular paroxysmal events, a multimodal approach is required, including a thorough full history and clinical examination, polygraphic video-EEG monitoring, neuroimaging, and a careful follow-up plan. [ABSTRACT FROM AUTHOR]

Amniotic band syndrome (ABS) is a set of congenital malformations that mainly affect the limbs and more rarely the skull, face, chest, and abdomen. Two main hypotheses have been proposed to explain the nature of the disorder: an intrinsic and extrinsic factor. We report a newborn with ABS presenting with several malformations involving both hands and foot. In this case, the malformative event localized at the hands and right foot without involvement of any other internal organs and is asymmetric which leads us to suppose the extrinsic factor as cause of the ABS. [ABSTRACT FROM AUTHOR]

The aim of this paper is to describe an uncommon physiological EEG artifact in newborns caused by tongue movements (TM), mimicking anterior slow dysrhythmia (ASD). The subjects are two full-term newborns (39 weeks gestational age (GA)), admitted to the Neonatal Intensive Care Unit for respiratory distress. Both underwent polygraphic video-EEG recording in order to better characterize tremor-like movements of all four limbs that appeared 48 hours after birth. Multichannel video-EEG polygraphy was performed using the 10–20 electrode montage modified for neonates. Ninety minutes of EEG was recorded for each subject, capturing different behavioral states. Background EEG activity was normal for both subjects. During active sleep (AS), synchronous and symmetric slow activity was recorded over bifrontal head regions. For subject 1, bursts of monomorphic 2 Hz delta waves, with an amplitude between 50–100 μV lasting two seconds, were recorded and identified as anterior slow dysrhythmia. For subject 2, polymorphic 1-2 Hz delta waves, 50–100 μV in amplitude and lasting for 20 seconds, were recorded only during suction. After thorough analysis of simultaneous digital video recording synchronized with the EEG trace, this activity was thought to be compatible with glossokinetic artifact. Interpretation of neonatal EEG can be challenging; the background activity is frequently intermixed with physiological artifacts, such as ocular, muscle and movement artifacts, complicating the interpretation. Even continuous video-recording might not make the diagnosis immediately obvious. Therefore, when a rhythmic monomorphic pattern without evolution in amplitude or frequency is seen, we suggest that tongue movement artifact should be considered. [ABSTRACT FROM AUTHOR]

Background. Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates. Objectives. The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures. Method. This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele," Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1). Results. We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB. Conclusion. This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age group. [ABSTRACT FROM AUTHOR]

Background: Grisel's syndrome is a non-traumatic subluxation of the atlantoaxial joints, which is caused by an inflammatory process involving the upper neck. Torticollis, neck pain, and reduced neck mobility are the main clinical signs of presentation. Predisposing factors are trauma, hyperlaxity of the transverse and alar ligaments of the atlantoaxial joints, and surgical interventions carried out in this area. Several viral and bacterial pathogens have been reported as causative events of Grisel's syndrome, including Epstein-Barr virus, Kawasaki disease, Streptococcus pyogenes, Staphylococcus aureus, and other infectious agents. Grisel's syndrome linked to Mycoplasma pneumoniae infection as the trigger has not previously been reported. Mycoplasma pneumoniae is a small prokaryotic microbe and a frequent etiologic factor of respiratory tract infections and, less frequently, of extrapulmonary body organs. The recognition of the Grisel's syndrome is based on clinical and neuroradiological investigations, and early diagnosis and specific treatment are crucial to the successful outcome of the disease.Results: We report the case of an 8-year-old girl with Grisel's syndrome caused by an upper respiratory tract infection due to Mycoplasma pneumoniae. Diagnostic suspicion and treatment of Grisel's syndrome were established quickly by anamnestic and clinical data and confirmed by radiological findings. The girl was immediately treated with specific antibiotic therapy and cervical immobilization, thus preventing the most dangerous complications of the disorder.Conclusion: Mycoplasma pneumoniae, among the other infectious agents, may be cause of scute torticollis and Gresel's syndrome. [ABSTRACT FROM AUTHOR]

Abstract Array-based comparative genomic hybridization is a routine technology that helps clinicians in the diagnostic evaluation of individuals presenting with developmental delay or malformation anomalies. With this technique, several patients affected by microdeletion 2p15-p16.1 have been reported and this anomaly has been recognized as a distinct syndrome. In contrast, clinical features of patients with microduplication in the same region have been registered mainly in clinical and genetic data-bases and to date just a single patient has been reported in detail in the literature. A 12-year-old boy with 2p15-p16.1 microduplication presented with moderate neurodevelopment delay, epileptic seizures, behavioral disturbances, and minor dysmorphic features. The role of 2p15-p16.1 duplication in this case, and the others published in data-bases with a similar molecular duplication, are discussed. [ABSTRACT FROM AUTHOR]

Background: This study aimed to show the impairment of autonomic cardiac conduction causing bradycardia and/or electrocardiographic alterations in children affected by spinal muscular atrophy type 1 and 2 (SMA 1 and 2). Methods: We included 25 spinal muscular atrophy patients, admitted from November 2016 to May 2017. All patients underwent an electrocardiographic examination and we studied PR and QRS intervals, P-waves and QRS amplitudes, and heart rate in spinal muscular atrophy patients compared to a control group. Results: In all patients, we found longer PRi and QRSi (P < .05), lower P-wave and QRS complex amplitudes (P < .01), and a decreased heart rate (P < .01) with respect to controls. When we divided our patients into SMA1 and SMA2 subgroups, we found that statistical differences were maintained for P-wave and QRS complex amplitudes and heart rate, but not for PRi and QRSi with respect to controls. Conclusion: We suggest the hypothesis of SMN expression on cardiac tissue condition and/or autonomic cardiac conduction. [ABSTRACT FROM AUTHOR]

The aim of our study was to describe the clinical, electroencephalogram, molecular findings and the diagnostic and therapeutic flow-chart of children with pyridoxine-dependent epilepsies (PDEs). We performed a retrospective observational study on children with PDEs, diagnosed and followed-up in Italian Pediatric Departments. In each centre, the authors collected data from a cohort of children admitted for intractable seizures, responsive to pyridoxine administration and resistant to other anticonvulsant therapies. Data were retrospectively analysed from January 2016 to January 2017. Sixteen patients (13 males, and 3 females) were included. We found that 93.75% of patients underwent conventional anticonvulsant therapy before starting pyridoxine administration and 62.5% had ex-juvantibus diagnosis, as specific serum diagnostic tests had been performed in only 37.5% of patients by alpha-AASA and pipecolic acid blood and urine dosage. The most common type of seizure was generalized tonic-clonic in 7 patients and the most common EEG pattern was characterized by a 'burst suppression' pattern. Before pyridoxine administration, other anticonvulsant drugs were used in 93.75% of patients, with consequent onset of drug-resistance. Phenobarbital was the most frequently used drug as first-line treatment. The importance of our study relies on the need of a deeper knowledge of PDEs in terms of early diagnosis, avoiding incorrect treatment and related adverse events, clinical and EEG pathognomonic features, and genetic aspects of the disease. [ABSTRACT FROM AUTHOR]

Background: Woolly Hair is an uncommon congenital anomaly of the scalp hair presenting with strongly coiled hair involving a localized area of the scalp or covering the entire side and occurring in non-black people. Isolated or localized wooly hair is usually benign and is not related to other disorders and/or complications. On the contrary, the generalized type may be related to disorders and syndromes affecting heart, cutis, liver and gastrointestinal organs. Among the syndromes presenting with wooly hair, the most known are the Naxos syndrome, the Carvajal- Huerta syndrome, the wooly hair/hypotrichosis, the ectodermal dysplasia-skin fragility, the tricho-hepato-enteric syndrome. Case presentation: To our knowledge, no cases of wooly hair syndromes has been associated to neurologic involvement. Among the clinical notes of patients admitted in the Pediatric Units of the Catania University, we have selected four individuals presenting wooly hair, who showed different clinical features and course: case 1 presenting with a localized wooly hair type; case 2, member of a family affected by WH with autosomal dominant inheritance, not associated to complications; case 3, a wooly hair patient who displayed a progressive, severe form of Rasmussen's encephalitis with fatal evolution, and case 4, wooly hair associated to brain malformation and drug-resistant epilepsy. Conclusions: With this report, we aim to underline the wide spectrum of clinical presentation of individuals with WH and in particular we wish to give an annotation on a possible association of WH with severe neurologic disorders. [ABSTRACT FROM AUTHOR]

Congenital muscular dystrophies (CMDs) are a wide group of muscular disorders that manifest with very early onset of muscular weakness, sometime associated to severe brain involvement. The histologic pattern of muscle anomalies is typical of dystrophic lesions but quite variable depending on the different stages and on the severity of the disorder. Recent classification of CMDs have been reported most of which based on the combination of clinical, biochemical, molecular and genetic findings, but genotype/phenotype correlation are in constant progression due to more diffuse utilization of the molecular analysis. In this article, the Authors report on CMDs belonging to the group of dystroglycanopathies and in particular on the most severe forms represented by the Fukuyama CMD, Muscle-Eye-Brain disease and Walker Walburg syndrome. Clinical diagnosis of infantile hypotonia is particularly difficult considering the different etiologic factors causing the lesions, the difficulty in localizing the involved CNS area (central vs. peripheral) and the limited role of the diagnostic procedures at this early age. The diagnostic evaluation is not easy mainly in differentiating the various types of CMDs, and represents a challenge for the neonatologists and pediatricians. Suggestions are reported on the way to reach a correct diagnosis with the appropriate use of the diagnostic means. [ABSTRACT FROM AUTHOR]

Among autonomic seizures apnea still represent a challenge for physicians, and it might constitute the only isolated sign of neurological disorder. The aim of this review is to describe ictal apnea (IA) and its treatment options. MeSH and keywords were combined: "neonatal seizures", "ictal neonatal apnea", "apneic seizures". All identified papers were screened for neonatal seizures titles and abstracts; case reports describing patients with IA as an isolated manifestation of neonatal seizures were included. Eight studies including a total of 13 patients were identified. Among 13 patients, 9 were full-term and 4 were preterm neonates. All patients developed IA within twenty-one days from birth. Etiologies of seizures included: temporal lobe hemorrhage (3 pt), occipital stroke (1 pt), hypoxic-ischemic encephalopathy (HIE) (1 pt), parasagittal injury (1 pt), 18 trisomy (2 pt). Five patients showed no structural CNS alterations. Ten patients had the ictal focus localized in the temporal lobe; the occipital lobe was the second most involved site. Phenobarbital was administered in 76 % of cases with IA (10 pt), and showed efficacy in 74 % of them; 2 required a second anti-epileptic drug (AED) to reach seizure control. Levetiracetam was given to 11 % (2 pt) successfully. Only one was treated with midazolam and one did not require any anticonvulsant. Not homogeneous data and paucity of isolated IA currently reported in literature limits agreement about definition, management and treatment of entity, however an ever-growing attention is needed, and EEG/aEEG, despite their possible controversies in the diagnosis, should be performed to investigate unexplained forms of apnea. [ABSTRACT FROM AUTHOR]

Congenital melanocytic nevi (CMN) are observed frequently in children. The anomalous skin shows a widely variable clinical expression not only in the anatomic location, but also in color, morphology and superficial structure. According to the width CMN are distinguished in small, medium, large or giant. Aside the cosmetic problem and its psychological implications, CMN may present with severe complications consisting of malignant transformation and/or central nervous system involvement. We report on a 3-month old infant with an extensive CMN in the left leg, which extended from the lower portion of the knee to the foot, with satellite nevi. Concomitant with the extensive nevi in the same district a remarkable reduction in size was present, and involved the adipose and muscle tissues, contributing to a counterpart diameter difference of 5 cm, without bone involvement. Melanocytic nevi and soft tissue undergrowth in the leg is a usual association; a pathogenic explanation on the anomaly involving concomitantly the skin and the underneath soft tissues is advanced. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the sentinel innate immune cells that initiate antigen-specific adaptive immune responses. On the one hand, DCs have been extensively analyzed because of their roles in immune response against pathogens, and on the other hand, there are numerous other studies that have investigated their role in immune tolerance of autoimmune disorders such as type 1 diabetes, systemic lupus erythematosus, multiple sclerosis (MS), and psoriasis. The presence, recruitment, and activation of DCs in the cerebral spinal fluids of experimental allergic encephalomyelitis and MP models, initiated the long array of studies of pathogenic and the potential therapeutic role of DCs in MS. Many classic disease-modifying therapies that are employed have used strategies to alter the maturation and function of DCs; several other novel therapeutic strategies are currently under investigations, which we aim to briefly review in this article. We have focused on reviewing the role of DCs in the central nervous system (CNS), underlying their pathogenesis involvement, and proposing targeting therapies for autoimmune CNS disorders. [ABSTRACT FROM AUTHOR]

Pyridoxine dependent epilepsies (PDEs) are rare autosomal recessive disorders with onset in neonatal period. Seizures are typically not responsive to conventional antiepileptic drugs, but they cease after parental pyridoxine administration. Atypical forms are characterized partly response to pyridoxine and a late onset of symptoms (up to the age of three years). Prevalence is variable and it has rarely been described. The genes involved in PDEs are the gene encoding for the Alpha-aminoadipic-semialdehyde dehydrogenase (ALDH7A1) and PROSC gene, which encodes a pyridoxal-5-phosphate binding protein. Mutations in the gene encoding for the pyridoxal-5'-phosphate oxidase enzyme (PNPO) are responsible of a clinical entity similar to PDEs responsive to pyridoxal-5-phosphate administration not to pyridoxine administration. PDEs diagnosis is often delayed because they are suspected only after conventional anticonvulsant drugs resistance. Herein authors aim to present an expert point of view on PDEs in childhood, reviewing the most recent literature data and proposing a new therapeutical approach for seizures of unknown origin in all those children up to the age of three years. [ABSTRACT FROM AUTHOR]

Summary Background Zoonoses are human infectious diseases caused by pathogens that primarily infect animals. Mediterranean Spotted Fever (MSF) represents one such example, affecting the Mediterranean region, in which household animals can be immune-carriers of infected ticks. Materials and methods We retrospectively analysed the incidence and the clinical and laboratory features of MSF caused by R.Conorii in children admitted to the Paediatric Operative Unit from 1987 to 2010, for persistent fever and generalised macular-popular erythematous lesions. Clinical, immunological and serological parameters of 55 cases of Rickettsia infections observed in children between 2 and 11 years of age were collected. Results We found an increasing incidence of MSF in childhood from 1987 to 2010. Diagnosis of MSF at the moment of hospital admission was done in 16 patients (29.09%). The presence of the typical Tache noire was observed in 16 cases out of 55 patients (29.09% of cases). We noticed a different representation of R. conorii antigens in serological testing over the time period of the study, corresponding to overall higher incidence rates for infection in the latter years. We also observed a higher incidence of infection in those years in which all four antigens were found positive at serum testing with respect to those years in which only two of the four antigens were observed (1987-1990: 0-16%; 2007-2010: 0.46%; P<0.005). Conclusions These changes in R. conorii antigenicity may be the cause of higher pathogenicity in this parasite, perhaps linked to increased immigration along with consequent changes in the epidemiology of infectious diseases in host countries. [ABSTRACT FROM AUTHOR]

Background and objective In the last 20 years, research efforts have been focused on the use of non-invasive ventilation ( NIV) as a mean of avoiding tracheostomy in patients affected by neuromuscular diseases ( NMD). Nocturnal NIV has been a particular focus as sleep is a risk factor for respiratory failure in NMD patients. The objective of our study was to evaluate the efficacy of nocturnal NIV in improving the respiratory function of NMD patients evaluated by polysomnography ( PSG) and arterial blood gas ( ABG) analysis parameters. Methods Ten children affected by NMD underwent PSG and ABG analysis evaluation at the onset of their respiratory failure and during nocturnal NIV therapy. Results We found a statistically significant improvement of the lowest oxygen desaturation (nadir SaO2), apnoea-hypopnoea index ( AHI) and oxygen desaturation index ( ODI) after NIV treatment in all patients. Mean SaO2 also improved, although this result was not statistical significant, while the percentage of episodes of desaturation with a SaO2 <90% and <80% decreased with a statistical significance ( P < 0.0001). After NIV, only one patient showed an episode of desaturation lasting more than 5 min (10.6 min length), and we also found an improvement of daytime blood gas parameters with a normalization of these indexes. Conclusions NIV was effective in improving respiratory parameters at night in patients affected by respiratory muscular weakness, as evaluated by PSG and ABG analysis. [ABSTRACT FROM AUTHOR]

Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis that was chronologically, clinically, and biologically related to a previous Chlamydia pneumoniae infection. On our knowledge, in the literature it is the youngest patient with renal involvement during course of Chlamydia pneumoniae infection ever reported. Conclusions. The present case supports the hypothesis of a rather close causal relationship between this infective agent and renal and glomerular symptoms occurred in this child, during an acute episode of respiratory disease. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is an established, nonpharmacological treatment for drug-resistant epilepsy (DRE). Actually, KD and its variants have been shown to be elective and resolute for patients with glucose transporter type 1 (GLUT1) deficiency. The aim of this review was to study the use of KD and its variants in infancy, including the neonatal age, and demonstrate the safety and efficacy of this treatment in patients with the age of 0–23 months affected by DRE already subjected to pharmacological approach attempts. A literature search was conducted using PubMed as the medical database source. We used the age limit of 0–23 months, and we considered only articles published between the years 2015 and 2018, in light of increasing interest worldwide in the use of KD and its variants to manage DRE. We included 52 publications: 1 Cochrane study, 22 retrospective studies, 9 prospective studies, 4 randomized controlled trials (RCTs), 12 clinical cases, and 4 clinical reviews. Literature data showed that KD and its variants are safe and useful in patients with the age of 0–23 months with DRE. Classical KD is of first choice in the treatment of GLUT1 deficiency. Earlier introduction of KD in GLUT1 promises a better outcome and a decrease in seizure frequency in these patients. • The ketogenic diet is safe and useful in pediatric non-pharmacological treatment for drug-resistant epilepsy. • KD is of first choice in the treatment of Glucose transporter type 1 disorder and Pyruvate Dehydrogenase Complex deficiency. • KD in neonates with drug-resistant epilepsy is useful to perform a prompt diagnosis of Glucose transporter type 1 deficiency. [ABSTRACT FROM AUTHOR]

Abstract: We describe an infant with cutaneous and leptomeningeal diffuse hemangiomata. Clinical facial anomalies were evident at birth. Routine transfontanellar ultrasonography revealed very diffuse leptomeningeal hemangioma. Magnetic resonance imaging during the first days of age confirmed vascular lesions. The patient was otherwise normal, and was monitored at ages 3.5, 9, and 18 months. Rapid resolution of the hemangioma occurred within 1 year. The infant did not present with persistent embryonic arteries, a posterior fossa, or other malformations typically reported in Pascual-Castroviejo type II syndrome. However, the characteristic skin color, leptomeningeal hemangioma, and rapid involution prompted the diagnosis of Pascual-Castroviejo II syndrome in its wider, benign spectrum. [Copyright &y& Elsevier]

Preterm birth (PTB), defined as parturition prior to 37 weeks of gestation, is the leading cause of morbidity and mortality in the neonatal population. The incidence and severity of complications of prematurity increase with decreasing gestational age and birthweight. The aim of this review study is to select the most current evidence on the role of oxidative stress in the onset of preterm complication prevention strategies and treatment options with pre-clinical and clinical trials. We also provide a literature review of primary and secondary studies on the role of oxidative stress in preterm infants and its eventual treatment in prematurity diseases. We conducted a systematic literature search of the Medline (Pubmed), Scholar, and ClinicalTrials.gov databases, retroactively, over a 7-year period. From an initial 777 articles identified, 25 articles were identified that met the inclusion and exclusion criteria. Of these, there were 11 literature reviews: one prospective cohort study, one experimental study, three case-control studies, three pre-clinical trials, and six clinical trials. Several biomarkers were identified as particularly promising, such as the products of the peroxidation of polyunsaturated fatty acids, those of the oxidation of phenylalanine, and the hydroxyl radicals that can attack the DNA chain. Among the most promising drugs, there are those for the prevention of neurological damage, such as melatonin, retinoid lactoferrin, and vitamin E. The microbiome also has an important role in oxidative stress. In conclusion, the most recent studies show that a strong relationship between oxidative stress and prematurity exists and that, unfortunately, there is still little therapeutic evidence reported in the literature. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy type 0 is a severe form of spinal muscular atrophy that is usually fatal in the first months of life. These children present with arthrogryposis multiplex congenita and respiratory compromise. We describe a child with spinal muscular atrophy and arthrogryposis multiplex congenita who has had a much better course and is alive without ventilator support at age 6 years. This case illustrates that the prognosis for spinal muscular atrophy and arthrogryposis multiplex congenita cannot always be predicted with certainty. (J Child Neurol 2001;16:934–936). [ABSTRACT FROM AUTHOR]

Vitamin B12 is a water-soluble vitamin that plays a fundamental role as an essential cofactor for two enzymes responsible for the production of succinyl-CoA and methionine. Vitamin B12 deficiency can occur in infants and may be related to the breastfeeding mother's adherence to a vegan diet or somatic diseases in the mother. It should be differentiated from inborn errors of vitamin B12 metabolism. Herein, we report the cases of three infants with West syndrome; all three were breastfed by mothers who followed a strict vegan diet. In one of the three infants, West syndrome developed during treatment with vitamin B12 and normalization of the vitamin B12 level. Early treatment and replacement therapy are worthwhile to prevent serious neurological problems and to improve the patient's clinical course. [ABSTRACT FROM AUTHOR]

Background: Vaccine coverage of health care professionals against influenza is still low in Italy, as well as in other European countries. Methods: Between March and May 2018, this study was performed to collect the opinions of Pediatric health care professionals, working in emergency departments, regarding the efficacy and safety of the influenza vaccine. An anonymous online survey was employed to evaluate socio-demographic and professional characteristics, knowledges, beliefs and attitudes. Results: Five hundred four health care professionals completed the survey: 331 physicians, 140 nurses and 33 other health are professionals. During the 2017–18 season, 55.8% of physicians, 19.3% of nurses and 12.1% of other health care professionals had vaccinated against the influenza virus. Not vaccinated physicians and nurses with less than 40 years of age were fewer than not vaccinated physicians and nurses with more than 40 years of age. Nurses and other health care professionals were less trustworthy of the influenza vaccination, less aware of the possibility of contracting and transmitting influenza and other vaccine-preventable diseases. Conclusions: Insufficient adherence to the influenza vaccination in physicians, nurses and other health care professionals is a concern for those assisting high-risk patients, especially in emergency departments. Therefore, it is vital to promote education of health care professionals and students regarding vaccinations. High vaccine coverage should be embedded in the safe hospital paradigm and should become a goal for the hospital's directors. [ABSTRACT FROM AUTHOR]

Neonatal seizures are the most common neurological event in newborns, showing higher prevalence in preterm than in full-term infants. In the majority of cases they represent acute symptomatic phenomena, the main etiologies being intraventricular haemorrhage, hypoxic-ischemic encephalopathy, central nervous system infections and transient metabolic derangements. Current definition of neonatal seizures requires detection of paroxysmal EEG-changes, and in preterm newborns the incidence of electrographic-only seizures seems to be particularly high, further stressing the crucial role of electroencephalogram monitoring in this population. Imaging work-up includes an integration of serial cranial ultrasound and brain magnetic resonance at term-equivalent age. Unfavourable outcomes following seizures in preterm infants include death, neurodevelopmental impairment, epilepsy, cerebral palsy, hearing and visual impairment. As experimental evidence suggests a detrimental role of seizures per se in determining subsequent outcome, they should be promptly treated with the aim to reduce seizure burden and long-term disabilities. However, neonatal seizures show low response to conventional anticonvulsant drugs, and this is even more evident in preterm newborns, due to intrinsic developmental factors. As a consequence, as literature does not provide any specific guidelines, due to the lack of robust evidence, off-label medications are often administered in clinical practice. [ABSTRACT FROM AUTHOR]

Background Kleefstra syndrome (KS) or 9q34.3 microdeletion syndrome (OMIM #610253) is a rare genetic condition featuring intellectual disability, hypotonia, and dysmorphic facial features. Autism spectrum disorder, severe language impairment, and sleep disorders have also been described. The syndrome can be either caused by a microdeletion in 9q34.3 or by pathogenic variants in the euchromatin histone methyltransferase 1 gene (EHMT1 , *607001). Although epilepsy has been reported in 20 to 30% of subjects, a detailed description of epileptic features and underlying etiology is still lacking. The purpose of this study is to investigate epilepsy features in a cohort of epileptic patients with KS. Methods This multicenter study investigated eight patients with KS and epilepsy. Our findings were compared with literature data. Results We included five patients with 9q or 9q34.33 deletions, a subject with a complex translocation involving EHMT1 , and two with pathogenic EHMT1 variants. All patients presented with moderate to severe developmental delay, language impairment, microcephaly, and infantile hypotonia. Although the epileptic manifestations were heterogeneous, most patients experienced focal seizures. The seizure frequency differs according to the age of epilepsy onset, with patients with early-onset epilepsy (before 36 months of age) presenting more frequent seizures. An overtime reduction in seizure frequency, as well as in antiseizure drug number, was observed in all patients. Developmental delay degree did not correlate with seizure onset and frequency or drug resistance. Conclusion Epilepsy is a frequent finding in KS, but the underlying pathogenetic mechanism and specific features remain elusive. [ABSTRACT FROM AUTHOR]

Preterm infants have an increased risk of cognitive and behavioral deficits and cerebral palsy compared to term born babies. Especially before 32 weeks of gestation, infants may require respiratory support, but at the same time, ventilation is known to induce oxidative stress, increasing the risk of brain injury. Ventilation may cause brain damage through two pathways: localized cerebral inflammatory response and hemodynamic instability. During ventilation, the most important causes of pro-inflammatory cytokine release are oxygen toxicity, barotrauma and volutrauma. The purpose of this review was to analyze the mechanism of ventilation-induced lung injury (VILI) and the relationship between brain injury and VILI in order to provide the safest possible respiratory support to a premature baby. As gentle ventilation from the delivery room is needed to reduce VILI, it is recommended to start ventilation with 21–30% oxygen, prefer a non-invasive respiratory approach and, if mechanical ventilation is required, prefer low Positive End-Expiratory Pressure and tidal volume. [ABSTRACT FROM AUTHOR]

Background: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. Methods: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. Results: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. Conclusion: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought. [ABSTRACT FROM AUTHOR]

The 4q deletion syndrome defines a disorder, which may involve patients affected by either the deletion of the interstitial region from the centromere to 4q31 or by the deletion of the terminal region from 4q31 to 4qter. Here, we describe clinical phenotypes of two unrelated children of the same age followed at the same time, with case 1 presenting with 4q interstitial and case 2 with terminal 4q deletion, and compare them each other and with those reported in the literature. Both children showed complex, heterogeneous clinical manifestations, including craniofacial features, pre-postnatal growth failure, speech and developmental delay. In case 2, thyroid and cholesterol dysfunction were also found. Analyzing these data, clinical differences between interstitial and terminal 4q deletions are scanty and no significant phenotype differences were found between the 4q regions deleted as observed in the comparison of the two children and the related cases of the literature. The term 4q deletion syndrome - inclusive for both the interstitial and terminal 4q regions deleted - seems to be appropriate. To note, the dysfunction of cholesterol metabolism and thyroid presented by case 2 may be clinically worthwhile, whether confirmed by other observations. [ABSTRACT FROM AUTHOR]

Background: It is not yet clear if blood pressure and renal function changes evolve differently in children with a congenital or acquired solitary functioning kidney. This study aims to assess if there are any differences between these two types of solitary kidney patients. Methods: Current research is a retrospective study assessing the evolution of glomerular filtration rate, proteinuria, and blood pressure in clinical records of 55 children with a solitary functioning kidney (37 congenital and 18 acquired). We used the medical records of children who had been assisted, in our unit of pediatric nephrology, for a period of 14 years (168 months), from the time of diagnosis, between January/1997 and December/2015. Results: During the study period, glomerular filtration rate (T0 128.89±32.24 vsT14 118.51 ±34.45 ml/min/1. 73 m², p NS) and proteinuria (T0 85.14 ± 83.13 vs T14 159.03 ± 234.66 mg/m²/die, p NS) demonstrated no significant change. However, after 14 years of follow-up 76.4% of patients had increased levels of arterial hypertension with values over the 90th percentile for gender, age, and height. Specifically, children with an acquired solitary functioning kidney mainly developed hypertension [TO 2/17 (12%) vs T14 9/17 (52.9%) p < 0.025], whereas children with a congenital solitary functioning kidney mainly developed pre-hypertension [T0 3/38 (7.9%) vs T14 17/38 (44.7%) p < 0.0005]. Conclusions: The renal function of children with solitary functioning kidneys remains stable during a follow-up of 14 years. However, these children should be carefully monitored for their tendency to develop arterial blood pressure greater than the 90th percentile for gender, age, and height. [ABSTRACT FROM AUTHOR]

The purpose of this case report and literature review is to describe a case of Adie's pupil associated with variant Dandy-Walker complex (DWC) and to review the literature on the ocular manifestations of Dandy-Walker syndrome and variant Dandy-Walker syndrome. A literature search was conducted using the Pubmed database following the PRISMA guidelines. Inclusion criteria were radiologically confirmed Dandy Walker or Dandy Walker variant patients with ocular anatomical and functional anomalies. Overall, 48 studies met the inclusion criteria for this review, with a total of 634 patients diagnosed with Dandy-Walker syndrome and variant Dandy-Walker syndrome exhibiting a wide range of ocular manifestations. Microphthalmia was the most frequently reported abnormality, while megalocornea was less frequently reported. Of the 48 studies included, only one reported a case of Adie's pupil associated with variant Dandy-Walker complex, as presented in the case report. Ocular involvement in patients with Dandy-Walker syndrome and variant Dandy-Walker syndrome is rare. The authors present a case of variant Dandy-Walker complex associated with Adie's pupil, which has not been reported in the literature previously. The literature review confirms that ocular manifestations are rare but can occur in patients with Dandy-Walker syndrome and variant Dandy-Walker syndrome. Therefore, it is important for clinicians to evaluate patients with these malformations for possible ocular involvement. [ABSTRACT FROM AUTHOR]

FIRES is defined as a disorder that requires a prior febrile infection starting between 2 weeks and 24 h before the onset of the refractory status epilepticus with or without fever at the onset of status epilepticus. The patients, previously normal, present in the acute phase recurrent seizures and status epilepticus followed by a severe course with usually persistent seizures and residual cognitive impairment. Boundary with "new onset refractory status epilepticus (NORSE) has not clearly established. Pathogenetic hypothesis includes inflammatory or autoimmune mechanism with a possible genetic predisposition for an immune response dysfunction. Various types of treatment have been proposed for the treatment of the acute phase of the disorder to block the rapid seizures evolution to status epilepticus and to treat status epilepticus itself. Prognosis is usually severe both for control of the seizures and for cognitive involvement. FIRES is an uncommon but severe disorder which must be carefully considered in the differential diagnosis with other epileptic encephalopathy. [ABSTRACT FROM AUTHOR]