Symptomatic seizures in preterm newborns: a review on clinical features and prognosis

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

Seismic footprints of shallow dyke propagation at Etna, Italy

One of the key issues in forecasting volcanic eruptions is to detect signals that can track the propagation of dykes towards the surface. Continuous monitoring of active volcanoes helps significantly in achieving this goal. The seismic data presented here are unique, as they document surface faulting processes close (tens to a few hundred meters) to their source, namely the dyke tip. They originated nearby - and under - a seismic station that was subsequently destroyed by lava flows during eruptive activity at Etna volcano, Italy, in 2013. On February 20, a ~600 m-long and ~120 m wide NW-SE fracture field opened at an altitude between 2750 and 2900 m. The consequent rock dislocation caused the station to tilt and offset the seismic signal temporarily. Data acquisition continued until the arrival of the lava flow that led to the breakdown of the transmission system. Shallow ground fracturing and repeated low-frequency oscillations occurred during two stages in which the seismic signal underwent a maximum offset ~2.57 E+04 nm/s. Bridging instrumental recordings, fieldwork and conceptual modelling, these data are interpreted as the seismic footprints of a magmatic dyke intrusion that moved at speed ~0.02 m/s (first stage) and 0.46 m/s (second stage)

A clinical review on megalencephaly: A large brain as a possible sign of cerebral impairment.

Megalencephaly and macrocephaly present with a head circumference measurement 2 standard deviations above the age-related mean. However, even if pathologic events resulting in both megalencephaly and macrocephaly may coexist, a distinction between these two entities is appropriate, as they represent clinical expression of different disorders with a different approach in clinical work-up, overall prognosis, and treatment. Megalencephaly defines an increased growth of cerebral structures related to dysfunctional anomalies during the various steps of brain development in the neuronal proliferation and/or migration phases or as a consequence of postnatal abnormal events. The disorders associated with megalencephaly are classically defined into 3 groups: idiopathic or benign, metabolic, and anatomic. In this article, we seek to underline the clinical aspect of megalencephaly, emphasizing the main disorders that manifest with this anomaly in an attempt to properly categorize these disorders within the megalencephaly group

Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience

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 grou

Congenital muscular dystrophy: from muscle to brain.

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

Total Hemi-overgrowth in Pigmentary Mosaicism of the (Hypomelanosis of) Ito Type: Eight Case Reports.

Pigmentary mosaicism of the (hypomelanosis of) Ito type is an umbrella term, which includes phenotypes characterized by mosaic hypopigmentation in the form of streaks, whorls, patchy, or more bizarre skin configurations (running along the lines of Blaschko): these cutaneous patterns can manifest as an isolated skin disorder (pigmentary mosaicism of the Ito type) or as a complex malformation syndrome in association with extracutaneous anomalies (most often of the musculoskeletal and/or nervous systems) (hypomelanosis of Ito). Affected individuals are anecdotally reported to have also partial or total body hemi-overgrowth (HOG), which often causes moderate to severe complications.We studied the occurrence and features of HOG in the 114 children and adults with mosaic pigmentary disorders of the Ito type diagnosed and followed up (from 2 to 22 years; average follow-up 16 years) at our Institutions.Eight patients (5 M, 3 F; aged 4 to 25 years; median age 16 years) out of the 114 analyzed (7%) fulfilled the criteria for unilateral HOG, with differences in diameter ranging from 0.4 to 4.0 cm (upper limbs) and 1.0 to 9.0 cm (lower limbs). Moreover, among these 8 patients, 5/8 filled in the 75th to 90th percentile for height; 6/8 had associated kyphoscoliosis; and 5/8 showed cognitive delays. No tumour complications were recorded. Overall, 6/8 HOG patients presented with additional (extracutaneous) syndromic manifestations, apart from the HOG (ie, with a clinical phenotype of hypomelanosis of Ito).The present study, which includes children and adults with the longest follow-up so far recorded, confirms the association between pigmentary mosaicism of the Ito type and HOG lowering previous estimates (7% vs 16%) for HOG in the context of mosaic hypopigmentation. A careful examination, looking at subtle to moderate asymmetries and associated complications within the spectrum of these mosaic pigmentary disorders, is recommended

PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?

BACKGROUND: Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. CASE PRESENTATION: We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. CONCLUSION: Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation

Flank Instability Phenomena of the Sciara Del Fuoco at Stromboli Volcano, Italy: Recent Evidence From a Multidisciplinary Study

The Sciara del Fuoco (SDF) at Stromboli volcano, located in the western side of the homonymous island, is a deep scar prone to phenomena of flank instability, such as rockfalls and flowing debris. By 30 December, 2002, landslides associated with tsunami waves affected both the sub aerial and submarine part of SDF two days after the onset of a new episode of lava emission. Recently, continuous monitoring as well as frequent structural field survey of SDF have provided an unprecedented opportunity for analyzing similar instability phenomena. Our study combines different data types in a complementary manner by merging geo-structural observations with visual images (taken by a video-cameras surveillance network and vertical air-photos) and seismic records. The goal of this research is to characterize this landslide-prone area for hazard mitigation purposes. The different data types are used to assess how and where SDF morphology changed in the time span from 2002 to 2004. The landslide phenomena of 30 December 2002 deeply eroded the SDF, creating a depression that in some points reached depths of several tens of meters. Afterwards, a reshape process began, through other minor erosive episodes and the deposition of lavas, which were erupted contemporaneously within a part of the collapsed/eroded zone, until the end of the eruption (21 July 2003). The effusion of lavas contributed to fill the depression, stabilizing a wide portion (more than 50 percent) of it and approaching a new gravitational equilibrium. Instead, in the zone of the landslides not reached by the lavas, erosive phenomena have continued to the present day, as evident from the progressive regression of the erosive rim, which has approached the crater zone. These phenomena yielded several rockfalls and flowing debris. Comparative video images and seismic records analysis provides an opportunity to detect the onset of these sliding episodes in time and space, and evaluate the mechanisms of motion. Additionally, this analysis allows us to document numerous explosion quakes and Strombolian explosions conducive to shaking instability. This evidence would result from external (quantity, quality, and position of the potential sliding material) as well as internal changes (location and energy of the seismo-volcanic source) in the volcano

Congenital generalized hypertrichosis: The skin as a clue to complex malformation syndromes

Hypertrichosis is defined as an excessive growth in body hair beyond the normal variation compared with individuals of the same age, race and sex and affecting areas not predominantly androgen-dependent. The term hirsutism is usually referred to patients, mainly women, who show excessive hair growth with male pattern distribution. Hypertrichosis is classified according to age of onset (congenital or acquired), extent of distribution (generalized or circumscribed), site involved, and to whether the disorder is isolated or associated with other anomalies. Congenital hypertrichosis is rare and may be an isolated condition of the skin or a component feature of other disorders. Acquired hypertrichosis is more frequent and is secondary to a variety of causes including drug side effects, metabolic and endocrine disorders, cutaneous auto-inflammatory or infectious diseases, malnutrition and anorexia nervosa, and ovarian and adrenal neoplasms. In most cases, hypertrichosis is not an isolated symptom but is associated with other clinical signs including intellective delay, epilepsy or complex body malformations. A review of congenital generalized hypertrichosis is reported with particular attention given to the disorders where excessive diffuse body hair is a sign indicating the presence of complex malformation syndromes. The clinical course of a patient, previously described, with a 20-year follow-up is reported

From Neonatal Intensive Care to Neurocritical Care: Is It Still a Mirage? The Sicilian Multicenter Project

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