Mild Hypoxic-Ischemic Encephalopathy: Can Neurophysiological Monitoring Predict Unfavorable Neurological Outcome? A Systematic Review and Meta-analysis.

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..

Progressive Depletion of B and T Lymphocytes in Patients with Ataxia Telangiectasia: Results of the Italian Primary Immunodeficiency Network.

Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype-phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects.

Neonatal ischemic limb lesions: From etiology to topical nitroglycerine. A case series analysis.

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.

Neonatal seizures as onset of Inborn Errors of Metabolism (IEMs): from diagnosis to treatment. A systematic review.

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.

A novel GABRB3 variant in Dravet syndrome: Case report and literature review.

BACKGROUND: Mutations in GABRB3 have been identified in subjects with different types of epilepsy and epileptic syndromes, including West syndrome (WS), Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), myoclonic-atonic epilepsy (MAE), and others. METHODS AND RESULTS: We herewith report on a girl affected by DS, who has been followed from infancy to the current age of 18 years. Next-generation sequencing (NGS)-based genetic testing for multigene analysis of neurodevelopmental disorders identified two likely de novo pathogenic mutations, a missense variant in GABRB3 gene (c.842 C>T; p.Thr281IIe) and a nonsense variant found in BBS4 gene (c.883 C>T; p.Arg295Ter). CONCLUSION: A likely relationship between the novel GABRB3 gene variant and the clinical manifestations presented by the girl is proposed. Previously, one case of DS and two of DS-like linked with GABRB3 mutations have been reported. To the best of our knowledge, this is the first report of DS associated with this novel variant. A literature review of clinical cases with various types of epileptic encephalopathies (EEs) related to GABRB3 mutations is reported.

Deciphering the Invdupdel(8p) Genotype-Phenotype Correlation: Our Opinion.

The 8p inverted duplication/deletion is a rare chromosomal rearrangement clinically featuring neurodevelopmental delay, mild to severe cognitive impairment, heart congenital defects and brain abnormalities. Patients affected also present typical facial dysmorphisms and skeletal malformations, and it is thought that the composite clinical picture may fall into the chromosomal rearrangement architecture. With the major aim of better framing its related clinical and diagnostic paths, we describe a patient carrying a de novo invdupde[8p] whose clinical features have not been described so far. Hence, through an extensive genotype-phenotype correlation analysis and by reviewing the dedicated scientific literature, we compared our patient's features with those reported in other patients, which allows us to place our proband's expressiveness in an intermediate area, widening the scope of the already known invdupde[8p] genotype-phenotype relationship.