Comprehensive review of status gelasticus: Diagnostic challenges and therapeutic insights.

Status gelasticus is a rare form of status epilepticus characterized by prolonged and/or clustered gelastic seizures. The review encompasses an analysis of cases reported in the literature, focusing on causes, clinical-electroencephalographic features, and therapeutic interventions. The study reveals the challenges in defining and understanding status gelasticus due to its diverse etiologies and limited reported cases. The association with hypothalamic hamartomas and other brain abnormalities underscores the importance of thorough evaluations. The review also discusses new treatments, including medications and less invasive surgeries. While progress has been made, the study points out challenges in diagnosing and managing this complex condition, highlighting the importance of ongoing research.

The Impact of Genetics on Cognition: Insights into Cognitive Disorders and Single Nucleotide Polymorphisms.

This article explores the complex relationship between genetics and cognition, specifically examining the impact of genetic variants, particularly single nucleotide polymorphisms (SNPs), on cognitive functions and the development of neuropsychiatric disorders. Focusing on neurotransmitter regulation within the prefrontal cortex's dopaminergic circuits, this study emphasizes the role of genes like COMT, PRODH, and DRD in shaping executive functions and influencing conditions such as ADHD and schizophrenia. Additionally, it explores the significance of genetic factors in neurodevelopmental disorders, emphasizing the need for early identification to guide appropriate therapeutic interventions. This article also investigates polymorphisms in the transsulfuration pathway, revealing their association with cognitive impairment diseases. Computational analyses, including machine learning algorithms, are highlighted for their potential in predicting symptom severity in ADHD based on genetic variations. In conclusion, this article underscores the intricate interplay of genetic and environmental factors in shaping cognitive outcomes, providing valuable insights for tailored treatments and a more comprehensive understanding of neuropsychiatric conditions.

Fibroblast Growth Factor Receptor 2 (FGFR2), a New Gene Involved in the Genesis of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a long-known complex neurodevelopmental disorder, and over the past decades, with the enhancement of the research genomic techniques, has been the object of intensive research activity, and many genes involved in the development and functioning of the central nervous system have been related to ASD genesis. Herein, we report a patient with severe ASD carrying a G > A de novo variant in the FGFR2 gene, determining a missense mutation. FGFR2 encodes for the ubiquitous fibroblast growth factor receptor (FGFR) type 2, a tyrosine kinase receptor implicated in several biological processes. The mutated version of this protein is known to be responsible for several variable overlapping syndromes. Even if there still is only sparse and anecdotal data, recent research highlighted a potential role of FGFR2 on neurodevelopment. Our findings provide new insights into the potential causative role of FGFR2 gene in complex neurodevelopmental disorders.

Neurotrophins: Expression of Brain-Lung Axis Development.

Neurotrophins (NTs) are a group of soluble growth factors with analogous structures and functions, identified initially as critical mediators of neuronal survival during development. Recently, the relevance of NTs has been confirmed by emerging clinical data showing that impaired NTs levels and functions are involved in the onset of neurological and pulmonary diseases. The alteration in NTs expression at the central and peripheral nervous system has been linked to neurodevelopmental disorders with an early onset and severe clinical manifestations, often named "synaptopathies" because of structural and functional synaptic plasticity abnormalities. NTs appear to be also involved in the physiology and pathophysiology of several airway diseases, neonatal lung diseases, allergic and inflammatory diseases, lung fibrosis, and even lung cancer. Moreover, they have also been detected in other peripheral tissues, including immune cells, epithelium, smooth muscle, fibroblasts, and vascular endothelium. This review aims to provide a comprehensive description of the NTs as important physiological and pathophysiological players in brain and lung development.

Impact of respiratory viral infections during pregnancy on the neurological outcomes of the newborn: current knowledge.

Brain development is a complex process that begins during pregnancy, and the events occurring during this sensitive period can affect the offspring's neurodevelopmental outcomes. Respiratory viral infections are frequently reported in pregnant women, and, in the last few decades, they have been related to numerous neuropsychiatric sequelae. Respiratory viruses can disrupt brain development by directly invading the fetal circulation through vertical transmission or inducing neuroinflammation through the maternal immune activation and production of inflammatory cytokines. Influenza virus gestational infection has been consistently associated with psychotic disorders, such as schizophrenia and autism spectrum disorder, while the recent pandemic raised some concerns regarding the effects of severe acute respiratory syndrome coronavirus 2 on neurodevelopmental outcomes of children born to affected mothers. In addition, emerging evidence supports the possible role of respiratory syncytial virus infection as a risk factor for adverse neuropsychiatric consequences. Understanding the mechanisms underlying developmental dysfunction allows for improving preventive strategies, early diagnosis, and prompt interventions.

Long-term predictivity of early neurological assessment and developmental trajectories in low-risk preterm infants.

Prematurity represents 10.6% of all births, and although preterm infants usually show adequate neurodevelopmental outcomes, some may develop significant and long-lasting neurological sequelae. Many studies have analyzed predictive factors for developing severe neurodevelopmental impairments (cerebral palsy, other motor and socio-relational disorders such as autism). In this study, 148 preterm infants were enrolled to investigate the neurodevelopmental trajectories in a population of low-risk premature infants using standardized assessment methods. Significant correlations were found between the general movements, the Hammersmith Infant Neurological Examination, and the Griffiths Mental and Development Scales. Moreover, this study showed their validity and predictivity for adverse neurodevelopmental outcomes even in low-risk infants.

KCNQ2-Related Neonatal Epilepsy Treated With Vitamin B6: A Report of Two Cases and Literature Review.

Potassium Voltage-Gated Channel Subfamily Q Member 2 (KCNQ2) gene has been initially associated with "Benign familial neonatal epilepsy" (BFNE). Amounting evidence arising by next-generation sequencing techniques have led to the definition of new phenotypes, such as neonatal epileptic encephalopathy (NEE), expanding the spectrum of KCNQ2-related epilepsies. Pyridoxine (PN) dependent epilepsies (PDE) are a heterogeneous group of autosomal recessive disorders associated with neonatal-onset seizures responsive to treatment with vitamin B6 (VitB6). Few cases of neonatal seizures due to KCNQ2 pathogenic variants have been reported as successfully responding to VitB6. We reported two cases of KCNQ2-related neonatal epilepsies involving a 5-year-old male with a paternally inherited heterozygous mutation (c.1639C>T; p.Arg547Trp), and a 10-year-old female with a de novo heterozygous mutation (c.740C>T; p.Ser247Leu). Both children benefited from VitB6 treatment. Although the mechanisms explaining the efficacy of VitB6 in such patients remain unclear, this treatment option in neonatal-onset seizures is easily taken into account in Neonatal Intensive Care Units (NICUs). Further studies should be conducted to better define clinical guidelines and treatment protocols.

Synaptopathies in Developmental and Epileptic Encephalopathies: A Focus on Pre-synaptic Dysfunction.

The proper connection between the pre- and post-synaptic nervous cells depends on any element constituting the synapse: the pre- and post-synaptic membranes, the synaptic cleft, and the surrounding glial cells and extracellular matrix. An alteration of the mechanisms regulating the physiological synergy among these synaptic components is defined as "synaptopathy." Mutations in the genes encoding for proteins involved in neuronal transmission are associated with several neuropsychiatric disorders, but only some of them are associated with Developmental and Epileptic Encephalopathies (DEEs). These conditions include a heterogeneous group of epilepsy syndromes associated with cognitive disturbances/intellectual disability, autistic features, and movement disorders. This review aims to elucidate the pathogenesis of these conditions, focusing on mechanisms affecting the neuronal pre-synaptic terminal and its role in the onset of DEEs, including potential therapeutic approaches.

Treatment of multiple sclerosis in children: A brief overview.

Multiple sclerosis (MS) is the most common autoimmune, chronic inflammatory demyelinating disorder of the central nervous system. Pediatric-onset MS (POMS), as opposed to adult-onset MS (AOMS), is a rare condition, presenting similar clinical features to AOMS, but a more active course of the disease, with higher relapse rates and greater white and grey matter damage. To date, the therapeutic approaches to treat POMS have been extrapolated from observational studies and data from trials conducted on adults, raising concerns about their efficacy and safety in the pediatric population. Herein, we discuss the most common therapeutic strategies used in POMS management, basing on the individual clinical practice and experience.

Neonatal Seizures: An Overview of Genetic Causes and Treatment Options.

Seizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called 'Neonatal Epilepsies'. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and 'Ohtahara syndrome' (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.

A Novel Homozygous ALG12 Mutation in a Patient with CDG Type Ig: New Report of a Case with a Mild Phenotype.

Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases caused by the deficiency of enzymes involved in the biosynthesis or remodeling of the glycan moieties of glycoconjugates. Most of CDG are autosomal recessive; however, few of them show autosomal dominant or X-linked inheritance. ALG12-CDG is an autosomal recessive inherited defect caused by a deficiency in the α-mannosyltransferase, dolichyl-P-mannose: Man7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (mannosyltransferase 8), which determines Man7GlcNAc2-PP-dolichol accumulation in tissues including fibroblasts. The clinical features of ALG12-CDG include dysmorphic features, developmental delay, hypotonia, progressive microcephaly, hypogammaglobulinemia, coagulopathies, and failure to thrive. Herein, we describe the case of a Sicilian patient with a milder phenotype bearing an ALG12 homozygous mutation. To date, including this patient, only 16 cases have been described with this form of CDG. Furthermore, our study contributes to understanding the milder ALG12-CDG cases and to further expanding the genotype-phenotype spectrum.

Cerebellum and Prematurity: A Complex Interplay Between Disruptive and Dysmaturational Events.

The cerebellum plays a critical regulatory role in motor coordination, cognition, behavior, language, memory, and learning, hence overseeing a multiplicity of functions. Cerebellar development begins during early embryonic development, lasting until the first postnatal years. Particularly, the greatest increase of its volume occurs during the third trimester of pregnancy, which represents a critical period for cerebellar maturation. Preterm birth and all the related prenatal and perinatal contingencies may determine both dysmaturative and lesional events, potentially involving the developing cerebellum, and contributing to the constellation of the neuropsychiatric outcomes with several implications in setting-up clinical follow-up and early intervention.

A Focus on the Cerebellum: From Embryogenesis to an Age-Related Clinical Perspective.

The cerebellum and its functional multiplicity and heterogeneity have been objects of curiosity and interest since ancient times, giving rise to the urge to reveal its complexity. Since the first hypothesis of cerebellar mere role in motor tuning and coordination, much more has been continuously discovered about the cerebellum's circuitry and functioning throughout centuries, leading to the currently accepted knowledge of its prominent involvement in cognitive, social, and behavioral areas. Particularly in childhood, the cerebellum may subserve several age-dependent functions, which might be compromised in several Central Nervous System pathologies. Overall, cerebellar damage may produce numerous signs and symptoms and determine a wide variety of neuropsychiatric impairments already during the evolutive age. Therefore, an early assessment in children would be desirable to address a prompt diagnosis and a proper intervention since the first months of life. Here we provide an overview of the cerebellum, retracing its morphology, histogenesis, and physiological functions, and finally outlining its involvement in typical and atypical development and the age-dependent patterns of cerebellar dysfunctions.