"Electro-clinical Syndromes" with onset in Paediatric Age. the highlights of the clinical-EEG, genetic and therapeutic advances

The genetic causes underlying epilepsy remain largely unknown, and the impact of available genetic data on the nosology of epilepsy is still limited. Thus, at present, classification of epileptic disorders should be mainly based on electroclinical features. Electro-clinical syndrome is a term used to identify a group of clinical entities showing a cluster of electro-clinical characteristics, with signs and symptoms that together define a distinctive, recognizable, clinical disorder. These often become the focus of treatment trials as well as of genetic, neuropsychological, and neuroimaging investigations. They are distinctive disorders identifiable on the basis of a typical age onset, specific EEG characteristics, seizure types, and often other features which, when taken together, permit a specific diagnosis which, in turn, often has implications for treatment, management, and prognosis. Each electro-clinical syndrome can be classified according to age at onset, cognitive and developmental antecedents and consequences, motor and sensory examinations, EEG features, provoking or triggering factors, and patterns of seizure occurrence with respect to sleep. Therefore, according to the age at onset, here we review the more frequently observed paediatric electro-clinical syndrome from their clinical-EEG, genetic and therapeutic point of views

Understanding Childhood Neuroimmune Diseases of the Central Nervous System

Immune-mediated diseases of the central nervous system (CNS) in childhood are a heterogeneous group of rare conditions sharing the inflammatory involvement of the CNS. This review highlights the growing knowledge of childhood neuroimmune diseases that primarily affect the CNS, outlining the clinical and diagnostic features, the pathobiological mechanisms and genetics, current treatment options, and emerging challenges. The clinical spectrum of these conditions is increasingly expanded, and the underlying mechanisms of dysregulation of the immune system could vary widely. Cell-mediated and antibody-mediated disorders, infection-triggered and paraneoplastic conditions, and genetically defined mechanisms can occur in previously healthy children and can contribute to different stages of the disease. The careful evaluation of the clinical presentation and temporal course of symptoms, the specific neuroimaging and immunological findings, and the exclusion of alternative causes are mandatory in clinical practice for the syndromic diagnosis. A common feature of these conditions is that immunotherapeutic agents could modulate the clinical course and outcomes of the disease. Furthermore, specific symptomatic treatments and comprehensive multidisciplinary care are needed in the overall management. We focus on recent advances on immune-mediated demyelinating CNS disorders, autoimmune encephalitis, interferonopathies, and possible neuroimmune disorders as Rasmussen encephalitis. Better knowledge of these conditions could allow prompt diagnosis and targeted immunotherapy, to decrease morbidity and mortality as well as to improve clinical outcomes, reducing the burden of the disease due to possible long-term neuropsychiatric sequelae. Persisting controversies remain in the rigorous characterization of each specific clinical entity because of the relative rarity in children; moreover, in a large proportion of suspected neuroimmune diseases, the immune "signature" remains unidentified; treatment guidelines are mostly based on retrospective cohort studies and expert opinions; then advances in specific molecular therapies are required. In the future, a better characterization of specific immunological biomarkers may provide a useful understanding of the underlying pathobiological mechanisms of these conditions in order to individualize more tailored therapeutic options and paradigms. Multicenter collaborative research on homogeneous groups of patients who may undergo immunological studies and therapeutic trials could improve the characterization of the underlying mechanisms, the specific phenotypes, and tailored management

The molecular chaperone Hsp90 is a component of the cap-binding complex and interacts with the translational repressor Cup during Drosophila oogenesis

In metazoa, the spatio-temporal translation of diverse mRNAs is essential to guarantee proper oocyte maturation and early embryogenesis. The eukaryotic translation initiation factor 4E (eIF4E), which binds the 5′ cap structure of eukaryotic mRNAs, associates with either stimulatory or inhibitory factors to modulate protein synthesis. In order to identify novel factors that might act at the translational level during Drosophila oogenesis, we have undertaken a functional proteomic approach and isolated the product of the Hsp83 gene, the evolutionarily conserved chaperone Hsp90, as a specific component of the cap-binding complex. Here we report that Hsp90 interacts in vitro with the translational repressor Cup. In addition, we show that Hsp83 and cup interact genetically, since lowering Hsp90 activity enhances the oogenesis alterations linked to diverse cup mutant alleles. Hsp90 and Cup co-localize in the cytoplasm of the developing germ-line cells within the germarium, thus suggesting a common function from the earliest stages of oogenesis. Taken together, our data start elucidating the role of Hsp90 during Drosophila female germ-line development and strengthen the idea that Cup has multiple essential functions during egg chamber development

Gastaut type-idiopathic childhood occipital epilepsy and childhood absence epilepsy: a clinically significant association?

We report an unusual association between idiopathic occipital epilepsy and childhood absence epilepsy in 2 pediatric patients. At first clinical and electroencephalographic evaluation, the patients presented the peculiar signs of idiopathic occipital epilepsy Gastaut type: focal sensory visual seizures, migrainelike symptoms (only in one patient) and unilateral spike–wave discharges over occipital regions. Both children were treated with valproic acid and their seizures were rapidly controlled. After a seizure-free period, the patients presented typical absence with ictal electroencephalographies showing 3 cycles/s generalized and symmetrical spike–wave complexes. We discuss the possible association between these two epileptic syndromes and its common pathophysiological mechanisms

Peroxisome Proliferator-Activated Receptors as Mediators of Phthalate-Induced Effects in the Male and Female Reproductive Tract: Epidemiological and Experimental Evidence

There is growing evidence that male as well as female reproductive function has been declining in human and wildlife populations over the last 40 years. Several factors such as lifestyle or environmental xenobiotics other than genetic factors may play a role in determining adverse effects on reproductive health. Among the environmental xenobiotics phthalates, a family of man-made pollutants are suspected to interfere with the function of the endocrine system and therefore to be endocrine disruptors. The definition of endocrine disruption is today extended to broader endocrine regulations, and includes activation of metabolic sensors, such as the peroxisome proliferator-activated receptors (PPARs). Toxicological studies have shown that phthalates can activate a subset of PPARs. Here, we analyze the epidemiological and experimental evidence linking phthalate exposure to both PPAR activation and adverse effects on male and female reproductive health

Cognitive and linguistic abnormalities in benign childhood epilepsy with centrotemporal spikes

Aim: To assess the cognitive function and language ability in children with benign partial epilepsy with centrotemporal spikes. Methods: Twenty-five patients with benign partial epilepsy with centrotemporal spikes were included. They were divided into two subgroups. Group I: 10 patients with rolandic focus who were not treated. Group II: 15 patients with rolandic focus receiving treatment. A third Group of 12 healthy subjects have been studied. All children underwent standardized neuropsychological testing: electroencephalogram recording, Wechsler Intelligence Scale for Children-revised, Peabody Picture Vocabulary Test-III (PPVT-III) and Boston Naming Test (BNT), both during active disease (T1) and 2 years after recovery from epilepsy (T2). Results: At T1 evaluation, no significant differences in group I and II patients about general intelligence, when compared with controls, were found. Group I and II patients were impaired with respect to controls in the receptive and expressive vocabulary evaluated with PCVT-III and BNT, respectively. At T2 evaluation, group I and II patients showed a normalization of the language abnormalities. Conclusion: Deficits of speech-related abilities can be detected in children with this type of epilepsy: these dysfunctions seem to be independent of the effects of antiepileptic treatment and are reversible after remission of epilepsy

Mother to child transmission of Hepatitis C Virus in a province of Northern Italy

NTRODUCTION: Study reports of mother to child transmission of hepatitis C virus (HCV) have shown transmission rates ranging from 3 to 37%, according to maternal viremia and HIV-1 coinfection. The present study evaluated the prevalence of the HCV infection in the general population and the incidence of vertical transmission, from women who delivered in the Obstetric Clinic of the Hospital of Parma from January 1st 1996 to 31st 2001 December. METHODS: Mothers and children were tested for the presence of HCV-RNA within one week after delivery. Children were considered to be infected when they were found positive at least twice for viral RNA or antibodies were still detectable at the end of the follow-up period (18 months) in blood. RESULTS: Out of 13,025 women, 110 (0.8%) were found positive for anti-HCV antibodies; 72 of them (65.4%) were HCV-RNA positive. All 110 children were positive for anti-HCV antibodies in the first blood sample (time 0); 8 of them were HCV-RNA positive. Three children were still viremic at the end of the follow-up whereas 5 showed a clearance. No significant differences were found between viremic and nonviremic children with respect to gestational week, maternal alanine aminotransferase (ALT) levels and newborns weight at birth. CONCLUSION: This investigation shows that vertical transmission may occur in a general obstetric population despite a low prevalence of HCV-positive subjects