Neonatal seizures: aetiology by means of a standardized work-up.

UNLABELLED: Neonatal seizures are an alarming symptom and are frequent in neonates. It is important to find the cause of neonatal seizures to start a specific treatment and to give a meaningful prognosis. The aim of this study is to investigate the incidence of different aetiologies of neonatal seizures in our hospital by a specific work-up. METHODS: All full-term born neonates from January 2002 till September 2009 with neonatal seizures, admitted to our neonatal intensive care unit were included (n = 221). Aetiology was investigated by means of a standardized aetiologic work-up. RESULTS: The frequencies of aetiologies of neonatal seizures were: hypoxic-ischemic encephalopathy (HIE) (n = 119; 53.9%), metabolic or electrolyte disorders (n = 24; 10.9%), intracranial hemorrhage (n = 20; 9.0%), ischemic infarction (n = 16; 7.2%), intracranial infections (n = 14; 6.3%), congenital malformations of the central nervous system (n = 7; 3.2%), inborn errors of metabolism (n = 5; 2.3%), epileptic syndromes (n = 1; 0.5%), HIE + hypoglycemia (n = 4; 1.8%), HIE + intracranial hemorrhage (n = 3; 1.4%), HIE + ischemic infarction (n = 1; 0.5%), ischemic infarction + intracranial hemorrhage (n = 1; 0.5%), idiopathic (n = 4, 1.8%), intoxications (n = 1; 0.5%) and unknown (n = 1; 0.5%). CONCLUSION: Our work-up is a practical tool to find the aetiology of neonatal seizures.

Introduction of hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders.

BACKGROUND: Therapeutic hypothermia was introduced in the Netherlands and Flanders, Belgium, in 2008. Since then, an increasing number of patients has been treated - up to 166 in 2010. Complications and outcome were registered in an online database. OBJECTIVES: The aim of this study was to analyse complications and outcome after implementation. METHODS: Data were retrieved from an online database to which all centres had contributed. RESULTS: In 3 years, 332 patients were treated. Excluding 24 patients with congenital abnormalities or metabolic disorders, mortality was 31.8%. Of the 210 survivors without congenital malformations, 21 had cerebral palsy, another 19 a developmental delay of more than 3 months at the age of at least 24 months, and 2 had severe hearing loss. The total adverse outcome, combining death and adverse neurodevelopment, in 308 patients without congenital malformations is 45.5%, which is similar to that of the large trials. CONCLUSIONS: The introduction of therapeutic hypothermia for neonates with perinatal asphyxia in the Netherlands and Flanders has been rapid and successful, with results similar to findings in the randomised controlled trials.

Loss of desmoplakin tail causes lethal acantholytic epidermolysis bullosa.

The cytoplasmic plaque protein desmoplakin (DP), which is located in desmosomes, plays a major role in epithelial and muscle cell adhesion by linking the transmembrane cadherins to the cytoplasmic intermediate filament network. Mutations of DP may cause striate palmoplantar keratoderma, arrhythmogenic right ventricular dysplasia, skin fragility/woolly hair syndrome, Naxos-like disease, and Carvajal syndrome. DP must be indispensable, because DP-/- mice are early abortive. Here, we report a patient with severe fragility of skin and mucous membranes caused by genetic truncation of the DP tail. The new phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. The phenotype also comprised universal alopecia, neonatal teeth, and nail loss. Histology showed suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus. Electron microscopy revealed disconnection of keratin intermediate filaments from desmosomes. Immunofluorescence staining of DP showed a distinct punctate intercellular pattern in the patient's skin. Protein analysis revealed expression of truncated DP polypeptides. Mutational analysis of the patient demonstrated compound heterozygosity for two DP mutations, 6079C-->T (R1934X) and 6370delTT, respectively. Aberrant mRNA transcripts that predict premature termination of translation with loss of the three intermediate filament-binding subdomains in the DP tail were detected by RT-PCR. The new dramatic phenotype, which we named "lethal acantholytic epidermolysis bullosa," underscores the paramount role of DP in epidermal integrity.