Trametinib restores the central conducting lymphatic flow in a premature infant with Noonan syndrome.

We describe a premature hydropic infant with Noonan syndrome and a therapy refractory chylothorax. This was shown to be due to a central conducting lymphatic anomaly. After therapy with a MEK-inhibitor the infant recovered clinically and radiologically completely, possibly by restoring lymphatic valve function.

Temporal evolution of electrographic seizures in newborn infants with hypoxic-ischaemic encephalopathy requiring therapeutic hypothermia: a secondary analysis of the ANSeR studies.

Background: Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome.

Methods: This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]).

Early recognition of characteristic conventional and amplitude-integrated EEG patterns of seizures in SCN2A and KCNQ3-related epilepsy in neonates.

Purpose: Early recognition of seizures in neonates secondary to pathogenic variants in potassium or sodium channel coding genes is crucial, as these seizures are often resistant to commonly used anti-seizure medications but respond well to sodium channel blockers. Recently, a characteristic ictal amplitude-integrated electroencephalogram (aEEG) pattern was described in neonates with KCNQ2-related epilepsy. We report a similar aEEG pattern in seizures caused by SCN2A- and KCNQ3-pathogenic variants, as well as conventional EEG (cEEG) descriptions.

Outcome of non-cooled asphyxiated infants with under-recognised or delayed-onset encephalopathy.

Objective: To describe the clinical characteristics, MRI findings and neurodevelopmental outcome of infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who were not selected for therapeutic hypothermia (TH).

Design: Retrospective cohort study.

Setting And Patients: (Near-)term infants with documented perinatal asphyxia referred to two Dutch level III neonatal units with neonatal encephalopathy (NE) and seizures <24 hours after birth not treated with TH.

Neonatal Seizure Management: Is the Timing of Treatment Critical?

Objective: To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden and describe overall seizure management in a large neonatal cohort.

Study Design: Newborns (36-44 weeks of gestation) requiring electroencephalographic (EEG) monitoring recruited to 2 multicenter European studies were included. Infants who received antiseizure medication exclusively after electrographic seizure onset were grouped based on the time to treatment of the first seizure: antiseizure medication within 1 hour, between 1 and 2 hours, and after 2 hours.

Increased Use of Therapeutic Hypothermia in Infants with Milder Neonatal Encephalopathy due to Presumed Perinatal Asphyxia.

Introduction: Adverse outcomes have been reported in infants with mild neonatal encephalopathy (NE). Increasing clinical experience with the application of therapeutic hypothermia (TH) may have resulted in the treatment of newborns with milder NE during recent years.

Objective: To determine whether infants treated with TH in the initial years following implementation had a higher degree of NE than infants treated during subsequent years.

Delay in Treatment of Neonatal Seizures: A Retrospective Cohort Study.

Introduction: Neonatal seizures are common and caused by a variety of underlying disorders. There is increasing evidence that neonatal seizures result in further brain damage.

Objective: To describe the time interval between diagnosis of amplitude-integrated electroencephalography (aEEG)-confirmed seizures and administration of anti-epileptic drugs (AEDs).

The development and validation of a cerebral ultrasound scoring system for infants with hypoxic-ischaemic encephalopathy.

Background: Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality in neonates. When the gold standard MRI is not feasible, cerebral ultrasound (CUS) might offer an alternative. In this study, the association between a novel CUS scoring system and neurodevelopmental outcome in neonates with HIE was assessed.

Perinatal thalamic injury: MRI predictors of electrical status epilepticus in sleep and long-term neurodevelopment.

Objective: Perinatal thalamic injury is associated with epilepsy with electrical status epilepticus in sleep (ESES). The aim of this study was to prospectively quantify the risk of ESES and to assess neuroimaging predictors of neurodevelopment.

Methods: We included patients with perinatal thalamic injury.

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

Objective: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres.

Methods: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014.

Amplitude-Integrated Electroencephalography for Early Recognition of Brain Injury in Neonates with Critical Congenital Heart Disease.

Objective: To study perioperative amplitude-integrated electroencephalography (aEEG) as an early marker for new brain injury in neonates requiring cardiac surgery for critical congenital heart disease (CHD).

Study Design: This retrospective observational cohort study investigated 76 neonates with critical CHD who underwent neonatal surgery. Perioperative aEEG recordings were evaluated for background pattern (BGP), sleep-wake cycling (SWC), and ictal discharges.

A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia.

Objective: To assess the predictive value of a novel magnetic resonance imaging (MRI) score, which includes diffusion-weighted imaging as well as assessment of the deep grey matter, white matter, and cerebellum, for neurodevelopmental outcome at 2 years and school age among term infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

Study Design: This retrospective cohort study (cohort 1, The Netherlands 2008-2014; cohort 2, Sweden 2007-2012) including infants born at >36 weeks of gestational age treated with therapeutic hypothermia who had an MRI in the first weeks of life. The MRI score consisted of 3 subscores: deep grey matter, white matter/cortex, and cerebellum.

Rhythmic EEG patterns in extremely preterm infants: Classification and association with brain injury and outcome.

Objective: Classify rhythmic EEG patterns in extremely preterm infants and relate these to brain injury and outcome.

Methods: Retrospective analysis of 77 infants born <28 weeks gestational age (GA) who had a 2-channel EEG during the first 72 h after birth. Patterns detected by the BrainZ seizure detection algorithm were categorized: ictal discharges, periodic epileptiform discharges (PEDs) and other waveforms.

A Distinctive Ictal Amplitude-Integrated Electroencephalography Pattern in Newborns with Neonatal Epilepsy Associated with KCNQ2 Mutations.

Background: Recurrent and prolonged seizures are harmful for the developing brain, emphasizing the importance of early seizure recognition and effective therapy. Amplitude-integrated electroencephalography (aEEG) has become a valuable tool to diagnose epileptic seizures, and, in parallel, genetic etiologies are increasingly being recognized, changing the paradigm of the workup and management of neonatal seizures.

Objective: To report the ictal aEEG pattern in neonates with KCNQ2-related epilepsy.

Effect of general anesthesia on neonatal aEEG-A cohort study of patients with non-cardiac congenital anomalies.

Introduction: The aim of the current study was to determine the effect of general anesthesia on neonatal brain activity using amplitude-integrated EEG (aEEG).

Methods: A prospective cohort study of neonates (January 2013-December 2015), who underwent major neonatal surgery for non-cardiac congenital anomalies. Anesthesia was administered at the discretion of the anesthetist.

Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm.

Objectives: To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm.

Study Design: This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO (etCO) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy.

A Comparison of the Thompson Encephalopathy Score and Amplitude-Integrated Electroencephalography in Infants with Perinatal Asphyxia and Therapeutic Hypothermia.

Background: In previous studies clinical signs or amplitude-integrated electroencephalography (aEEG)-based signs of encephalopathy were used to select infants with perinatal asphyxia for treatment with hypothermia.

Aim: The objective of this study was to compare Thompson encephalopathy scores and aEEG, and relate both to outcome.

Subjects And Methods: Thompson scores, aEEG, and outcome were compared in 122 infants with perinatal asphyxia and therapeutic hypothermia.

Severe hypercapnia causes reversible depression of aEEG background activity in neonates: an observational study.

Introduction: Elevated carbon dioxide (CO) blood levels have a depressant effect on the central nervous system and can lead to coma in adults. Less is known about the effect of CO on the neurological function of infants.

Objective: To describe the effect of acute severe hypercapnia (PaCO >70 mm Hg) on amplitude-integrated electroencephalography (aEEG) and cerebral oxygenation in newborn infants.

Punctate white matter lesions in full-term infants with neonatal seizures associated with SLC13A5 mutations.

Introduction: Early-onset epileptic encephalopathy caused by biallelic SLC13A5 mutations is characterized by seizure onset in the first days of life, refractory epilepsy and developmental delay. Little detailed information about the brain MRI features is available in these patients.

Methods: Observational study describing the neuro-imaging findings in eight patients (five families) with mutations in the SLC13A5 gene.

Role of EEG background activity, seizure burden and MRI in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischaemic encephalopathy in the era of therapeutic hypothermia.

Objective: To investigate the role of EEG background activity, electrographic seizure burden, and MRI in predicting neurodevelopmental outcome in infants with hypoxic-ischaemic encephalopathy (HIE) in the era of therapeutic hypothermia.

Methods: Twenty-six full-term infants with HIE (September 2011-September 2012), who had video-EEG monitoring during the first 72 h, an MRI performed within the first two weeks and neurodevelopmental assessment at two years were evaluated. EEG background activity at age 24, 36 and 48 h, seizure burden, and severity of brain injury on MRI, were compared and related to neurodevelopmental outcome.

Lidocaine response rate in aEEG-confirmed neonatal seizures: Retrospective study of 413 full-term and preterm infants.

Objective: To investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second- or third-line antiepileptic drug (AED) for neonatal seizures.

Methods: Full-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed <2 h).

Lidocaine-Associated Cardiac Events in Newborns with Seizures: Incidence, Symptoms and Contributing Factors.

Background: Lidocaine is an effective therapy for neonatal seizures; however, it is not widely used, presumably due to the risk of cardiac events.

Objective: To investigate the incidence of cardiac events in full-term and preterm infants receiving lidocaine for seizures.

Methods: Full-term (n = 368) and preterm (n = 153) infants, admitted to a level 3 neonatal intensive care unit from 1992 to 2012, who received lidocaine for seizures were retrospectively studied.