Using Telemedicine to Overcome Barriers to Neurodevelopmental Care from the Neonatal Intensive Care Unit to School Entry.

Dedicated Neonatal Intensive Care Unit (NICU) follow-up programs are recommended for ongoing surveillance for infants at high-risk for future neurodevelopmental impairment (NDI). Systemic, socioeconomic, and psychosocial barriers remain for referrals and the continued neurodevelopmental follow-up of high-risk infants. Telemedicine can help overcome these barriers. Telemedicine allows standardization of evaluations, increased referral rates, and reduced time to follow-up as well as increased therapy engagement. Telemedicine can expand neurodevelopmental surveillance and support all NICU graduates, facilitating the early identification of NDI. However, with the recent expansion of telemedicine during the COVID-19 pandemic, new barriers related to access and technological support have arisen.

Treatment of Neonatal Seizures: Comparison of Treatment Pathways From 11 Neonatal Intensive Care Units.

OBJECTIVE: Seizures are a common neonatal neurologic emergency. Many centers have developed pathways to optimize management. We evaluated neonatal seizure management pathways at level IV neonatal intensive care units (NICUs) in the United States to highlight areas of consensus and describe aspects of variability. METHODS: We conducted a descriptive analysis of 11 neonatal seizure management pathways from level IV NICUs that specialize in neonatal neurocritical care including guidelines for electroencephalography (EEG) monitoring, antiseizure medication (ASM) choice, timing, and dose. RESULTS: Study center NICUs had a median of 70 beds (interquartile range: 52-96). All sites had 24/7 conventional EEG initiation, monitoring, and review capability. Management pathways uniformly included prompt EEG confirmation of seizures. Most pathways included a provision for intravenous benzodiazepine administration if either EEG or loading of ASM was delayed. Phenobarbital 20 mg/kg IV was the first-line ASM in all pathways. Pathways included either fosphenytoin or levetiracetam as the second-line ASM with variable dosing. Third-line ASMs were most commonly fosphenytoin or levetiracetam, with alternatives including topiramate or lacosamide. All pathways provided escalation to continuous midazolam infusion with variable dosing for seizures refractory to initial medication trials. Three pathways also included lidocaine infusion. Nine pathways discussed ASM discontinuation after resolution of acute symptomatic seizures with variable timing. CONCLUSIONS: Despite a paucity of data from controlled trials regarding optimal neonatal seizure management, there are areas of broad agreement among institutional pathways. Areas of substantial heterogeneity that require further research include optimal second-line ASM, dosage, and timing of ASM discontinuation.

Seizures Are Associated With Brain Injury in Infants Undergoing Extracorporeal Membrane Oxygenation.

OBJECTIVE: Determine seizure frequency and association with neurologic outcomes in infants undergoing extracorporeal membrane oxygenation. Identify patient or clinical factors associated with seizures or brain injury on imaging. METHODS: Retrospective, single-center study including infants less than 1 year of age, who underwent extracorporeal membrane oxygenation between 2012 and 2017. RESULTS: A total of 104 infants met study criteria including 45 patients with continuous electroencephalographic (EEG) monitoring during their extracorporeal membrane oxygenation run and 59 infants without EEG. Seizures (electrographic-only or electro-clinical) were identified in 18 of the 45 (40%). Among the 18 infants with seizures, 14 (78%) had moderate to severe brain injury, whereas only 44% of those without seizures (12 of 27) on EEG had moderate to severe brain injury (P = .03). Cardiopulmonary resuscitation prior to extracorporeal membrane oxygenation (ECPR), mode of extracorporeal membrane oxygenation, length of stay, survival to discharge, and congenital heart disease were not associated with seizures. One of 10 patients with cyanotic congenital heart disease due to hypoplastic left heart syndrome had seizures compared with 7 of 10 patients with non-hypoplastic left heart syndrome lesions (P = .02). Seizures were associated with moderate to severe brain injury, after adjusting for ECPR and congenital heart disease (P = .04). CONCLUSIONS: Electrographic seizures were common in patients undergoing extracorporeal membrane oxygenation and higher than previously reported. Seizures were associated with moderate to severe abnormalities on imaging, after adjusting for ECPR and congenital heart disease. This study adds to recent literature describing the risk of seizures in patients on extracorporeal membrane oxygenation and highlights the presence of brain injuries that may be identified by routine EEG surveillance.

Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans.

BACKGROUND: The left and right AWC olfactory neurons in Caenorhabditis elegans differ in their functions and in their expression of chemosensory receptor genes; in each animal, one AWC randomly takes on one identity, designated AWCOFF, and the contralateral AWC becomes AWCON. Signaling between AWC neurons induces left-right asymmetry through a gap junction network and a claudin-related protein, which inhibit a calcium-regulated MAP kinase pathway in the neuron that becomes AWCON. RESULTS: We show here that the asymmetry gene olrn-1 acts downstream of the gap junction and claudin genes to inhibit the calcium-MAP kinase pathway in AWCON. OLRN-1, a protein with potential membrane-association domains, is related to the Drosophila Raw protein, a negative regulator of JNK mitogen-activated protein (MAP) kinase signaling. olrn-1 opposes the action of two voltage-activated calcium channel homologs, unc-2 (CaV2) and egl-19 (CaV1), which act together to stimulate the calcium/calmodulin-dependent kinase CaMKII and the MAP kinase pathway. Calcium channel activity is essential in AWCOFF, and the two AWC neurons coordinate left-right asymmetry using signals from the calcium channels and signals from olrn-1. CONCLUSION: olrn-1 and voltage-activated calcium channels are mediators and targets of AWC signaling that act at the transition between a multicellular signaling network and cell-autonomous execution of the decision. We suggest that the asymmetry decision in AWC results from the intercellular coupling of voltage-regulated channels, whose cross-regulation generates distinct calcium signals in the left and right AWC neurons. The interpretation of these signals by the kinase cascade initiates the sustained difference between the two cells.

The claudin superfamily protein nsy-4 biases lateral signaling to generate left-right asymmetry in C. elegans olfactory neurons.

Early in C. elegans development, signaling between bilaterally symmetric AWC olfactory neurons causes them to express different odorant receptor genes. AWC left-right asymmetry is stochastic: in each animal, either the left or the right neuron randomly becomes AWC(ON), and the other neuron becomes AWC(OFF). Here we show that the nsy-4 gene coordinates the lateral signaling that diversifies AWC(ON) and AWC(OFF) neurons. nsy-4 mutants generate 2 AWC(OFF) neurons, as expected if communication between the AWC neurons is lost, whereas overexpression of nsy-4 results in 2 AWC(ON) neurons. nsy-4 encodes a transmembrane protein related to the gamma subunits of voltage-activated calcium channels and the claudin superfamily; it interacts genetically with calcium channels and antagonizes a calcium-to-MAP kinase cascade in the neuron that becomes AWC(ON). Genetic mosaic analysis indicates that nsy-4 functions both cell-autonomously and nonautonomously in signaling between AWC neurons, providing evidence for lateral signaling and feedback that coordinate asymmetric receptor choice.