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Objective To determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG). Study design We prospectively collected data from 426 consecutive neonates (56% male, 88% term) ≤44 weeks postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at seven U.S. tertiary care pediatric centers following American Clinical Neurophysiology Society (ACNS) guidelines for cEEG for at risk neonates. Seizure etiology, burden, management and outcome were determined by chart review using a case report form designed at study onset. Results The most common seizure etiologies were hypoxic-ischemic encephalopathy (38%), ischemic stroke (18%), and intracranial hemorrhage (11%). Seizure burden was high, with 59% having ≥7 electrographic seizures and 16% having status epilepticus; 52% received ≥2 anti-seizure medications. During the neonatal admission, 17% died; 49% of survivors had abnormal neurological examination at hospital discharge. In an adjusted analysis, high seizure burden was a significant risk factor for mortality, length of hospital stay, and abnormal neurological examination at discharge. Conclusions In this large contemporary profile of consecutively enrolled newborns with seizures treated at centers using cEEG per ACNS guidelines, about half had high seizure burden, received ≥2 anti-seizure medications, and/or died or had abnormal examination at discharge. Higher seizure burden was associated with increased morbidity and mortality. These findings underscore the importance of accurate determination of neonatal seizure frequency and etiology, and a potential for improved outcome if seizure burden is reduced.

IMPORTANCE Early-life epilepsies are often a consequence of numerous neurodevelopmental disorders, most of which are proving to have genetic origins. The role of genetic testing in the initial evaluation of these epilepsies is not established.OBJECTIVE To provide a contemporary account of the patterns of use and diagnostic yield of genetic testing for early-life epilepsies. DESIGN, SETTING, AND PARTICIPANTSIn this prospective cohort, children with newly diagnosed epilepsy with an onset at less than 3 years of age were recruited from March 1, 2012, to April 30, 2015, from 17 US pediatric hospitals and followed up for 1 year. Of 795 families approached, 775 agreed to participate. Clinical diagnosis of the etiology of epilepsy were characterized based on information available before genetic testing was performed. Added contributions of cytogenetic and gene sequencing investigations were determined.EXPOSURES Genetic diagnostic testing. MAIN OUTCOMES AND MEASURES Laboratory-confirmed pathogenic variant.RESULTS Of the 775 patients in the study (367 girls and 408 boys; median age of onset, 7.5 months [interquartile range, 4.2-16.5 months]), 95 (12.3%) had acquired brain injuries. Of the remaining 680 patients, 327 (48.1%) underwent various forms of genetic testing, which identified pathogenic variants in 132 of 327 children (40.4%; 95% CI, 37%-44%): 26 of 59 (44.1%) with karyotyping, 32 of 188 (17.0%) with microarrays, 31 of 114 (27.2%) with epilepsy panels, 11 of 33 (33.3%) with whole exomes, 4 of 20 (20.0%) with mitochondrial panels, and 28 of 94 (29.8%) with other tests. Forty-four variants were identified before initial epilepsy presentation. Apart from dysmorphic syndromes, pathogenic yields were highest for children with tuberous sclerosis complex (9 of 11 [81.8%]), metabolic diseases (11 of 14 [78.6%]), and brain malformations (20 of 61 [32.8%]). A total of 180 of 446 children (40.4%), whose etiology would have remained unknown without genetic testing, underwent some testing. Pathogenic variants were identified in 48 of 180 children (26.7%; 95% CI, 18%-34%). Diagnostic yields were greater than 15% regardless of delay, spasms, and young age. Yields were greater for epilepsy panels (28 of 96 [29.2%]; P < .001) and whole exomes (5 of 18 [27.8%]; P = .02) than for chromosomal microarray (8 of 101 [7.9%]).CONCLUSIONS AND RELEVANCE Genetic investigations, particularly broad sequencing methods, have high diagnostic yields in newly diagnosed early-life epilepsies regardless of key clinical features. Thorough genetic investigation emphasizing sequencing tests should be incorporated into the initial evaluation of newly presenting early-life epilepsies and not just reserved for those with severe presentations and poor outcomes.

Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing TH, independent of degree of abnormality on aEEG background. Seizures are common during cooling, particularly on day 1, with a significant rebound on day 4.

When humans and animals compare two numbers, responding is faster and more accurate with increasing numerical disparity and decreasing numerical size. Researchers explaining these distance and size effects often, assume that the subjective number continuum is logarithmically compressed. An alternative hypothesis is that the subjective number continuum is linear, but positions farther along it are proportionately fuzzier, that is, less precisely located. These two hypotheses have been treated as functionally equivalent because of their similar empirical predictions. The current experiment sought to resolve this issue with a paradigm originally developed to address the subjective representation of time (time left). In our adaptation, pigeons were required to compare a constant number with the number remaining after a numerical subtraction. Our results indicate that subjective number is linearly, not logarithmically, related to objective number.

Electrographic seizures are common in neonates with hypoxic-ischemic encephalopathy, but detailed data are not available regarding seizure incidence during therapeutic hypothermia. The objective of this prospective study was to determine the incidence and timing of electrographic seizures in term neonates undergoing whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy as detected by conventional full-array electroencephalography for 72 hours of therapeutic hypothermia and 24 hours of normothermia. Clinical and electroencephalography data were collected from 26 consecutive neonates. Electroencephalograms were reviewed by 2 pediatric neurophysiologists. Electrographic seizures occurred in 17 of 26 (65%) patients. Seizures were entirely nonconvulsive in 8 of 17 (47%), status epilepticus occurred in 4 of 17 (23%), and seizure onset was in the first 48 hours in 13 of 17 (76%) patients. Electrographic seizures were common, were often nonconvulsive, and had onset over a broad range of times in the first days of life.