Non-neurophysiologist Physicians and Nurses Can Detect Subclinical Seizures in Children Using a Panel of Quantitative EEG Trends and a Seizure Detection Algorithm.

PURPOSE: This study evaluated the sensitivity of nonconvulsive seizure detection by non-neurophysiologist physicians and nurses using a panel of quantitative EEG (QEEG) trends in the setting of a pediatric intensive care unit. METHODS: Forty-five 1-hour QEEG epochs were obtained retrospectively from 10 patients admitted to the McMaster Children's Hospital pediatric intensive care unit, which included 184 electrographic seizures. Each epoch constituted 4 QEEG trends, a seizure probability marker, automated seizure detector, rhythmicity spectrograms, and amplitude-integrated EEG. Six pediatric residents and 5 pediatric intensive care unit nurses analyzed the epochs for possible seizures after a 15-minute power point presentation. This was compared with the gold standard of a board-certified epileptologist interpreting the conventional EEG data for seizures. RESULTS: Sensitivity of seizure detection for pediatric residents and intensive care unit nurses were 0.90. The specificity was 0.87 and 0.89, respectively. The interrater agreement among the pediatric residents was moderate with a kappa (κ) value of 0.45 (confidence interval: 0.41-0.49), and among the nurses were moderate with a κ value of 0.59 (confidence interval: 0.54-0.63). A post hoc analysis involving 2 neurophysiologists demonstrated a sensitivity of 0.90 and a specificity of 0.93 (confidence interval: 0.90-0.96) for seizure detection and a substantial interrater agreement of κ = 0.76 (confidence interval: 0.61-0.91). CONCLUSIONS: A panel of QEEG trends can be used by non-neurophysiologists in a pediatric critical care setting to detect nonconvulsive seizures with a reasonable accuracy, which may expedite subclinical seizure identification and timely intervention.

Epileptic high-frequency oscillations occur in neonates with a high risk for seizures.

Introduction: Scalp high-frequency oscillations (HFOs, 80-250 Hz) are increasingly recognized as EEG markers of epileptic brain activity. It is, however, unclear what level of brain maturity is necessary to generate these oscillations. Many studies have reported the occurrence of scalp HFOs in children with a correlation between treatment success of epileptic seizures and the reduction of HFOs. More recent studies describe the reliable detection of HFOs on scalp EEG during the neonatal period. Methods: In the present study, continuous EEGs of 38 neonates at risk for seizures were analyzed visually for the scalp HFOs using 30 min of quiet sleep EEG. EEGs of 14 patients were of acceptable quality to analyze HFOs. Results: The average rate of HFOs was 0.34 ± 0.46/min. About 3.2% of HFOs occurred associated with epileptic spikes. HFOs were significantly more frequent in EEGs with abnormal vs. normal background activities (p = 0.005). Discussion: Neonatal brains are capable of generating HFOs. HFO could be a viable biomarker for neonates at risk of developing seizures. Our preliminary data suggest that HFOs mainly occur in those neonates who have altered background activity. Larger data sets are needed to conclude whether HFO occurrence is linked to seizure generation and whether this might predict the development of epilepsy.

Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase.

BACKGROUND: WARS2 encodes a tryptophanyl tRNA synthetase, which is involved in mitochondrial protein synthesis. Biallelic mutations in WARS2 are rare and have been associated with a spectrum of clinical presentations, including neurodevelopmental disorder with abnormal movements, lactic acidosis with or without seizures (NEMMLAS). CASE PRESENTATION: Here we present the case of an 8-year-old girl with ataxia and parkinsonism with periventricular white matter abnormalities on magnetic resonance imaging (MRI) and global developmental delay. The initial investigations revealed an elevated lactate level. Extensive metabolic testing, including a muscle biopsy, was inconclusive. Cerebrospinal fluid (CSF) neurotransmitter levels were low; however, a trial of levodopa was unremarkable. The chromosomal microarray and initial ataxia gene panel was normal. Zinc supplementation for a heterozygous variant of unknown significance in the CP gene on the ataxia exome panel was not effective in treating her symptoms. Reanalysis of the ataxia exome panel highlighted biallelic mutations in WARS2, which lead to the diagnosis of neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS). This lead to parental genetic testing, redirected therapy, and helped to expand the symptomology of this rare condition. CONCLUSION: Here we emphasize the importance of imminent and repeat expanded genetic testing to ensure early diagnosis and treatment for rare pediatric disorders. The patient is being trialed on a mitochondrial cocktail in an attempt to compensate for defects in mitochondrial protein synthesis associated with this variant. Longitudinal monitoring of disease manifestation will help establish the currently unknown natural history of this condition.