Scalp high-frequency oscillations differentiate neonates with seizures from healthy neonates

OBJECTIVE We aimed to investigate (1) whether an automated detector can capture scalp high-frequency oscillations (HFO) in neonates and (2) whether scalp HFO rates can differentiate neonates with seizures from healthy neonates. METHODS We considered 20 neonates with EEG-confirmed seizures and four healthy neonates. We applied a previously validated automated HFO detector to determine scalp HFO rates in quiet sleep. RESULTS Etiology in neonates with seizures included hypoxic-ischemic encephalopathy in 11 cases, structural vascular lesions in 6, and genetic causes in 3. The HFO rates were significantly higher in neonates with seizures (0.098 ± 0.091 HFO/min) than in healthy neonates (0.038 ± 0.025 HFO/min; P = 0.02) with a Hedge's g value of 0.68 indicating a medium effect size. The HFO rate of 0.1 HFO/min/ch yielded the highest Youden index in discriminating neonates with seizures from healthy neonates. In neonates with seizures, etiology, status epilepticus, EEG background activity, and seizure patterns did not significantly impact HFO rates. SIGNIFICANCE Neonatal scalp HFO can be detected automatically and differentiate neonates with seizures from healthy neonates. Our observations have significant implications for neuromonitoring in neonates. This is the first step in establishing neonatal HFO as a biomarker for neonatal seizures

Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study

BACKGROUND Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol. METHODS We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020. RESULTS First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001). CONCLUSIONS Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses

Scalp HFO rates are higher for larger lesions

High frequency oscillations (HFO) in scalp EEG are a new and promising non-invasive epilepsy biomarker, providing added prognostic value, particularly in pediatric lesional epilepsy. However, it is unclear if lesion characteristics, such as lesion volume, depth, type, and localization, impact scalp HFO rates. We analyzed scalp EEG from 13 children and adolescents with focal epilepsy associated with focal cortical dysplasia (FCD), low-grade tumors, or hippocampal sclerosis. We applied a validated automated detector to determine HFO rates in bipolar channels. We identified the lesion characteristics in MRI. Larger lesions defined by MRI volumetric analysis corresponded to higher cumulative scalp HFO rates (p=0.01) that were detectable in a higher number of channels (p=0.05). Both superficial and deep lesions generated HFO detectable in the scalp EEG. Lesion type (FCD vs. tumor) and lobar localization (temporal vs. extratemporal) did not affect scalp HFO rates in our study. Our observations support that all lesions may generate HFO detectable in scalp EEG, irrespective of their characteristics, whereas larger epileptogenic lesions generate higher scalp HFO rates over larger areas that are thus more accessible to detection. Our study provides crucial insight into scalp HFO detectability in pediatric lesional epilepsy, facilitating their implementation as an epilepsy biomarker in a clinical setting

Lesion Extent Negatively Impacts Intellectual Skills in Pediatric Focal Epilepsy

BACKGROUND Cognitive development in children and adolescents with focal lesional epilepsy is determined by the underlying epileptogenic lesion, in addition to epilepsy itself. However, the impact of lesion-related variables on intelligence quotient (IQ) and developmental quotient (DQ) remains largely unexplored. Here, we aimed to determine the effect of lesion-related predictors and their relation with epilepsy-related predictors of intellectual functioning. METHODS We retrospectively analyzed data from children with focal lesional epilepsy who underwent standardized cognitive evaluation yielding IQ/DQ in our institution. RESULTS We included 50 consecutive patients aged 0.5 to 17.5 years (mean, 9.3; S.D., 4.9) at cognitive assessment. Epilepsy duration was 0 to 15.5 years (mean, 3.8; S.D., 4.1). Of the total cohort, 30 (60%) patients had unilobar lesions, seven (14%) multilobar, 10 (20%) hemispheric, and three (6%) bilateral. Etiology was congenital in 32 (64%) cases, acquired in 14 (28%), and progressive in four (8%). For patients with unilobar lesions, the mean IQ/DQ was 97.1 ± 15.7, for multilobar 98.9 ± 20.2, for hemispheric 76.1 ± 20.5, and for bilateral 76.3 ± 4.5. Larger lesion extent, earlier epilepsy onset, and longer epilepsy duration correlated with lower IQ/DQ in the univariate analysis, whereas only lesion extent and epilepsy duration contributed significantly to the explanatory model in the multivariable analysis. CONCLUSIONS The present study demonstrates that lesion extent and epilepsy duration are important risk factors for intellectual impairment in pediatric patients with focal lesional epilepsy. These findings are useful for family counseling and the early consideration of interventions that may limit the duration of epilepsy

Not surgical technique, but etiology, contralateral MRI, prior surgery, and side of surgery determine seizure outcome after pediatric hemispherotomy

OBJECTIVE: We aimed to assess determinants of seizure outcome following pediatric hemispherotomy in a contemporary cohort. METHODS: We retrospectively analyzed the seizure outcomes of 457 children who underwent hemispheric surgery in five European epilepsy centers between 2000 and 2016. We identified variables related to seizure outcome through multivariable regression modeling with missing data imputation and optimal group matching, and we further investigated the role of surgical technique by Bayes factor (BF) analysis. RESULTS: One hundred seventy seven children (39%) underwent vertical and 280 children (61%) underwent lateral hemispherotomy. Three hundred forty-four children (75%) achieved seizure freedom at a mean follow-up of 5.1 years (range 1 to 17.1). We identified acquired etiology other than stroke (odds ratio [OR] 4.4, 95% confidence interval (CI) 1.1-18.0), hemimegalencephaly (OR 2.8, 95% CI 1.1-7.3), contralateral magnetic resonance imaging (MRI) findings (OR 5.5, 95% CI 2.7-11.1), prior resective surgery (OR 5.0, 95% CI 1.8-14.0), and left hemispherotomy (OR 2.3, 95% CI 1.3-3.9) as significant determinants of seizure recurrence. We found no evidence of an impact of the hemispherotomy technique on seizure outcome (the BF for a model including the hemispherotomy technique over the null model was 1.1), with comparable overall major complication rates for different approaches. SIGNIFICANCE: Knowledge about the independent determinants of seizure outcome following pediatric hemispherotomy will improve the counseling of patients and families. In contrast to previous reports, we found no statistically relevant difference in seizure-freedom rates between the vertical and horizontal hemispherotomy techniques when accounting for different clinical features between groups

Scalp high-frequency oscillation rates are higher in younger children

High-frequency oscillations in scalp EEG are promising non-invasive biomarkers of epileptogenicity. However, it is unclear how high-frequency oscillations are impacted by age in the paediatric population. We prospectively recorded whole-night scalp EEG in 30 children and adolescents with focal or generalized epilepsy. We used an automated and clinically validated high-frequency oscillation detector to determine ripple rates (80-250 Hz) in bipolar channels. Children < 7 years had higher high-frequency oscillation rates (P = 0.021) when compared with older children. The median test-retest reliability of high-frequency oscillation rates reached 100% (iqr 50) for a data interval duration of 10 min. Scalp high-frequency oscillation frequency decreased with age (r = -0.558, P = 0.002), whereas scalp high-frequency oscillation duration and amplitude were unaffected. The signal-to-noise ratio improved with age (r = 0.37, P = 0.048), and the background ripple band activity decreased with age (r = -0.463, P = 0.011). We characterize the relationship of scalp high-frequency oscillation features and age in paediatric patients. EEG intervals of 10 min duration are required for reliable measurements of high-frequency oscillation rates. This study is a further step towards establishing scalp high-frequency oscillations as a valid epileptogenicity biomarker in this vulnerable age group

A patchwork interspersed sequence is present in a high copy number in the sheep genome

We have isolated a new interspersed sequence present in a high copy number in the ovine genome. This patchwork sequence, named 3.79 AS1, is part of a larger element encompassing similarities to constant region of reverse transcriptase and to art2 shared with the Bovine Dimer Driven Family (BDDF). The 3.79 AS1 sequence includes homologies to amplification promoting sequences (APS), to a potential origin of bidirectional DNA replication (OBR), to the Alu core sequence motif GGAGGC required for RNA polymerase III promoter function and to the ATGGCTGCCAT sequence that has been shown to be able to induce amplification-dependent transformation in murine cells. Fluorescent in situ hybridization experiments using probes derived from both ends of the 3.79 AS1 sequence showed a widespread signal over all sheep chromosomes, except the Y chromosome. We propose that the structural features of the 3.79 AS1 patchwork sequence, that is likely to be a subfamily of Bov B LINE that invaded the Artiodactyl genome prior to the separation of the Bovidae species, facilitated its massive amplification and dispersion in the ovine genome