Pharmacologic treatment options for neonatal seizures have expanded over the last two decades and there is no consensus on optimal treatment strategy. We systematically reviewed the published literature to determine which medication(s) are most effective for treating neonatal seizures, by retrieving trials and observational investigations via PubMed (through August 2011) that focused on pharmacological seizure treatment of neonates (≤ 28 days old) and utilized continuous or amplitude-integrated EEG to confirm seizure diagnosis and cessation. Our search identified 557 initial articles and 14 additional studies after reference reviews, with 16 meeting inclusion criteria. Two were randomized trials and only three additional investigations included comparison groups. We found limited evidence regarding the best pharmacologic treatment for neonatal seizures, but were able to devise a treatment algorithm from available data. These findings have the potential to serve both as a clinical reference and inform the design of comparative effectiveness investigations for neonatal antiepileptics.
Background: Extremely-low-birth-weight (ELBW; ≤1,000 g) infants are at high risk for neurodevelopmental impairments. Conventional brain MRI at term-equivalent age is increasingly used for prediction of outcomes. However, optimal prediction models remain to be determined, especially for cognitive outcomes. Objective: The aim was to evaluate the accuracy of a data-driven MRI scoring system to predict neurodevelopmental impairments. Methods: 122 ELBW infants had a brain MRI performed at term-equivalent age. Conventional MRI findings were scored with a standardized algorithm and tested using a multivariable regression model to predict neurodevelopmental impairment, defined as one or more of the following at 18-24 months' corrected age: cerebral palsy, bilateral blindness, bilateral deafness requiring amplification, and/or cognitive/language delay. Results were compared with a commonly cited scoring system. Results: In multivariable analyses, only moderate-to-severe gyral maturational delay was a significant predictor of overall neurodevelopmental impairment (OR: 12.6, 95% CI: 2.6, 62.0; p < 0.001). Moderate-to-severe gyral maturational delay also predicted cognitive delay, cognitive delay/death, and neurodevelopmental impairment/death. Diffuse cystic abnormality was a significant predictor of cerebral palsy (OR: 33.6, 95% CI: 4.9, 229.7; p < 0.001). These predictors exhibited high specificity (range: 94-99%) but low sensitivity (30-67%) for the above outcomes. White or gray matter scores, determined using a commonly cited scoring system, did not show significant association with neurodevelopmental impairment. Conclusions: In our cohort, conventional MRI at term-equivalent age exhibited high specificity in predicting neurodevelopmental outcomes. However, sensitivity was suboptimal, suggesting additional clinical factors and biomarkers are needed to enable accurate prognostication.
Objective This article aims to describe the frequency and characteristics of anticonvulsant medication treatments initiated in the neonatal period. Study Design We analyzed a cohort of neonates with a seizure diagnosis who were discharged from institutions in the Pediatric Health Information System between 2007 and 2016. Adjusted risk ratios and 95% confidence intervals for characteristics associated with neonatal (≤ 28 days postnatal) anticonvulsant initiation were calculated via modified Poisson regression. Results A total of 6,245 infants from 47 institutions were included. There was a decrease in both phenobarbital initiation within the neonatal period (96.9 to 91.3%, p = 0.015) and continuation at discharge (90.6 to 68.6%, p <0.001). Levetiracetam (7.9 to 39.6%, p < 0.001) initiation within the neonatal period and continuation at discharge (9.4 to 49.8%, p < 0.001) increased. Neonates born at ≥ 37 weeks' gestation and those diagnosed with intraventricular hemorrhage, ischemic/thrombotic stroke, other hemorrhagic stroke, and hypoxic ischemic encephalopathy (HIE) had a higher probability of anticonvulsant administration. The most prevalent diagnosis was HIE (n = 2,223, 44.4%). Conclusion Phenobarbital remains the most widely used neonatal seizure treatment. Levetiracetam is increasingly used as a second line therapy. Increasing levetiracetam use indicates a need for additional study to determine its effectiveness in reducing seizure burden and improving long-term outcomes.
Consequences of neonatal cerebral venous infarct can be severe. However, we have identified a series of neonates with unilateral temporal lobe infarcts, suspected to be secondary to superficial cortical venous thrombosis, who have had relatively normal outcomes. Medical records were reviewed retrospectively. History, relevant studies, and outcomes for 7 patients are described. Most patients presented with neonatal seizures. Neuroimaging showed unilateral temporal lobe hemorrhage and surrounding ischemic change, which was initially attributed to thrombosis of the vein of Labbe; however, magnetic resonance venogram findings suggest that thrombosis of other superficial temporal lobe veins may also be involved. Seizure control was achieved in all cases. Development and neurologic examination at follow-up were usually normal. We conclude that neonatal temporal lobe hemorrhagic infarct secondary to suspected superficial temporal venous thrombosis appears to have a good clinical outcome. This is surprising, given the dramatic imaging and clinical presentations.
BACKGROUND The vein of Labbé (VOL) is a superficial cortical vein which drains the lateral surface of the temporal lobe. Thrombosis of the VOL can occur in the neonatal period. The developmental outcomes of infants who had VOL thrombosis are unknown as few studies of outcomes exist. METHODS Retrospective chart review of infants born ≥34 weeks gestation, diagnosed with VOL thrombosis and/or infarction on neuroimaging during the first 30 days of life. Size of each temporal lobe infarction was estimated based on number of temporal lobe’s segments involved. Primary outcomes were presence of major neurodevelopmental impairments in childhood and Bayley scores at 2 years. RESULTS Our cohort of 19 infants had a median gestational age of 38 weeks [IQR 36–39] and mean birthweight 2892±920 grams. The most common presenting symptoms of VOL thrombosis and infarction of surrounding tissue were seizures, apnea, lethargy and either hyper- or hypotonia. At the latest clinical follow-up appointment documented in the electronic medical record (mean 4.4±3.08 years), 44% had major neurodevelopmental impairment. Patients with large VOL infarctions had significantly worse average Bayley scores than those with small to moderate lesions, differences in language composite were statistically significant (72.7 vs 107.8, p = 0.017). CONCLUSIONS Neonates with large VOL infarctions are more likely to have poor language outcomes. This suggests a need for targeted surveillance to ensure early identification of deficits and referral for intervention.
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