Eilon Shany

Neonatal Seizures: Dilemmas in Workup and Management

There is a pressing need for consistent, evidence-based guidelines in the management of neonatal seizures by pediatric neurologists and neonatologists. Israeli pediatric neurologists and neonatologists completed a 20-item, self-administered questionnaire on choices of antiepileptic drugs, treatment of intractable neonatal seizures (unremitting seizures after 3 medications), treatment duration, and recommended workup. The responding 36/55 (65%) neurologists and 66/112 (59%) neonatologists made similar antiepileptic drug choices (phenobarbital as first line, phenytoin as second line, and benzodiazepines as third line). Antiepileptic treatment duration was similar for both groups, but varied considerably within them (range, 1-52 weeks). Neurologists tended to recommend longer treatment for seizures secondary to asphyxia or hemorrhage. Neurologists and neonatologists recommended different antiepileptic drugs for intractable neonatal seizures: valproic acid and topiramate by neurologists, vs lidocaine and benzodiazepines by neonatologists (P = 0.0023). Fewer neurologists recommended continuous electroencephalography monitoring after asphyxia than neonatologists (40% vs 70.5%, P = 0.013). These responses reflect both similarities and inconsistencies of the two groups in diagnosing and treating neonatal seizures. Our findings call for controlled clinical trials to establish protocols for (1) diagnosing neonatal seizures, (2) studying the efficacy and safety of new-generation antiepileptic drugs, and (3) determining optimal duration of drug administration.

Comparison of Continuous Drip of Midazolam or Lidocaine in the Treatment of Intractable Neonatal Seizures

Seizures constitute the most common neurological symptom in the neonatal period. Treatment usually involves the administration of intravenous benzodiazepines followed by either phenobarbital or phenytoin. For nonresponsive cases, continuous intravenous drip of either midazolam or lidocaine has been suggested for seizure control. Some reports suggest that seizures themselves may have a deleterious effect on long-term neurological outcome. Therefore, there is a need to find treatment regimens with better efficacy to provide maximum seizure control. The authors compared the effectiveness of lidocaine and midazolam in the treatment of intractable seizures in newborn infants born at or after 36 weeks of gestation who suffered from hypoxic-ischemic encephalopathy and who had their cerebral activity monitored. Thirty infants were included in the study: 22 received lidocaine, and 8 received midazolam. Seventeen (77%) infants had a good or partial response to lidocaine, and 4 (50%) had a partial response to midazolam. Of 20 infants diagnosed with hypoxic-ischemic encephalopathy grade 2, 18 (90%) responded to second-line treatment (14 [93%] of 15 to lidocaine and 4 [80%] of 5 to midazolam). Among 10 infants with hypoxic-ischemic encephalopathy grade 3, only 3 (30%) responded to second-line treatment (all 3 to lidocaine, none to midazolam). The findings suggest that lidocaine may be more effective than midazolam in reducing or controlling refractory neonatal seizures. The lower response rate to midazolam was more evident in infants with severe hypoxic-ischemic encephalopathy (grade 3).

Neonatal seizure recognition – Comparative study of continuous-amplitude integrated EEG versus short conventional EEG recordings

OBJECTIVES This study aims to detect seizures by amplitude-integrated electroencephalography (EEG) (aEEG) as compared with conventional EEG (cEEG) by clinicians with different levels of expertise. METHODS Simultaneous 10 min aEEG/cEEG recordings were time-locked and assessed for seizure activity. aEEG was assessed by a neonatologist, a fellow and a medical student and cEEG by two child neurologists and a neonatologist. RESULTS A total of 265 paired epochs from 38 simultaneous recording were assessed. Forty-one seizure episodes were diagnosed in 31 epochs in the cEEG recordings of 10 infants. Sensitivity and specificity ranged from 68% to 84% and from 71% to 84%, respectively, per detection of epochs with seizures and from 71% to 84% and from 36% to 96% per detection of individual seizures. No agreement was found between the observations of the student, and those of the fellow or neonatologist. Substantial agreement was found between the fellow and neonatologist. Before cEEG was commenced, seizures were detected by aEEG in 22 infants. CONCLUSIONS aEEG has high sensitivity and specificity in the hands of experienced users. Inexperienced new users may have a high rate of misdiagnosed seizures. Early recording of high-risk infants can help in the early diagnosis and treatment of seizures. SIGNIFICANCE Diagnosis and treatment of seizures in aEEG should be carried out by experienced users and should be supplemented with cEEG when available.

Influence of Antiepileptic Drugs on Amplitude-Integrated Electroencephalography

Amplitude-integrated electroencephalography monitors different aspects of cerebral function in neonatal intensive care units. To examine the influence of various antiepileptic drugs on the background patterns and voltage of amplitude-integrated electroencephalography recordings, we screened 191 tracing segments originating from 77 newborns treated with antiepileptic drugs. The influences of lorazepam, diazepam, and phenobarbital given as bolus doses, and midazolam and lidocaine given in continuous infusion, were examined. Voltages and patterns before and after drug administration were assessed. Time taken to return to previous voltage was assessed in clinically significant cases. Chi-square and Wilcoxon tests were used for statistical analyses. Significant changes were evident after lorazepam, diazepam, phenobarbital, and midazolam administration. Depending on the voltage-assessment method, a clinically significant depression of the lower voltage border occurred in 25-35% of tracings, and of the upper border in 16-32%. In 12% of tracings, change to a worse pattern was noted. The average time for recovery to predrug administration voltage was 2.5 hours (range, 15 minutes to 15 hours). Changes in amplitude-integrated electroencephalography tracings occur after antiepileptic drugs are infused. These changes include deterioration of pattern and depression of voltage that may persist for a considerable period. The potential depressing effects of these drugs should be taken into consideration when assessing amplitude-integrated electroencephalogram tracings.

Amplitude-Integrated Electroencephalography in Newborns with Inborn Errors of Metabolism

Background: The utility of amplitude-integrated electroencephalography (aEEG) monitoring has been established for patients with neonatal hypoxic-ischemic encephalopathy. Objective: To evaluate the role of aEEG in the diagnostic process and treatment of patients with encephalopathy due to inborn errors of metabolism. Methods: Cases collected through an international registry were divided into 5 groups of metabolic disorders. Common aEEG features were sought for each group. Results: In total, 21/30 (70%) cases had abnormal aEEG background patterns, 18/30 (60%) showed seizure activity. Patients with disorders of energy metabolism, hyperammonemia, and organic/amino acidopathies often showed marked aEEG depression with seizure activity. In contrast, aEEGs of patients with peroxisomal disorders did not show major background abnormalities but seizures were present in 5/6 subjects. We report two features of interest: firstly, two tracings displayed an unusual upward shift of the lower aEEG amplitude margin. Secondly, aEEGs of infants with non-ketotic hyperglycinemia showed a pattern we refer to as ‘high-frequency burst-suppression pattern’. Conclusions: aEEG in patients with inborn errors of metabolism frequently reveals abnormalities and assists clinicians in the clinical assessment, management and monitoring of these patients.

Increased risk for respiratory syncytial virus-associated, community-acquired alveolar pneumonia in infants born at 31-36 weeks of gestation.

Background: We compared hospitalization and pediatric intensive care unit (PICU) admission rates for community-acquired alveolar pneumonia (CAAP) and respiratory syncytial virus (RSV)-associated CAAP (RSV-CAAP) in non-RSV–immunized children <24-month-old born at 31–36 weeks gestational age (GA) versus those born at term (>36 weeks GA). Methods: Nasopharyngeal samples for RSV were obtained prospectively (2004–2011) during RSV season, from hospitalized children with radiographic-diagnosed CAAP. Soroka University Medical Center is the only hospital in the region, enabling population-based rate calculation. Relative risks (RR) and 95% confidence intervals (95% CI) were calculated comparing RSV-CAAP incidence in 31–36 weeks GA with >36 weeks GA children. Results: CAAP hospitalization incidences (per 1000 population) were 23.6 and 9.4 (RR: 2.52; 95% CI: 2.13–2.68), respectively; the respective incidences of PICU admission for overall CAAP were 1.8 and 0.2 (RR: 7.88; 95% CI: 4.59–11.83). The RRs (and 95% CI) for RSV-CAAP hospitalizations and PICU admission rates were (after extrapolation) 15.2 and 5.8 (RR: 2.79; 95% CI: 2.31–3.06) and 1.1 and 0.1 (RR: 9.14; 95% CI: 4.93–16.96), respectively. In a multiregression analysis in patients with RSV-CAAP versus CAAP, 31–36 weeks GA was an independent risk factor for hospitalization (RR: 1.485; 95% CI: 1.03–2.14). Conclusions: Children <24-month-old born at 31–36 weeks GA are at increased risk for hospitalization and PICU admission for both overall CAAP and RSV-associated CAAP compared with those born at >36 weeks GA. Moreover, in late premature children, RSV represented a 50% increased risk for CAAP compared with infants born at term.

A prospective study of the patterns and dynamics of colonization with Candida spp. in very low birth weight neonates

Abstract Background: Knowledge of fungal colonization patterns in very low birth weight infants (VLBWI) admitted to the neonatal intensive care unit (NICU) is essential in understanding the process of fungal infections in neonates. We analyzed prospectively, during 2009–2010, the patterns and dynamics of fungal colonization in VLBWI, including timing, colonization sites, and species involved. Methods: Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis. Results: Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed < 1000 g; 68 were delivered by cesarean section. Candida albicans (57/104, 55%) and Candida parapsilosis (26/104, 25%) were the main fungi isolated. Eight (24%) VLBWI were colonized during the first week and 23 (68%) during the second week. No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI. The colonization risk at least once during the first 10 weeks was 23% for skin, 14% for oropharynx, 27% for rectum/stool, and 38% for any anatomic site sampled. Persistent colonization was recorded in 5/34 (15%), while transient colonization was found in 14/34 (41%) VLBWI; 16/34 (47%) were discharged or died colonized with Candida spp. Candidemia was diagnosed in 4 (3%) VLBWI and previous/simultaneous colonization was found in 3/4. Conclusions: The cumulative risk of colonization, at any sampled site and at least once during follow-up, was high. Initial colonization occurred most often during the first 2 weeks of life. Colonization dynamics were characterized by various persistence, disappearance, and recolonization patterns. Candidemia was rare.

Neonatal Electroencephalography: Review of a Practical Approach

Neonatal electroencephalography (EEG) recordings have routinely been performed for more than half a century. ‘‘Old’’ technical difficulties are no longer of concern with the advent of modern digital technology. Still, many ‘‘old’’ issues are at debate: characterization of neonatal EEG features, identification of EEG waveforms with potential clinical correlates, the role of neonatal EEG in prediction of neurodevelopmental outcome, and use of new devices. In the past decades, neonatal EEG and emerging issues’ literature has greatly expanded. In this review, the authors have summarized some of these issues to increase the availability of the information for both clinical and research purposes. They propose an up-to-date concentrated practical approach to this rapidly expanding ‘‘subfield’’ of neonatal neurology.

Electroencephalographic Activity in Response to Procedural Pain in Preterm Infants Born at 28 and 33 Weeks Gestational Age

Objectives:Preterm infants undergo frequent painful procedures in the neonatal intensive care unit. Electroencephalography (EEG) changes in reaction to invasive procedures have been reported in preterm and full-term neonates. Frontal EEG asymmetry as an index of emotion during tactile stimulation shows inconsistent findings in full-term infants, and has not been examined in the context of pain in preterm infants. Our aim was to examine whether heel lance for blood collection induces changes in right-left frontal asymmetry, suggesting negative emotional response, in preterm neonates at different gestational age (GA) at birth and different duration of stay in the neonatal intensive care unit. Materials and Methods:Three groups of preterm infants were compared: set 1: group 1 (n=24), born and tested at 28 weeks GA; group 2 (n=22), born at 28 weeks GA and tested at 33 weeks; set 2: group 3 (n=25), born and tested at 33 weeks GA. EEG power was calculated for 30-second artifact-free periods, in standard frequency bandwidths, in 3 phases (baseline, up to 5 min after heel lance, 10 min after heel lance). Results:No significant differences were found in right-left frontal asymmetry, or in ipsilateral or contralateral somatosensory response, across phases. In contrast, the Behavioral Indicators of Infant Pain scores changed across phase (P<0.0001). Infants in group 1 showed lower Behavioral Indicators of Infant Pain scores (P=0.039). Discussion:There are technical challenges in recording EEG during procedures, as pain induces motor movements. More research is needed to determine the most sensitive approach to measure EEG signals within the context of pain in infancy.

Neonatal nosocomial pneumococcal infections acquired by patient-to-patient transmission.

A case of neonatal nosocomial pneumococcal sepsis acquired by patient-to-patient transmission and confirmed by phenotypic and genotypic typing is documented. To the best of our knowledge this is the first documented case of neonatal nosocomial person-to-person transmission.