High Effectiveness of Midazolam and Lidocaine in the Treatment of Acute Neonatal Seizures.

PURPOSE: To assess the clinical effectiveness of treating acute seizures with midazolam and lidocaine infusion. METHODS: This single-center historical cohort study included 39 term neonates with electrographic seizures who underwent treatment with midazolam (1st line) and lidocaine (2nd line). Therapeutic response was measured using continuous video-EEG monitoring. The EEG measurements included total seizure burden (minutes), maximum ictal fraction (minutes/hour), and EEG-background (normal/slightly abnormal vs. abnormal). Treatment response was considered good (seizure control with midazolam infusion), intermediate (need to add lidocaine to the control), or no response. Using clinical assessments supplemented by BSID-III and/or ASQ-3 at 2 to 9 years old age, neurodevelopment was classified as normal, borderline, or abnormal. RESULTS: A good therapeutic response was obtained in 24 neonates, an intermediate response in 15, and no response in any of the neonates. Babies with good response showed lower values in maximum ictal fraction compared with those with intermediate response (95% CI: 5.85-8.64 vs. 9.14-19.14, P = 0.002). Neurodevelopment was considered normal in 24 children, borderline in five, and abnormal in other 10 children. Abnormal neurodevelopment was significantly associated with an abnormal EEG background, maximum ictal fraction >11 minutes, and total seizure burden >25 minutes (odds ratio 95% CI: 4.74-1708.52, P = 0.003; 1.72-200, P = 0.016; 1.72-142.86, P = 0.026, respectively) but not with the therapeutic response. Serious adverse effects were not recorded. CONCLUSIONS: This retrospective study suggests that the midazolam/lidocaine association could potentially be efficacious in decreasing seizure burden in term neonates with acute seizures. These results would justify testing the midazolam/lidocaine combination as a first-line treatment for neonatal seizures in future clinical trials.

Assessment of neonatal EEG background and neurodevelopment in full-term small for their gestational age infants.

BACKGROUND: Delayed brain function development in small-gestational-age (SGA) infants has been reported. We aimed to quantify rates of immature neonatal EEG patterns and their association with neurodevelopment in SGA full-term neonates. METHODS: Using a cohort design, 50 SGA (birthweight <10th percentile) and 44 appropriate-gestational-age (AGA) term neonates underwent continuous video-EEG recordings lasting >3 h. Seventy-three of them were assessed at 2-years-old using Bayley-III-Scales. For EEG analysis, several segments of discontinuous/alternating EEG tracings were selected. MAIN OUTCOMES MEASURED: (1) Visual analysis (patterns of EEG maturity); (2) Power spectrum in δ, θ, α and ß frequency bands; and (3) scores in motor, cognitive and language development. RESULTS: (1) SGA infants, compared to AGA, showed: (a) higher percentages of discontinuous EEG, both asynchrony and interhemispheric asymmetry, and bursts with delta-brushes, longer interburst-interval duration and more transients/hour; (b) lower relative power spectrum in δ and higher in α; and (c) lower scores on motor, language and cognitive neurodevelopment. (2) Asymmetry >5%, interburst-interval >5 s, discontinuity >11%, and bursts with delta-brushes >11% were associated with lower scores on Bayley-III. CONCLUSIONS: In this prospective study, SGA full-term neonates showed high rates of immature EEG patterns. Low-birthweight and immaturity EEG were both correlated with low development scores.

Visual and Quantitative Electroencephalographic Analysis in Healthy Term Neonates Within the First Six Hours and the Third Day of Life.

BACKGROUND: What constitutes a "normal" background electroencephalography (EEG) rhythm immediately after birth is not well understood. We performed video-electroencephalography recordings in the first six hours (first measure) and the third day of life (second measure) for evidence of transient changes in brain function. METHODS: We performed a cohort study of an incidental sample of healthy term neonates in a single-center nursery. Main outcome measures were as follows: (1) EEG visual analysis, which included sleep-wake cycles, proportions of discontinuity and bursts with delta brushes, and number per hour of alpha/theta rolandic activity, encoches frontales, and transients; and (2) the electroencephalographic spectral analysis, which included power spectrum in the following frequency bands: delta, 0.5 to 4 Hz; theta, 4 to 8 Hz; alpha, 8 to 13 Hz; and beta, 13 to 30 Hz. Theta/delta and alpha/delta ratios were also calculated. RESULTS: Twenty-two babies were enrolled. Significant findings (P < 0.05) in the first six hours with respect to 48 to 72 hours of life were (1) increased discontinuity, indeterminate sleep, and bursts with delta brushes; (2) higher number of transients, and lower number of alpha/theta rolandic activity and encoches frontales. Minimal changes were found in power spectrum data. However, using receiver operating characteristic curve analysis, theta/delta ratio ≤0.484 was the best cutoff to discriminate between the two measures (positive predictive value, 100.0; 95% confidence interval 71.0 to 100). CONCLUSIONS: In healthy term neonates, immature electroencephalographic patterns, lack of clearly defined sleep-wake cycles, and frequent transients can be considered normal electroencephalographic findings in the first six hours of life. Normative power spectrum data are provided. These findings suggest that neonatal adaptation immediately after birth leads to transient changes in brain function.

Video-EEG recordings in full-term neonates of diabetic mothers: observational study.

OBJECTIVE: To determine whether full-term newborn infants of diabetic mothers (IDM) present immature/disorganised EEG patterns in the immediate neonatal period, and whether there was any relationship with maternal glycaemic control. DESIGN AND SETTING: Cohort study with an incidental sample performed in a tertiary hospital neonatal unit. PATIENTS: 23 IDM and 22 healthy newborns born between 2010 and 2013. INTERVENTIONS: All underwent video-EEG recording lasting >90 min at 48-72 h of life. MAIN OUTCOME MEASURES: We analysed the percentage of indeterminate sleep, transient sharp waves per hour and mature-for-gestational age EEG patterns (discontinuity, maximum duration of interburst interval (IBI), asynchrony, asymmetry, δ brushes, encoches frontales and α/θ rolandic activity). The group of IDM was divided into two subgroups according to maternal HbA1c: (1) HbA1c≥6% and (2) HbA1c<6%. RESULTS: Compared with healthy newborns, IDM presented significantly higher percentage of indeterminate sleep (57% vs 25%; p<0.001), discontinuity (2.5% vs 0%; p=0.044) and δ brushes in the bursts (6% vs 3%; p=0.024); higher duration of IBI (0.3 s vs 0 s; p=0.017); fewer encoches frontales (7/h vs 35/h; p<0.001), reduced θ/α rolandic activity (3/h vs 9/h; p<0.001); and more transient sharp waves (25/h vs 5/h; p<0.001). IDM with maternal HbA1c≥6% showed greater percentage of δ brushes in the burst (14% vs 4%; p=0.007). CONCLUSIONS: Full-term IDM newborns showed video-EEG features of abnormal development of brain function. Maternal HbA1c levels<6% during pregnancy could minimise the risk of cerebral dysmaturity.

Neonatal apneic seizure of occipital lobe origin: continuous video-EEG recording.

We present 2 term newborn infants with apneic seizure originating in the occipital lobe that was diagnosed by video-EEG. One infant had ischemic infarction in the distribution of the posterior cerebral artery, extending to the cingulate gyrus. In the other infant, only transient occipital hyperechogenicity was observed by using neurosonography. In both cases, although the critical EEG discharge was observed at the occipital level, the infants presented no clinical manifestations. In patient 1, the discharge extended to the temporal lobe first, with subtle motor manifestations and tachycardia, then synchronously to both hemispheres (with bradypnea/hypopnea), and the background EEG activity became suppressed, at which point the infant experienced apnea. In patient 2, background EEG activity became suppressed right at the end of the focal discharge, coinciding with the appearance of apnea. In neither case did the clinical description by observers coincide with video-EEG findings. The existence of connections between the posterior limbic cortex and the temporal lobe and midbrain respiratory centers may explain the clinical symptoms recorded in these 2 cases. The novel features reported here include video-EEG capture of apneic seizure, ischemic lesion in the territory of the posterior cerebral artery as the cause of apneic seizure, and the appearance of apnea when the epileptiform ictal discharge extended to other cerebral areas or when EEG activity became suppressed. To date, none of these clinical findings have been previously reported. We believe this pathology may in fact be fairly common, but that video-EEG monitoring is essential for diagnosis.