Amplitude-Integrated Electroencephalography for Early Recognition of Brain Injury in Neonates with Critical Congenital Heart Disease.

OBJECTIVE: To study perioperative amplitude-integrated electroencephalography (aEEG) as an early marker for new brain injury in neonates requiring cardiac surgery for critical congenital heart disease (CHD). STUDY DESIGN: This retrospective observational cohort study investigated 76 neonates with critical CHD who underwent neonatal surgery. Perioperative aEEG recordings were evaluated for background pattern (BGP), sleep-wake cycling (SWC), and ictal discharges. Spontaneous activity transient (SAT) rate, inter-SAT interval (ISI), and percentage of time with an amplitude <5 µV were calculated. Routinely obtained preoperative and postoperative magnetic resonance imaging of the brain were reviewed for brain injury (moderate-severe white matter injury, stroke, intraparenchymal hemorrhage, or cerebral sinovenous thrombosis). RESULTS: Preoperatively, none of the neonates showed an abnormal BGP (burst suppression or worse) or ictal discharges. Postoperatively, abnormal BGP was seen in 18 neonates (24%; 95% CI, 14%-33%) and ictal discharges was seen in 13 neonates (17%; 95% CI, 8%-26%). Abnormal BGP and ictal discharges were more frequent in neonates with new postoperative brain injury (P = .08 and .01, respectively). Abnormal brain activity (ie, abnormal BGP or ictal discharges) was the single risk factor associated with new postoperative brain injury in multivariable logistic regression analysis (OR, 4.0; 95% CI, 1.3-12.3; P = .02). Postoperative SAT rate, ISI, or time <5 µV were not associated with new brain injury. CONCLUSION: Abnormal brain activity is an early, bedside marker of new brain injury in neonates undergoing cardiac surgery. Not only ictal discharges, but also abnormal BGP, should be considered a clear sign of underlying brain pathology.

Clinical characteristics and diagnoses of 1213 children referred to a first seizure clinic.

OBJECTIVE: New-onset seizure-like events (SLEs) are common in children, but differentiating between epilepsy and its mimics is challenging. This study provides an overview of the clinical characteristics, diagnoses, and corresponding etiologies of children evaluated at a first seizure clinic (FSC), which will be helpful for all physicians involved in the care of children with SLEs. METHODS: We included 1213 children who were referred to the FSC of a Dutch tertiary children's hospital over a 13-year period and described their clinical characteristics, first routine EEG recording results, and the distribution and specification of their eventual epilepsy and non-epilepsy diagnoses. The time interval to correct diagnosis and the diagnostic accuracy of the FSC were evaluated. RESULTS: "Epilepsy" was eventually diagnosed in 407 children (33.5%), "no epilepsy" in 737 (60.8%), and the diagnosis remained "unclear" in 69 (5.7%). Epileptiform abnormalities were seen in 60.9% of the EEG recordings in the "epilepsy" group, and in 5.7% and 11.6% of the "no epilepsy" and "unclear" group, respectively. Of all children with final "epilepsy" and "no epilepsy" diagnoses, 68.6% already received their diagnosis at FSC consultation, and 2.9% of the children were initially misdiagnosed. The mean time to final diagnosis was 2.0 months, and 91.3% of all children received their final diagnosis within 12 months after the FSC consultation. SIGNIFICANCE: We describe the largest pediatric FSC cohort to date, which can serve as a clinical frame of reference. The experience and expertise built at FSCs will improve and accelerate diagnosis in children with SLEs. PLAIN LANGUAGE SUMMARY: Many children experience events that resemble but not necessarily are seizures. Distinguishing between seizures and seizure mimics is important but challenging. Specialized first-seizure clinics can help with this. Here, we report data from 1213 children who were referred to the first seizure clinic of a Dutch children's hospital. One-third of them were diagnosed with epilepsy. In 68.8% of all children-with and without epilepsy-the diagnosis was made during the first consultation. Less than 3% were misdiagnosed. This study may help physicians in what to expect regarding the diagnoses in children who present with events that resemble seizures.

High-frequency oscillations in scalp EEG: A systematic review of methodological choices and clinical findings.

OBJECTIVE: Pathological high-frequency oscillations (HFOs) in intracranial EEG are promising biomarkers of epileptogenic tissue, and their physiological counterparts play a role in sensorimotor and cognitive function. HFOs have also been found in scalp EEG, but an overview of all studies is lacking. In this systematic review, we assessed the methodology to detect scalp HFOs and their clinical potential. METHODS: We searched PubMed, Embase and the Cochrane Library for studies on HFOs in scalp EEG, and extracted methodological and clinical data. RESULTS: We included 60 studies with data from 1149 unique individuals. Two-thirds of studies analyzed HFOs visually in the time or time-frequency domain, and one-third automatically with visual validation. Most studies evaluated interictal ripples during sleep in children. Pathological HFOs were overall better than spikes in localizing the epileptogenic zone and predicting outcome, correlated negatively with cognition and positively with disease activity and severity, and decreased after medical and surgical treatment. CONCLUSIONS: The methodologies of the 60 studies were heterogeneous, but pathological scalp HFOs were clinically valuable as biomarkers in various situations, particularly in children with epilepsy. SIGNIFICANCE: This systematic review gives an extensive overview of methodological and clinical data on scalp HFOs, establishing their clinical potential and discussing their limitations.

High-frequency oscillations recorded with surface EEG in neonates with seizures.

OBJECTIVE: Neonatal seizures are often the first symptom of perinatal brain injury. High-frequency oscillations (HFOs) are promising new biomarkers for epileptogenic tissue and can be found in intracranial and surface EEG. To date, we cannot reliably predict which neonates with seizures will develop childhood epilepsy. We questioned whether epileptic HFOs can be generated by the neonatal brain and potentially predict epilepsy. METHODS: We selected 24 surface EEGs sampled at 2048 Hz with 175 seizures from 16 neonates and visually reviewed them for HFOs. Interictal epochs were also reviewed. RESULTS: We found HFOs in thirteen seizures (7%) from four neonates (25%). 5025 ictal ripples (rate 10 to 1311/min; mean frequency 135 Hz; mean duration 66 ms) and 1427 fast ripples (rate 8 to 356/min; mean frequency 298 Hz; mean duration 25 ms) were marked. Two neonates (13%) showed interictal HFOs (285 ripples and 25 fast ripples). Almost all HFOs co-occurred with sharp transients. We could not find a relationship between neonatal HFOs and outcome yet. CONCLUSIONS: Neonatal HFOs co-occur with ictal and interictal sharp transients. SIGNIFICANCE: The neonatal brain can generate epileptic ripples and fast ripples, particularly during seizures, though their occurrence is not common and potential clinical value not evident yet.

Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies.

BACKGROUND & AIMS: Patients with malignant gliomas have a poor prognosis. Diets that lower blood glucose, such as ketogenic or caloric restricted diets (KCRDs), are hypothesized to reduce tumor growth and improve survival. In this systematic review, we summarize preclinical and clinical data on KCRDs in gliomas. METHODS: We searched PubMed and Embase for preclinical and clinical studies on KCRDs in gliomas, and extracted data on surrogate and clinically relevant endpoints, in accordance with PRISMA statement. Quality assessment of clinical studies was performed with use of Cochrane Collaboration's tool. We performed Fisher's exact test to examine associations between surrogate and clinically relevant endpoints. RESULTS: We included 24 preclinical studies, seven clinical studies and one mixed study. Both preclinical and clinical studies were highly heterogeneous. Preclinically, KCRDs reduced tumor growth, but only a small majority of the in vivo studies found improved survival. These effects were stronger in groups with decreased blood glucose than in those with increased ketones, and also when other therapies were used concomitantly. Finally, KCRDs influence multiple molecular-biological pathways, including the PTEN/Akt/TSC2 and NF-kB pathway. In clinical studies, KCRDs seem to be safe and feasible in glioma patients. Clinical data were insufficient to draw conclusions regarding efficacy. CONCLUSIONS: KCRDs have positive effects on malignant gliomas in published preclinical studies. Preliminary clinical data suggest that KCRDs are safe and feasible. However, because of the paucity of clinical data, the efficacy of KCRDs for improving survival and quality of life of glioma patients remains to be proven in prospective studies.