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Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence‐based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta‐analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non‐randomised studies ‐ of interventions (ROBINS‐I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first‐line ASM (evidence‐based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first‐line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second‐line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second‐line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal‐onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic–ischemic encephalopathy (evidence‐based recommendation). Fifth, treating neonatal seizures (including electrographic‐only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6‐dependent epilepsy and seizures unresponsive to second‐line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options. [ABSTRACT FROM AUTHOR]

Clinical recognition has been the cornerstone of the diagnosis and management of neonatal seizures from the earliest days of care for affected infants, and previous classification systems have been based on these bedside observations. Recently, the Task Force on Neonatal Seizures of the International League Against Epilepsy (ILAE) published a new classification system that has significant implications for the care of newborns suspected of seizures. This new construct includes electroencephalographic (EEG) confirmation rather than reliance solely on clinical observation of seizures.1 For some newborns, it will improve diagnosis and management that may affect long-term neurodevelopmental outcomes. For others, it may emphasize additional disparities in health care requiring new clinical strategies. Here, we discuss the rationale for the development of this new classification, advantages and limitations, potential impact, and new strategies for resource-challenged care centers. [ABSTRACT FROM AUTHOR]

Today, in NICUs all over the world, seizure treatment is started only when there is a strong clinical suspicion of seizures and/or there is confirmatory aEEG/cEEG evidence. Keywords: clinical trials; drug development; hypoxic-ischemic encephalopathy; seizures in newborns; treatment EN clinical trials drug development hypoxic-ischemic encephalopathy seizures in newborns treatment 1874 1879 6 07/15/22 20220701 NES 220701 INTRODUCTION Seizures present both diagnostic and therapeutic challenges in neonates who are admitted to neonatal intensive care units (NICUs) worldwide. Of course there is variability, as seizure onset depends on the time of occurrence of the primary injury.18 Seizures in HIE have a typical evolution, with a peak in seizure burden within the first 30 hours. Amplitude integrated EEG (aEEG) is more widely available for clinical management, but 20%-40% of seizures will be missed, in addition to a significant risk of false-positive detections.12 aEEG is not recommended for clinical trials of neonatal seizure treatment.13 WHAT DO WE KNOW ABOUT SEIZURES IN HIE?. [Extracted from the article]

Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group. [ABSTRACT FROM AUTHOR]

Background and purpose: Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy. Methods: A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement. Results: A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ‐aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted. Conclusions: These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug‐related adverse events in individuals living with PMD‐related epilepsy. [ABSTRACT FROM AUTHOR]

To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1–20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1–7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4–103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8–41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7–52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97–20.5, p = 0.002) Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: • Patients on ECMO are at a higher risk of seiures. • Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: • In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. • Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? • This study reports a 33% incidence of neonatal seizures during ECMO. • Neonates with seizures were 11 times more likely to have an abnormal brain scan. • The study captures the real-time approach of EEG monitoring. • Recommended cEEG monitoring should last at least 24 h for ECMO patients. • This is the first study to assess this in neonates only. [ABSTRACT FROM AUTHOR]

In contrast to epilepsy in adolescents and adults, neonatal seizures and early onset epilepsy poses unique challenges with significant repercussion for treatment choices. Most importantly, high seizure burden and epileptic encephalopathy are associated with developmental, behavioural and cognitive problems. The causes are multifactorial and include etiology, seizure burden, epileptic encephalopathy, but also antiseizure medication. In contrast to adults and older children only very few drugs have been licenced for infants and neonates, and after a long delay. Very recently, extrapolation of adult data has become possible as a path to speed up drug development for younger children but this is not necessarily possible for infants and neonates. With the advances in understanding the molecular basis of many epilepsies, targeted therapies become available, for example for KCNQ2 mutation related epilepsies, Dravet syndrome or tuberous sclerosis complex. Drug trials in neonates are particularly challenging because of their inconspicuous clinical presentation, the need for continuous EEG monitoring, high co-morbidity, and poor response to antiepileptic drugs. There is an urgent need for development of new drugs, evaluation of safety and efficacy of current antiseizure drugs, as well as for national policies and guidelines for the management of seizures and epilepsy in neonates and infants. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century – From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'. • Treatment of early onset seizures and epilepsies pose a clinical challenge to clinicians. • Only very few drugs have been licenced due to lack of randomised controlled trials. • Systematic reviews no good evidence for the choice of treatment. • Precision medicine is so far only available for a small number of syndromes. [ABSTRACT FROM AUTHOR]

Objective: Stereoelectroencephalography (SEEG) is being used more frequently in the pre‐surgical evaluation of children with focal epilepsy. It has been shown to be safe in children, but there are no multicenter studies assessing the rates and factors associated with the identification of a putative seizure‐onset zone (SOZ) and subsequent seizure freedom following SEEG‐guided epilepsy surgery. Methods: Multicenter retrospective cohort study of all children undergoing SEEG at six of seven UK Children's Epilepsy Surgery Service centers from 2014 to 2019. Demographics, noninvasive evaluation, SEEG, and operative factors were analyzed to identify variables associated with the identification of a putative SOZ and subsequent seizure freedom following SEEG‐guided epilepsy surgery. Results: One hundred thirty‐five patients underwent 139 SEEG explorations using a total of 1767 electrodes. A putative SOZ was identified in 117 patients (85.7%); odds of successfully finding an SOZ were 6.4 times greater for non‐motor seizures compared to motor seizures (p = 0.02) and 3.6 times more if four or more seizures were recorded during SEEG (p = 0.03). Of 100 patients undergoing surgical treatment, 47 (47.0%) had an Engel class I outcome at a median follow‐up of 1.3 years; the only factor associated with outcome was indication for SEEG (p = 0.03); an indication of "recurrence following surgery/treatment" had a 5.9 times lower odds of achieving seizure freedom (p = 0.002) compared to the "lesion negative" cohort, whereas other indications ("lesion positive, define extent," "lesion positive, discordant noninvasive investigations" and "multiple lesions") were not statistically significantly different. Significance: This large nationally representative cohort illustrates that SEEG‐guided surgery can still achieve high rates of seizure freedom. Seizure semiology and the number of seizures recorded during SEEG are important factors in the identification of a putative SOZ, and the indication for SEEG is an important factor in postoperative outcomes. [ABSTRACT FROM AUTHOR]

Objective To investigate the seizure response rate to lidocaine in a large cohort of infants who received lidocaine as second- or third-line antiepileptic drug ( AED) for neonatal seizures. Methods Full-term (n = 319) and preterm (n = 94) infants, who received lidocaine for neonatal seizures confirmed on amplitude-integrated EEG (aEEG), were studied retrospectively (January 1992-December 2012). Based on aEEG findings, the response was defined as good (>4 h no seizures, no need for rescue medication); intermediate (0-2 h no seizures, but rescue medication needed after 2-4 h); or no clear response (rescue medication needed <2 h). Results Lidocaine had a good or intermediate effect in 71.4%. The response rate was significantly lower in preterm (55.3%) than in full-term infants (76.1%, p < 0.001). In full-term infants the response to lidocaine was significantly better than midazolam as second-line AED (21.4% vs. 12.7%, p = 0.049), and there was a trend for a higher response rate as third-line AED (67.6% vs. 57%, p = 0.086). Both lidocaine and midazolam had a higher response rate as third-line AED than as second-line AED (p < 0.001). Factors associated with a good response to lidocaine were the following: higher gestational age, longer time between start of first seizure and administration of lidocaine, lidocaine as third-line AED, use of new lidocaine regimens, diagnosis of stroke, use of digital aEEG, and hypothermia. Multivariable analysis of seizure response to lidocaine included lidocaine as second- or third-line AED and seizure etiology. Significance Seizure response to lidocaine was seen in ~70%. The response rate was influenced by gestational age, underlying etiology, and timing of administration. Lidocaine had a significantly higher response rate than midazolam as second-line AED, and there was a trend for a higher response rate as third-line AED. Both lidocaine and midazolam had a higher response rate as third-line compared to second-line AED, which could be due to a pharmacologic synergistic mechanism between the two drugs. [ABSTRACT FROM AUTHOR]

The diagnosis of nonconvulsive status epilepticus ( NCSE) relies largely on electroencephalography ( EEG) findings. The lack of a unified EEG terminology, and of evidence-based EEG criteria, leads to varying criteria for and ability to diagnose NCSE. We propose a unified terminology and classification system for NCSE, using, as a template, the Standardised Computer-based Organised Reporting of EEG ( SCORE). This approach integrates the terminology recently proposed for the rhythmic and periodic patterns in critically ill patients, the electroclinical classification of NCSE (type of NCSE) and the context for the pathologic conditions and age-related epilepsy syndromes. We propose flexible EEG criteria that employ the SCORE system to assemble a database for determining evidence-based EEG criteria for NCSE. [ABSTRACT FROM AUTHOR]