A Comparison of Treatment Practices for Newborn Seizure Management Across Level II and III Neonatal Intensive Care Units in the United States.

BACKGROUND: Neonatal seizures (NS) represent an important clinical manifestation among critically ill infants and are often the first sign of underlying brain injury. Early recognition and treatment are essential to reduce morbidity and mortality. The present study investigated the NS management and treatment approaches employed by level II/III neonatal intensive care units (NICUs) across the United States to identify areas of consensus and variability. METHODS: Personnel associated with level II/III NICUs were directly surveyed with an electronic questionnaire. Access to neurology specialists, on-site electroencephalography (EEG) monitoring, and use of antiseizure medications was directly queried. A total of 51 NICUs participated in this survey. RESULTS: Twenty-five percent of the surveyed NICUs reported having an established clinical practice pathway available for treating NS. Twenty-four percent endorsed having written guidelines that provided a formal definition for the concept of "neonatal seizures." Although the majority of NICUs reported having phenobarbital available for rapid seizure management, most NICUs lacked access to additional antiseizure medications for treatment escalation. Twenty-four percent of the surveyed NICUs had no access to EEG monitoring available to them on-site. Daytime and overnight access to neurology consultants was limited and variable. CONCLUSIONS: Findings were consistent with a lack of equitable access for NS treatment. Areas of potential improvement include development and implementation of a protocol for rapidly treating NS that emphasizes enhanced access to EEG and rapid neurology consultation, acknowledging and improving upon resource limitations. These developments may eventually provide earlier detection, evaluation, and treatment of seizures in newborns, contributing to improved long-term outcomes.

A single exposure to brivaracetam or perampanel does not cause cell death in neonatal rats.

Introduction: Exposure to a range of anti-seizure medications (ASMs) during early brain development adversely impacts neurodevelopmental outcomes in both animal models and in clinical studies. Many ASMs, including phenobarbital, phenytoin, valproate (VPA), and benzodiazepines, are associated with acute neurotoxicity (cell death), impaired synaptic development, and long-term behavioral changes following gestational or neonatal exposure in animals. This is mirrored in clinical studies which show lasting neurodevelopmental deficits following early-life or gestational exposure to these drugs. Brivaracetam (BRV) and perampanel (PER) are two newer generation anti-seizure medications and are of interest based on their mechanisms of action (SV2A modulator, AMPA antagonist, respectively), as other drugs with these mechanisms of action do not trigger acute neurotoxicity. Both BRV and PER show anti-seizure efficacy in developing animals, but potential neurotoxicity of these drugs is unexplored. Methods: To address this gap, we treated postnatal day (P)7 Sprague-Dawley rats with BRV (20, 40, 80 mg/kg) and PER (0.1, 0.9, 2.7 mg/kg), and assessed the induction of cell death across a range of vulnerable brain regions 24 h after exposure. Cell death was assessed using pathogreen staining. Results: In each of the regions examined (dorsal striatum, nucleus accumbens, motor cortex, cingulate cortex, lateral thalamus, septum, hippocampus), VPA, which served as a positive control, significantly increased cell death as measured by the numer of pathogreen positive cells. By contrast, neither BRV nor PER increased the number of pathogreen positive cells in any region examined. Discussion: Our results suggest that BRV and PER may have a positive safety profile-at least with respect to acute induction of cell death - and therefore may offer a safer option for the treatment of early life seizures.

Lacosamide Boluses Decreased Seizure Burden and Were Well Tolerated in Neonates With Acute Seizures: A Single-Center Retrospective Case Series.

Introduction: Neonatal seizures are associated with worsened neurodevelopmental outcomes. Phenobarbital, the only US Food and Drug Administration (FDA)-approved treatment for neonatal seizures, can cause neuronal apoptosis and may worsen neurodevelopmental outcomes. Lacosamide may be an efficacious treatment for neonatal seizures. Methods: We assessed the impact of lacosamide boluses on seizure burden in a retrospective cohort of 15 neonates monitored with video electroencephalography (EEG). Medication bolus times and seizure start/end times on EEG tracings determined change in seizure burden. Results: Seven patients received lacosamide as first- or second-line treatment and 8 as third-line or later. Average 4-hour seizure burden decreased from 13% to 3% following lacosamide boluses (P = .002). Reduction in seizure burden greater than 30% followed 79% of boluses. Lacosamide was well tolerated; one patient experienced mild asymptomatic episodic bradycardia that medication taper resolved. Conclusions: Lacosamide significantly decreased seizure burden in this cohort. Prospective studies of lacosamide treatment for neonatal seizures are warranted.

Functional analysis of a novel nonsense PPP1R12A variant in a Chinese family with infantile epilepsy.

BACKGROUND: Defects in PPP1R12A can lead to genitourinary and/or brain malformation syndrome (GUBS). GUBS is primarily characterized by neurological or genitourinary system abnormalities, but a few reported cases are associated with neonatal seizures. Here, we report a case of a female newborn with neonatal seizures caused by a novel variant in PPP1R12A, aiming to enhance the clinical and variant data of genetic factors related to epilepsy in early life. METHODS: Whole-exome and Sanger sequencing were used for familial variant assessment, and bioinformatics was employed to annotate the variant. A structural model of the mutant protein was simulated using molecular dynamics (MD), and the free binding energy between PPP1R12A and PPP1CB was analyzed. A mutant plasmid was constructed, and mutant protein expression was analyzed using western blotting (WB), and the interaction between the mutant and PPP1CB proteins using co-immunoprecipitation (Co-IP) experiments. RESULTS: The patient experienced tonic-clonic seizures on the second day after birth. Genetic testing revealed a heterozygous variant in PPP1R12A, NM_002480.3:c.2533 C > T (p.Arg845Ter). Both parents had the wild-type gene. MD suggested that loss of the C-terminal structure in the mutant protein altered its structural stability and increased the binding energy with PPP1CB, indicating unstable protein-protein interactions. On WB, a low-molecular-weight band was observed, indicating that the protein was truncated. Co-IP indicated that the mutant protein no longer interacted with PPP1CB, indicating an effect on the structural stability of the myosin phase complex. CONCLUSION: The PPP1R12A c.2533 C > T variant may explain the neonatal seizures in the present case. The findings of this study expand the spectrum of PPP1R12A variants and highlight the potential significance of truncated proteins in the pathogenesis of GUBS.

[Neonatal epileptics syndromes]. / Síndromes epilépticos neonatales.

Neonatal epileptic syndromes are part of the genetic and metabolic epilepsies in this age group. Although they are not the most frequent cause of neonatal seizures, their early recognition allows for better diagnostic and therapeutic approaches. These syndromes can be classified into self-limited neonatal syndromes and early infantile epileptic and developmental encephalopathies (EIDEE). While they may share semiology in some types of seizures, such as sequential, and even share alterations in common genes in their etiology, their evolution is very different. In self-limited neonatal syndromes, seizures typically resolve within the first months of life with normal psychomotor development, giving rise to the term self-limited. However, the term benign should not be used as some may present recurrence of seizures, movement disorders, or learning disorders. In the case of EIDEE, seizures are usually refractory to treatment, affecting brain functions and neurodevelopment. In this review, our aim was to describe the electroclinical phenotype of neonatal epileptic syndromes, the most frequently involved genes and their clinical spectrum, their diagnostic approach, as well as the recommended treatments.

Los síndromes epilépticos neonatales hacen parte de las epilepsias de origen genético y metabólico en este grupo edad y aunque no son la causa más frecuente de crisis neonatales, su reconocimiento temprano permite dirigir mejor su enfoque diagnóstico y tratamiento. Pueden clasificarse en síndromes neonatales autolimitados y encefalopatías epilépticas y del desarrollo infantil temprano (EIDEE). Aunque pueden mostrar semiología similar en algunos tipos de crisis, como las secuenciales, e incluso comparten alteraciones en genes comunes en su etiología, su evolución es muy diferente. En los síndromes autolimitados, las crisis remiten en los primeros meses de vida alcanzando un desarrollo psicomotor normal, lo que da su nombre de autolimitado; sin embargo, el término benigno no debe utilizarse dado que algunos pueden presentar recurrencia de crisis, trastornos del movimiento o trastornos del aprendizaje. En las EIDEE las crisis suelen ser refractarias al tratamiento y se comprometen funciones cerebrales y el neurodesarrollo. En esta revisión describiremos el fenotipo electroclínico de los síndromes epilépticos neonatales, los genes más frecuentemente involucrados y su espectro clínico, su enfoque diagnóstico, así como los tratamientos recomendados.

Sequential levetiracetam and phenytoin in electroencephalographic neonatal seizures unresponsive to phenobarbital: a multicenter prospective observational study in India.

Background: Although levetiracetam and phenytoin are widely used antiseizure medications (ASM) in neonates, their efficacy on seizure freedom is unclear. We evaluated electroencephalographic (EEG) seizure freedom following sequential levetiracetam and phenytoin in neonatal seizures unresponsive to phenobarbital. Methods: We recruited neonates born ≥35 weeks and aged <72 h who had continued electrographic seizures despite phenobarbital, from three Indian hospitals, between 20 June 2020 and 31 July 2022. The neonates were treated with intravenous levetiracetam (20 mg/kg x 2 doses, second line) followed by phenytoin (20 mg/kg x 2 doses, third line) if seizures persisted. The primary outcome was complete seizure freedom, defined as an absence of seizures on EEG for at least 60 min within 40 min from the start of infusion. Findings: Of the 206 neonates with continued seizures despite phenobarbital, 152 received levetiracetam with EEG. Of these one EEG was missing, 47 (31.1%) were in status epilepticus, and primary outcome data were available in 145. Seizure freedom occurred in 20 (13.8%; 95% CI 8.6%-20.5%) after levetiracetam; 16 (80.0%) responded to the first dose and 4 (20.0%) to the second dose. Of the 125 neonates with persisting seizures after levetiracetam, 114 received phenytoin under EEG monitoring. Of these, the primary outcome data were available in 104. Seizure freedom occurred in 59 (56.7%; 95% CI 46.7%-66.4%) neonates; 54 (91.5%) responded to the first dose and 5 (8.5%) to the second dose. Interpretation: With the conventional doses, levetiracetam was associated with immediate EEG seizure cessation in only 14% of phenobarbital unresponsive neonatal seizures. Additional treatment with phenytoin along with levetiracetam attained seizure freedom in further 57%. Safety and efficacy of higher doses of levetiracetam should be evaluated in well-designed randomised controlled trials. Funding: National Institute for Health and Care Research (NIHR) Research and Innovation for Global Health Transformation (NIHR200144).

Clinical Experience With Lacosamide as an Adjunct Treatment for Neonatal Seizures: A Retrospective Single-Center Study.

BACKGROUND: Lacosamide (LCM) is a third-generation antiseizure medication (ASM) currently approved for the treatment of focal seizures in children aged greater than one month. There are limited data on its efficacy in the neonatal age group. We describe our experience with LCM as an adjunct ASM for the treatment of neonatal seizures. METHODS: A retrospective chart review over a five-year period (2018 to 2022) was conducted at Le Bonheur Children's Hospital to identify neonates with electroencephalography (EEG)-proven seizures who were treated with LCM. Data were collected on electroclinical seizure characteristics, underlying etiology, ASMs, treatment response, and any adverse effects. RESULTS: A total of 15 neonates with EEG-confirmed seizures who were treated with LCM were included. Ten neonates achieved seizure cessation after LCM was added to their ASM regimen consisting of phenobarbital, levetiracetam, or both. No new treatment-related adverse effects were noted. CONCLUSIONS: LCM is effective as an adjunct treatment for neonatal seizures. Randomized controlled studies are needed to establish its effectiveness and adequate dosing regimen in this population.

Current Evidence: Seizures in Extremely Low Gestational Age Newborns (ELGANs).

Extremely low gestational age newborns (ELGANs) are born at or below 28 weeks of gestational age. Despite improved obstetric care, the incidence of preterm birth continues to rise in advanced countries. Preterm birth remains a major cause of infant mortality, and for infants who survive, neonatal seizures are a significant predictor of later neurologic morbidity. However, little is known about risk factors for neonatal seizures in ELGANs. Understanding the association between neonatal seizures and the development of other neurologic disorders is important given the increasing prevalence of ELGANs. Identifying risk factors that contribute to the development of neonatal seizures in ELGANs may offer insights into novel mechanisms of epileptogenesis in the developing brain and improvements in the prevention or treatment of seizures in preterm infants, including ELGANs. In this literature review, we outline the limitations of epidemiologic studies of neonatal seizures in ELGANs and discuss risk factors for neonatal seizures.

The clinical value of amplitude-integrated electroencephalography in a historical cohort with neonatal encephalopathy: A comparison of short-term versus prolonged-period monitoring.

BACKGROUND: To compare the amplitude-integrated electroencephalography (aEEG) monitoring (short-term versus prolonged-period) for neonatal seizure detection and outcome. METHODS: The aEEG monitoring in a historical cohort (n = 88, preterm:42, and term:46) with neonatal encephalopathy between 2010-2022 was re-evaluated for neonatal seizures (electrographic, electro-clinical, and clinical seizures) and EEG background scoring. The cohort was dichotomized: group I (short-period with 6-12 h, n = 36) and group II (prolonged-period with 24-48 h, n = 52). Both monitoring types were evaluated for the diagnostic accuracy of the "patients with seizures" and for outcome characteristics (early death as well as adverse outcomes at 12 months of age). RESULTS: A total of 67 (76 %) neonates of the cohort were diagnosed as "patients with seizures": electrographic-only seizures in 10 (15 %), electro-clinical seizures in 22 (33 %), and clinical-only seizures in 35 (52 %). The aEEG provides the "patients with seizures" in neonates with a 36.5 % rate with both types of monitoring: 17/36 (47.2 %) with short-term and 15/52 (28.8 %) with prolonged-period monitoring. The prolonged period aEEG had higher diagnostic values for seizure detection (sensitivity = 0.73 and negative predictivity value = 0.81). However, the aEEG background scores were similar for both types of aEEG monitoring, respectively (the mean ± SD: 4.73 ± 2.9 versus 4.4 ± 4. p = 0.837). The aEEG scoring was correlated with the magnitude of brain injury documented with MRI, the early death, and the adverse outcome at 12 months of age. CONCLUSIONS: Both aEEG types are valuable for monitoring the "patients with seizures" and outcome characteristics.

Incidence and predictors of neonatal seizures among neonates admitted in Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia. A prospective follow-up study.

Introduction: Neonatal seizures are the most common neurological problem among newborns. To date, scientific studies on the incidence and predictors of neonatal seizures in African countries, including Ethiopia are scarce. Therefore, this study aimed to assess the incidence and predictors of neonatal seizures among neonates admitted to Debre Markos comprehensive Specialized Hospital. Methods: An institutional-based prospective follow-up study was conducted in Debre Markos comprehensive specialized hospital from February 1, 2022 to January 30, 2023. A systematic random sampling technique was used to select a total of 198 neonates. Data were entered into Epi-Data 4.2 and then exported to STATA version 14.1 for analysis. The Kaplan-Meier survival curve and the log-rank test were computed to explore the descriptive statistics. Variables with a p-value ≤0.2 in bi-variable Cox-regression were selected for multivariable Cox-regression analysis. Finally, a p-value of <0.05 was used to declare the statistical significance of the association with the outcome variable. Results: The overall incidence rate of neonatal seizures was 35 per 1000 person-day observations. The mean follow-up time for this study was 123.4 h. The cumulative survival probability of neonates' at 0 to 24 and 0-72 h was 89.8 % and 81.71 %, respectively. The statistically significant predictors for the incidence of neonatal seizures were perinatal asphyxia (AHR = 10.95; 95%CI: 4.81, 24.93), subgaleal hemorrhage (AHR = 5.17; 95%CI: 2.09, 12.79), and gestational age <37 weeks (AHR = 4.62; 95%CI: 1.62, 13.22). Conclusions: The incidence rate of neonatal seizures in this study was high. Neonates born with gestational age <37 weeks, having perinatal asphyxia, and having subgaleal hemorrhage were statistical predictors for the incidence of neonatal seizures. Thus, healthcare professionals should give special attention to neonates born with gestational age <37 weeks, prevent perinatal asphyxia and subgaleal hemorrhage.

PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications.

BACKGROUND: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). MATERIALS AND METHODS: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. RESULTS: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. CONCLUSIONS: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine.

Identifying Metabolic Diseases That Precipitate Neonatal Seizures.

Although a rare cause of neonatal seizures, inborn errors of metabolism (IEMs) remain an essential component of a comprehensive differential diagnosis for poorly controlled neonatal epilepsy. Diagnosing neonatal-onset metabolic conditions proves a difficult task for clinicians; however, routine state newborn screening panels now include many IEMs. Three in particular-pyridoxine-dependent epilepsy, maple syrup urine disease, and Zellweger spectrum disorders-are highly associated with neonatal epilepsy and neurocognitive injury yet are often misdiagnosed. As research surrounding biomarkers for these conditions is emerging and gene sequencing technologies are advancing, clinicians are beginning to better establish early identification strategies for these diseases. In this literature review, the authors aim to present clinicians with an innovative clinical guide highlighting IEMs associated with neonatal-onset seizures, with the goal of promoting quality care and safety.

KCNQ2 mutations cause unique neonatal behavior arrests without motor seizures: Functional characterization.

OBJECTIVE: KCNQ2 gene mutation usually manifests as neonatal seizures in the first week of life. Nonsense mutations cause a unique self-limited familial neonatal epilepsy (SLFNE), which is radically different from developmental epileptic encephalopathy (DEE). However, the exact underlying mechanisms remain unclear. METHODS: The proband, along with their mother and grandmother, carried the c.1342C > T (p.Arg448Ter) mutation in the KCNQ2 gene. The clinical phenotypes, electroencephalography (EEG) findings, and neurodevelopmental outcomes were comprehensively surveyed. The mutant variants were transfected into HEK293 cells to investigate functional changes. RESULTS: The proband exhibited behavior arrests, autonomic and non-motor neonatal seizures with changes in heart rate and respiration. EEG exhibited focal sharp waves. Seizures were remitted after three months of age. The neurodevelopmental outcomes at three years of age were unremarkable. A functional study demonstrated that the currents of p.Arg448Ter were non-functional in homomeric p.Arg448Ter compared with that of the KCNQ2 wild type. However, the current density and V1/2 exhibited significant improvement and close to that of the wild-type after transfection with heteromeric KCNQ2 + p.Arg448Ter and KCNQ2 + KCNQ3 + p.Arg448Ter respectively. Channel expression on the cell membrane was not visible after homomeric transfection, but not after heteromeric transfection. Retigabine did not affect homomeric p.Arg448Ter but improved heteromeric p. Arg448Ter + KCNQ2 and heteromeric KCNQ2 + Arg448Ter + KCNQ3. CONCLUSIONS: The newborn carrying the p. Arg448Ter mutation presented frequent behavioral arrests, autonomic, and non-motor neonatal seizures. This unique pattern differs from KCNQ2 seizures, which typically manifest as motor seizures. Although p.Arg448Ter is a non-sense decay, the functional study demonstrated an almost-full compensation mechanism after transfection of heteromeric KCNQ2 and KCNQ3.

Neonatal morbidity and mortality in birth centers in the United States 2018-2021: An observational study of low-risk birthing individuals.

BACKGROUND: Many studies reporting neonatal outcomes in birth centers include births with risk factors not acceptable for birth center care using the evidence-based CABC criteria. Accurate comparisons of outcomes by birth setting for low-risk patients are needed. METHODS: Data from the public Natality Detailed File from 2018 to 2021 were used. Logistic regression, including adjusted and unadjusted odds ratios, compared neonatal outcomes (chorioamnionitis, Apgar scores, resuscitation, intensive care, seizures, and death) between centers and hospitals. Covariates included maternal diabetes, body mass index, age, parity, and demographic characteristics. RESULTS: The sample included 8,738,711 births (8,698,432 (99.53%) in hospitals and 40,279 (0.46%) in birth centers). There were no significant differences in neonatal deaths (aOR 1.037; 95% CI [0.515, 2.088]; p-value 0.918) or seizures (aOR 0.666; 95% CI [0.315, 1.411]; p-value 0.289). Measures of morbidity either not significantly different or less likely to occur in birth centers compared to hospitals included chorioamnionitis (aOR 0.032; 95% CI [0.020, 0.052]; p-value < 0.001), Apgar score < 4 (aOR 0.814, 95% CI [0.638, 1.039], p-value 0.099), Apgar score < 7 (aOR 1.075, 95% CI [0.979, 1.180], p-value 0.130), ventilation >6 h (aOR 0.349; [0.281,0.433], p-value < 0.001), and intensive care admission (aOR 0.356; 95% CI [0.328, 0.386], p-value < 0.001). Birth centers had higher odds of assisted neonatal ventilation for <6 h as compared to hospitals (aOR 1.373; 95% CI [1.293, 1.457], p-value < 0.001). CONCLUSION: Neonatal deaths and seizures were not significantly different between freestanding birth centers and hospitals. Chorioamnionitis, Apgar scores < 4, and intensive care admission were less likely to occur in birth centers.

D-Bifunctional Protein Deficiency Diagnosis-A Challenge in Low Resource Settings: Case Report and Review of the Literature.

D-bifunctional protein deficiency (D-BPD) is a rare, autosomal recessive peroxisomal disorder that affects the breakdown of long-chain fatty acids. Patients with D-BPD typically present during the neonatal period with hypotonia, seizures, and facial dysmorphism, followed by severe developmental delay and early mortality. While some patients have survived past two years of age, the detectable enzyme activity in these rare cases was likely a contributing factor. We report a D-BPD case and comment on challenges faced in diagnosis based on a narrative literature review. An overview of Romania's first patient diagnosed with D-BPD is provided, including clinical presentation, imaging, biochemical, molecular data, and clinical course. Establishing a diagnosis can be challenging, as the clinical picture is often incomplete or similar to many other conditions. Our patient was diagnosed with type I D-BPD based on whole-exome sequencing (WES) results revealing a pathogenic frameshift variant of the HSD17B4 gene, c788del, p(Pro263GInfs*2), previously identified in another D-BPD patient. WES also identified a variant of the SUOX gene with unclear significance. We advocate for using molecular diagnosis in critically ill newborns and infants to improve care, reduce healthcare costs, and allow for familial counseling.

Bases neurobiológicas de la epilepsia neonatal y sus comorbilidades / Neurobiological basis of neonatal epilepsy and its co morbilities

Resumen La aparición de convulsiones es frecuente durante el periodo neonatal debido a las características de inma durez funcional del cerebro es este periodo. La aparición de estas convulsiones puede llevar a un diagnóstico de epilepsia neonatal, que suele estar asociado a alteracio nes estructurales del cerebro durante el neurodesarrollo. Aproximadamente el 50% de las personas con epilepsia activa padecen al menos un trastorno médico comórbi do, y esto hace que cambie la evolución de la epilepsia. La presencia de trastornos neurológicos que preceden a la aparición de la epilepsia indica que alteraciones es tructurales y/o funcionales del cerebro subyacentes pue den ser causa de la predisposición a padecer epilepsia y de los procesos comórbidos de manera independiente. En esta revisión describimos los procesos cerebrales estructurales y funcionales que subyacen a la aparición de epilepsia neonatal y sus comorbilidades.

Abstract The occurrence of seizures is frequent during the neonatal period due to the functional immaturity of the brain.The presence of these seizures may lead to a diagnosis of neonatal epilepsy, which is usually as sociated with structural alterations of the brain during neurodevelopment. Approximately 50% of people with active epilepsy have at least one comorbid medical di sorder, and the existence of a comorbid process changes the course of the epilepsy. The presence of neurologic disorders preceding the onset of epilepsy indicates that underlying neurobiological alterations may indepen dently cause the predisposition to epilepsy and comor bid processes. In this review we describe the structural and functional brain processes underlying the onset of neonatal epilepsy and its comorbidities.

Hypoxic-ischaemic encephalopathy code: A systematic review for resource-limited settings.

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia (TH), continuous electroencephalographic monitoring and magnetic resonance imaging (MRI) in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term "HIE Code", evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: (1) prevention of HIE, (2) resuscitation, (3) first 6h post birth, (4) identification and grading of encephalopathy, (5) seizure management, (6) other therapeutic interventions, (7) multiple organ dysfunction, (8) diagnostic tests and (9) family care.

Comparative Outcomes of Levetiracetam and Phenobarbital Usage in the Treatment of Neonatal Seizures: A Retrospective Analysis.

OBJECTIVES AND AIM: The primary aim of this study was to conduct a comparative analysis of the safety and efficacy of levetiracetam (LEV) and phenobarbital (PB) as first-line treatments for neonatal seizure management. This study was designed to measure and compare the incidence of adverse effects and to determine the discharge and mortality rates associated with the use of these antiseizure medications (ASMs). Through this comparison, this research sought to provide insights to optimise care for neonates experiencing seizures. MATERIALS AND METHODS: This retrospective cohort study evaluated 104 neonates treated for seizures at Zeynep Kamil Hospital from 2015 to 2020 after excluding those on non-PB/LEV antiseizure medications. Seizures were characterised using electroencephalogram (EEG) and categorised according to aetiology and frequency. Treatment efficacy was gauged by seizure cessation, as confirmed using EEG. Adverse effects and demographic data were recorded. Statistical analyses were conducted using SPSS, employing the Shapiro-Wilk, independent t-test, Mann-Whitney U test, and chi-square test, with a significance threshold of p < 0.05. RESULTS: Overall, 104 neonates treated with first-line ASM were evaluated for efficacy; PB was administered in 68.26% of the cases, while LEV was utilised in 31.74%. The total complete response rate was 40.38%, with no significant difference between the PB and LEV groups (p = 0.309). The incidence rate ratios (IRRs) demonstrated that seizure frequency profoundly influenced treatment effectiveness, with IRRs of 2.09 for rare seizures, 3.25 for frequent seizures, and 4.01 for status epilepticus, indicating a higher treatment response rate with increasing seizure frequency. For second-line treatment, among a subset of 62 patients, PB had a slight, non-significant advantage over LEV, with an odds ratio of 1.09, suggesting a marginally better response to LEV. Adverse events were significantly more frequent in the PB group, affecting 19 of 67 neonates (28.36%), compared to only 2 of 71 neonates (2.82%) in the LEV group (p < 0.001). No significant difference was observed in the discharge rates between the two groups (PB, 67.61%; LEV, 75.76%; p = 0.674). Interestingly, the mortality rate was significantly higher in the LEV group (45.45%) than that in the PB group (22.54%; p = 0.045). CONCLUSION: This study underscores LEV's superior safety profile over PB in neonatal seizure management, evidenced by a significantly lower rate of adverse events. PB seems to be more effective in the second-line treatment of neonatal seizures. Despite the lack of significant differences in the discharge rates, the higher mortality rate associated with LEV warrants further investigation. These findings advocate the cautious selection of antiepileptic drugs in neonatal care, with a preference for LEV based on its safety profile.

[Neurobiological basis of neonatal epilepsy and its comorbilities]. / Bases neurobiológicas de la epilepsia neonatal y sus comorbilidades.

The occurrence of seizures is frequent during the neonatal period due to the functional immaturity of the brain.The presence of these seizures may lead to a diagnosis of neonatal epilepsy, which is usually associated with structural alterations of the brain during neurodevelopment. Approximately 50% of people with active epilepsy have at least one comorbid medical disorder, and the existence of a comorbid process changes the course of the epilepsy. The presence of neurologic disorders preceding the onset of epilepsy indicates that underlying neurobiological alterations may independently cause the predisposition to epilepsy and comorbid processes. In this review we describe the structural and functional brain processes underlying the onset of neonatal epilepsy and its comorbidities.

La aparición de convulsiones es frecuente durante el periodo neonatal debido a las características de inmadurez funcional del cerebro es este periodo. La aparición de estas convulsiones puede llevar a un diagnóstico de epilepsia neonatal, que suele estar asociado a alteraciones estructurales del cerebro durante el neurodesarrollo. Aproximadamente el 50% de las personas con epilepsia activa padecen al menos un trastorno médico comórbido, y esto hace que cambie la evolución de la epilepsia. La presencia de trastornos neurológicos que preceden a la aparición de la epilepsia indica que alteraciones estructurales y/o funcionales del cerebro subyacentes pueden ser causa de la predisposición a padecer epilepsia y de los procesos comórbidos de manera independiente. En esta revisión describimos los procesos cerebrales estructurales y funcionales que subyacen a la aparición de epilepsia neonatal y sus comorbilidades.