Management Of Neonatal Seizures Research Articles

Neonatal Seizures.

Neonatal seizures are common among patients with acute brain injury or critical illness and can be difficult to diagnose and treat. The most common etiology of neonatal seizures is hypoxic-ischemic encephalopathy, with other common causes including ischemic stroke and intracranial hemorrhage. Neonatal clinicians can use a standardized approach to patients with suspected or confirmed neonatal seizures that entails laboratory testing, neuromonitoring, and brain imaging. The primary goals of management of neonatal seizures are to identify the underlying cause, correct it if possible, and prevent further brain injury. This article reviews recent evidence-based guidelines for the treatment of neonatal seizures and discusses the long-term outcomes of patients with neonatal seizures.

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

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. 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. 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). 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.

Neonatal Seizures in Low- and Middle-Income Countries: A Review of the Literature and Recommendations for the Management.

Neonatal seizures are a common cause of neonatal intensive care unit (NICU) admission and a significant source of morbidity and mortality worldwide. Over the recent decades, there have been significant improvements in perinatal and neonatal medicine and electroencephalograp hic monitoring that have enhanced the diagnosis and treatment of neonatal seizures in highincome countries. However, the management of neonatal seizures remains a major challenge in low- to middle-income countries, where the availabilityof resources is limited. The purpose of this article is to present a comprehensive review of the current evidence on the etiology, pathophysiology, diagnosis, and treatment of neonatal seizures and to offer practical management recommendations that could be implemented in resource-limited settings. Cite this article as: Spenard S, Ivan Salazar Cerda C, Cizmeci MN. Neonatal seizures in low and middleincome countries: Review of the literature and recommendations for the management. Turk Arch Pediatr. 2024;59(1):13-22.

Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures.

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.

Management of neonatal seizures developed after the first 24 hours of life: a clinical audit from a tertiary children&amp;rsquo;s hospital, Sri Lanka

Management of neonatal seizures developed after the first 24 hours of life: a clinical audit from a tertiary children&amp;rsquo;s hospital, Sri Lanka

Aluminum Thin Film Nanostructure Traces in Pediatric EEG Net for MRI and CT Artifact Reduction.

Magnetic resonance imaging (MRI) and continuous electroencephalogram (EEG) monitoring are essential in the clinical management of neonatal seizures. EEG electrodes, however, can significantly degrade the image quality of both MRI and CT due to substantial metallic artifacts and distortions. Thus, we developed a novel thin film trace EEG net ("NeoNet") for improved MRI and CT image quality without compromising the EEG signal quality. The aluminum thin film traces were fabricated with an ultra-high-aspect ratio (up to 17,000:1, with dimensions 30 nm × 50.8 cm × 100 µm), resulting in a low density for reducing CT artifacts and a low conductivity for reducing MRI artifacts. We also used numerical simulation to investigate the effects of EEG nets on the B1 transmit field distortion in 3 T MRI. Specifically, the simulations predicted a 65% and 138% B1 transmit field distortion higher for the commercially available copper-based EEG net ("CuNet", with and without current limiting resistors, respectively) than with NeoNet. Additionally, two board-certified neuroradiologists, blinded to the presence or absence of NeoNet, compared the image quality of MRI images obtained in an adult and two children with and without the NeoNet device and found no significant difference in the degree of artifact or image distortion. Additionally, the use of NeoNet did not cause either: (i) CT scan artifacts or (ii) impact the quality of EEG recording. Finally, MRI safety testing confirmed a maximum temperature rise associated with the NeoNet device in a child head-phantom to be 0.84 °C after 30 min of high-power scanning, which is within the acceptance criteria for the temperature for 1 h of normal operating mode scanning as per the FDA guidelines. Therefore, the proposed NeoNet device has the potential to allow for concurrent EEG acquisition and MRI or CT scanning without significant image artifacts, facilitating clinical care and EEG/fMRI pediatric research.

Evaluation of Adverse Outcome Predictors in Neonatal Seizure: A Longitudinal Study from a Tertiary Centre of Eastern India

Introduction: Neonatal seizures are common but can be manifestations of serious underlying disorders and sometimes have a grave prognosis. Predictors for adverse outcomes are important for early referral and advanced interventions. Aim: To study the incidence and factors associated with neonatal seizure and to determine the predictors of adverse outcomes. Materials and Methods: This was a longitudinal study, conducted from April 2020 to March 2021 at a Rural Medical College (Midnapore Medical College and Hospital, West Bengal) in Eastern India. All the admitted newborns (N=143) in the Special Newborn Care Unit (SNCU), who had clinically evident seizures, were included in the study. Data were collected regarding the perinatal history, gestational age, type of delivery, birth weight, APGAR score at 1 and 5 minutes, and need for resuscitation at birth. The onset of the seizure, seizure type, investigation findings, possible aetiological diagnosis, and final outcome was noted. The management of neonatal seizures was as per the institutional protocol. Babies were followed up for a minimum of 28 days or throughout their hospital stay till discharge/death. The outcome was categorised into two categories: ‘favourable’ when there was a normal neurological examination and ‘unfavourable’ when there was any neurological impairment or death. Statistical analyses were performed using the Statistical Package for Social Sciences software version 25 (SPSS Inc., Chicago, IL, USA). Risk factors were determined by analysing outcomes using simple and multivariate logistic regression analysis. The p-values less than 0.05 were considered as statistically significant. Results: A total of 143 newborns had seizures out of 3126, making the incidence of neonatal seizures 4.57%. Males outnumbered females. Total 64.33% were preterm. Five minutes APGAR score &lt;7 was noticed in 44.75%. The most common type was subtle seizure. Advanced resuscitation manoeuvre was required for 46.8% cases whereas mechanical ventilation was required in 11.88%. The most common aetiology was birth asphyxia (46.15%), and the cranial ultrasound showed Hypoxic Ishchaemic Encephalopathy (HIE) changes in 30.77% of cases. Multiple logistic regressions revealed only four factors, namely, preterm delivery (OR 5.82), need for extensive resuscitation manoeuvre (OR 6.21), presence of status epilepticus (OR 3.49) and abnormal cranial ultrasound (OR 1.02) to be the independent risk factors for unfavourable outcome. Conclusion: Clinical diagnosis of neonatal seizure could be useful in resource poor centers, where video-Electroencephalogram (EEG) is not available. Premature delivery, need for extensive resuscitation, presence of status epilepticus and abnormal cranial ultrasound were associated with poor short-term outcome.

Expert consensus on clinical management of neonatal seizures

新生儿惊厥的病死率逐渐降低，但远期不良结局的发生率仍然较高。新生儿脑电生理监测的普及显著提高了新生儿惊厥的诊断率和正确率。由于缺乏循证医学依据支持，有关惊厥诊断、严重度评估、何时启动抗惊厥药物治疗以及如何停药在现有指南中存在差异。中华医学会儿科学分会新生儿学组和中华儿科杂志编辑委员会组织新生儿科专家在复习国内外相关文献的基础上，制定了“新生儿惊厥临床管理专家共识（2022版）”，为临床上新生儿惊厥评估、监测及治疗建立相对的实践标准。.

Neonatal EEG seizure detection using a new signal structural complexity measure based on matching pursuit decomposition with nonstationary dictionary

Background and objectiveIn newborns, it is often difficult to accurately differentiate between seizure and non-seizure based solely on clinical manifestations. This highlights the importance of electroencephalogram (EEG) in the recognition and management of neonatal seizures. This paper proposes an effective algorithm for the detection of neonatal seizure using multichannel EEG. MethodsNeonatal EEG changes morphology as it alternates between seizure and non-seizure states. A new signal complexity measure based on matching pursuit (MP) decomposition is proposed and used to detect transitions between these two states. The new measure, referred to as weighted structural complexity (WSC), was used for the detection of seizures in 30 newborn EEG records. Multiple IIR filters and an MP-based filter were designed and used to remove artifacts from the EEG data. Geometrical correlation between the EEG data channels was applied to reduce the number of false detections caused by remnant artifacts. The seizure detector's performance was assessed using several epoch-based (e.g., accuracy) and event-based (GDR = good detection rate and FD/h = false detections per hour) metrics. ResultsCompared to the neurologist marking, the proposed detector was able to detect EEG seizures with 94% accuracy, 90.9% GDR, and 0.14 FD/h (95% CI: [0.06, 0.34]). ConclusionsThe high performance of the MP-based detector may have significant implications for the accurate diagnosis of neonatal seizures and the appropriate use of anticonvulsants and ongoing clinical assessment and care of the newborn.

Continuous EEG monitoring still recommended for neonatal seizure management: commentary on NEST trial.

Continuous EEG monitoring still recommended for neonatal seizure management: commentary on NEST trial.

Efficacy and Utilization Patterns of Anti-Epileptic Drugs in the Management of Neonatal Seizures: A Comparative Exploration.

Management of neonatal seizures with available limited guidelines across different gestation can cause long-term neurological and cognitive impairment. To compare utilization and observe the efficacy of anti-epileptic drugs in the treatment of neonatal seizures. The association of hypoxic-ischemic encephalopathy with NS and the etiology of HIE were also determined. A retrospective cohort study was conducted at a tertiary care hospital for a period of one year. It was approved by IEC prior to initiation. Neonates admitted for seizure management and perinatal asphyxia with hypoxic-ischemic encephalopathy were included in the study. Both term and preterm 267 neonates from January 2014 to July 2018 were retrospectively analyzed. The drugs with the fastest seizure resolution, least recurrence, and readmission rates were considered efficient. Phenobarbitone, levetiracetam, and phenytoin were compared as they were commonly prescribed. Inpatient medical records and hospital databases served as sources of information. Phenobarbitone was commonly utilized, followed by phenytoin and levetiracetam. The commonly prescribed combination was phenobarbitone (first-line agent) and phenytoin (second-line agent). Phenobarbitone immediately resolved seizures (97, 75.1%) and had the least cases of seizure recurrences (53, 41.1%) and readmissions (20, 15.5%), making it most efficient. The best second-line agent was phenytoin, with the least seizure recurrence (4, 8.51%), least readmissions (7, 14.8%), and fastest resolution (25, 53.1%). Levetiracetam was an efficient third-line agent. Hypoxic-ischemic encephalopathy was the most observed cause of neonatal seizures. Phenobarbitone was observed as the most utilized and efficient anti-epileptic drug, followed by phenytoin and levetiracetam. Owing to limitations in this study, there is an alarming need for standardized clinical trials to establish thorough guidelines.

Current and Future Uses of Continuous EEG in the NICU.

Continuous EEG (cEEG) is a fundamental neurodiagnostic tool in the care of critically ill neonates and is increasingly recommended. cEEG enhances prognostication via assessment of the background brain activity, plays a role in predicting which neonates are at risk for seizures when combined with clinical factors, and allows for accurate diagnosis and management of neonatal seizures. Continuous EEG is the gold standard method for diagnosis of neonatal seizures and should be used for detection of seizures in high-risk clinical conditions, differential diagnosis of paroxysmal events, and assessment of response to treatment. High costs associated with cEEG are a limiting factor in its widespread implementation. Centralized remote cEEG interpretation, automated seizure detection, and pre-natal EEG are potential future applications of this neurodiagnostic tool.

Treatment of Neonatal Seizures: Comparison of Treatment Pathways From 11 Neonatal Intensive Care Units

ObjectiveSeizures are a common neonatal neurologic emergency. Many centers have developed pathways to optimize management. We evaluated neonatal seizure management pathways at level IV neonatal intensive care units (NICUs) in the United States to highlight areas of consensus and describe aspects of variability. MethodsWe conducted a descriptive analysis of 11 neonatal seizure management pathways from level IV NICUs that specialize in neonatal neurocritical care including guidelines for electroencephalography (EEG) monitoring, antiseizure medication (ASM) choice, timing, and dose. ResultsStudy center NICUs had a median of 70 beds (interquartile range: 52-96). All sites had 24/7 conventional EEG initiation, monitoring, and review capability. Management pathways uniformly included prompt EEG confirmation of seizures. Most pathways included a provision for intravenous benzodiazepine administration if either EEG or loading of ASM was delayed. Phenobarbital 20 mg/kg IV was the first-line ASM in all pathways. Pathways included either fosphenytoin or levetiracetam as the second-line ASM with variable dosing. Third-line ASMs were most commonly fosphenytoin or levetiracetam, with alternatives including topiramate or lacosamide. All pathways provided escalation to continuous midazolam infusion with variable dosing for seizures refractory to initial medication trials. Three pathways also included lidocaine infusion. Nine pathways discussed ASM discontinuation after resolution of acute symptomatic seizures with variable timing. ConclusionsDespite a paucity of data from controlled trials regarding optimal neonatal seizure management, there are areas of broad agreement among institutional pathways. Areas of substantial heterogeneity that require further research include optimal second-line ASM, dosage, and timing of ASM discontinuation.

Neonatal Seizure Management: Is the Timing of Treatment Critical?

ObjectiveTo assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden and describe overall seizure management in a large neonatal cohort.Study designNewborns (36-44 weeks of gestation) requiring electroencephalographic (EEG) monitoring recruited to 2 multicenter European studies were included. Infants who received antiseizure medication exclusively after electrographic seizure onset were grouped based on the time to treatment of the first seizure: antiseizure medication within 1 hour, between 1 and 2 hours, and after 2 hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures, and antiseizure medication dose over the first 24 hours after seizure onset.ResultsOut of 472 newborns recruited, 154 (32.6%) had confirmed electrographic seizures. Sixty-nine infants received antiseizure medication exclusively after the onset of electrographic seizure, including 21 infants within 1 hour of seizure onset, 15 between 1 and 2 hours after seizure onset, and 33 at >2 hours after seizure onset. Significantly lower seizure burden and fewer seizures were noted in the infants treated with antiseizure medication within 1 hour of seizure onset (P = .029 and .035, respectively). Overall, 258 of 472 infants (54.7%) received antiseizure medication during the study period, of whom 40 without electrographic seizures received treatment exclusively during EEG monitoring and 11 with electrographic seizures received no treatment.ConclusionsTreatment of neonatal seizures may be time-critical, but more research is needed to confirm this. Improvements in neonatal seizure diagnosis and treatment are also needed.

Clinical and biochemical profile of neonatal seizures admitted in neonatal intensive care unit of a tertiary care hospital

Background: Several factors contribute to seizures among neonates. To avoid complications from under recognition of clinical seizures and the adverse effects of medications administered, the diagnosis and management of neonatal seizures necessitate an interprofessional approach. Present study was done to study the clinical and biochemical profile of neonates with seizures admitted to a tertiary care hospital, Chennai.Methods: A cross sectional study was conducted where all the neonates from birth to 28 days of life who got admitted in the neonatal intensive care unit (NICU) of a tertiary care hospital-Shri Sathya Sai medical college and research institute were included in the study. Baseline characteristics of all the babies were noted on the prescribed proforma. Thorough physical examination was done and seizures were diagnosed by clinical observation. Clinical details of each seizure episode were recorded like age at onset of seizures, duration of seizure, number and type of seizure.Results: In the present study, 50 neonates satisfying the inclusion and exclusion criteria were included in the study. The main mode of delivery was normal vaginal delivery (50%) followed by LSCS (40%) and assisted delivery (10%). 54% were male and 46% were female and majority of babies were delivered at term i.e., 72% and 28% were pre term babies. The mean day of onset of seizures in the present study was 3.18±2.09. Based on day of onset of seizures, with in 24 hrs (28%), 24 hrs to 72 hrs (46%), 4th day to 1 week (22%), more than 1 week (4%). Based on type of seizure 64% had subtle type, 26% had tonic type and 10% had clonic type of seizures. In this study, 24% had hypoglycemia, and 10 (20%) had hypocalcemia, 14% in the present study had hyponatremia, and 2 (4%) had hypomagnesemia, 2 (4%) had hypernatremia, 6% had combination of hypocalcemia and hypoglycemia.Conclusions: Hypocalcemia, hypoglycemia, hyponatremia were the common biochemical abnormalities observed in our study. Subtle seizures were the common type of seizures observed among both pre term and term infants.

The Pharmacokinetics of Crushed Levetiracetam Tablets Administered to Neonates.

Intravenous phenobarbital remains the first-line therapy in the management of neonatal seizures. Shortages of intravenous phenobarbital in South Africa necessitated the addition of oral levetiracetam as part of management of neonatal seizures. We evaluated the pharmacokinetics of crushed immediate-release levetiracetam tablets administered to neonates to terminate seizures. A prospective, observational study of neonates admitted with seizures to Tygerberg Hospital. Participants received crushed levetiracetam (diluted in saline) given orally or via naso-/orogastric tube. At steady-state, pharmacokinetic sampling was performed at pre-dose, 1.5, 2.5 and 4 h post-dose. Maximum concentration (Cmax), time to Cmax (Tmax), trough concentrations (Ctrough) and area under the concentration-time curve (AUC0-12) were calculated using non-compartmental analysis. Seizure termination and safety profiles were documented. Nineteen participants were grouped into three dosing ranges: (i) 5-15 mg/kg/12-hourly, (ii) 15-25 mg/kg/12-hourly and (iii) 25-35 mg/kg/12-hourly. Range 1 demonstrated AUC0-12 167.0 ± 45.6 h*μg/mL, Cmax 19.19 ± 4.12 μg/mL and Ctrough 9.99 ± 3.86 µg/mL. Range 2, AUC0-12 316.5 ± 108.4 h*μg/mL, Cmax 35.12 ± 10.54 µg/mL and Ctrough 19.25 ± 8.48 µg/mL. Range 3, AUC0-12 290.9 (range 176.14-405.59) h*μg/mL, Cmax 36.11 (range 27.58-44.64) µg/mL and Ctrough 13.03 (2.98-23.07) µg/mL. Seizures terminated in 17/19 (90%) neonates by day 3 and 19/19 (100%) by day 4 post-levetiracetam initiation. Crushed levetiracetam has comparable pharmacokinetics to historical data. No pharmacokinetic differences were observed between oral vs. naso-/orogastric administration. Crushed levetiracetam tablets can be considered for neonates in low-resource settings where intravenous and syrup access is limited. Intravenous preparations of antiepileptic medications are used in the management of neonatal seizures. Various established standard of care intravenous antiepileptic medicines are unavailable nationally and internationally due to reasons outside our control. This stock shortage included intravenous phenobarbitone which is the first-line treatment for paediatric seizures. Due to phenobarbital shortage, levetiracetam has been identified by the neonatologists at Tygerberg Hospital, Cape Town, South Africa, as a suitable treatment option due to its efficacy and safety profile. However, intravenous levetiracetam and oral syrup is not registered in South Africa. Levetiracetam tablets are being crushed, dissolved and administered to neonates. There are no data available on the absorption of crushed levetiracetam tablets administered to neonates via a nasogastric tube. This study characterized the pharmacokinetic profile of crushed levetiracetam administered to neonates. We selected neonates receiving levetiracetam from the neonatal wards at Tygerberg hospital and drew blood to analyse the levetiracetam concentrations at 4 different time points. We found that the overall exposure of crushed levetiracetam tablets were comparable to the exposures achieved in historical data of the unaltered formulations. We concluded that crushed levetiracetam tablets can be considered for neonates in low resource settings where intravenous and syrup access is limited.

Recent Advances in the Diagnosis and Treatment of Neonatal Seizures.

Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroencephalogram (EEG) is the gold standard for monitoring neonatal seizures, amplitude-integrated EEGs have gained significant popularity in resource-limited settings. There is tremendous progress in the automated seizure detection algorithm, including the availability of a fully convolutional neural network using artificial machine learning (deep learning). There is a substantial need for ongoing research and clinical trials to understand optimal medication selection (first line, second line, and third line) for neonatal seizures, treatment duration of antiepileptic drugs after cessation of seizures, and strategies to improve neuromorbidities such as cerebral palsy, epilepsy, and developmental impairments. Although in recent times, levetiracetam use has been significantly increased for neonatal seizures, a multicenter, randomized, blinded, controlled phase IIb trial confirmed the superiority of phenobarbital over levetiracetam in the acute suppression of neonatal seizures. While there is no single best choice available for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.

Efficacy of Levetiracetam in neonatal seizures: a systematic review

Background Neonatal seizures represent the most frequent presenting sign of any neurological abnormality secondary to various etiologies in the neonatal period. Phenobarbitone (PB) has been used as first-line anti-epileptic drug in the treatment of seizures but concerns have been raised regarding its neuro-apoptotic effects over the developing brain. Levetiracetam (LEV) is a newer anti-epileptic drug with neuroprotective property and has been used in adults and pediatric patient but its use in neonates have very limited experience. Recently many neonatal studies have sought the role of LEV in the management of neonatal seizures. Aims and objective To evaluate the efficacy of Levetiracetam in the management of neonatal seizures. Search methods The literature search was done for this systematic review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), and other various electronic databases including PubMed and various sites for ongoing trials and abstracts of conferences. Results Two eligible studies were analyzed that fulfilled the inclusion criteria of the systematic review. Fifteen studies were excluded due to the non-fulfillment of inclusion criteria. The primary outcome of both studies was to see the efficiency of LEV in controlling neonatal seizures when compared to PB. Better seizure control after a single loading dose of LEV was seen. Rates of seizure cessation at 24 h was also better in the LEV arm. Neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE) and receiving therapeutic hypothermia were better controlled with LEV. The side effect of LEV was significantly less when compared to PB. Conclusion Levetiracetam has shown to have promising anti-epileptic properties for the management of neonatal seizure with better efficacy and less or no side effects. There is a need to conduct more randomized controlled trials seeking the role of LEV in the acute management of neonatal seizures and also for assessing its neuroprotective role and neurodevelopmental outcome in these neonates.

Investigating and managing neonatal seizures in the UK: an explanatory sequential mixed methods approach

BackgroundNeonatal seizures are difficult to diagnose and, when they are, tradition dictates first line treatment is phenobarbital. There is little data on how consultants diagnose neonatal seizures, choose when to treat or how they choose aetiological investigations or drug treatments. The purpose of this study was to assess the variation across the UK in the management of neonatal seizures and explore paediatricians’ views on their diagnosis and treatment.MethodsAn explanatory sequential mixed methods approach was used (QUAN→QUAL) with equal waiting between stages. We collected quantitative data from neonatology staff and paediatric neurologists using a questionnaire sent to neonatal units and via emails from the British Paediatric Neurology Association. We asked for copies of neonatal unit guidelines on the management of seizures. The data from questionnaires was used to identify16 consultants using semi-structured interviews. Thematic analysis was used to interpret qualitative data, which was triangulated with quantitative questionnaire data.ResultsOne hundred questionnaires were returned: 47.7% thought levetiracetam was as, or equally, effective as phenobarbital; 9.2% thought it was less effective. 79.6% of clinicians had seen no side effects in neonates with levetiracetam. 97.8% of unit guidelines recommended phenobarbital first line, with wide variation in subsequent drug choice, aetiological investigations, and advice on when to start treatment. Thematic analysis revealed three themes: ‘Managing uncertainty with neonatal seizures’, ‘Moving practice forward’ and ‘Multidisciplinary team working’. Consultants noted collecting evidence on anti-convulsant drugs in neonates is problematic, and recommended a number of solutions, including collaboration to reach consensus guidelines, to reduce diagnostic and management uncertainty.ConclusionsThere is wide variation in the management of neonatal seizures and clinicians face many uncertainties. Our data has helped reveal some of the reasons for current practice and decision making. Suggestions to improve certainty include: educational initiatives to improve the ability of neonatal staff to describe suspicious events, greater use of video, closer working between neonatologists and neurologists, further research, and a national discussion to reach a consensus on a standardised approach to managing neonatal epileptic seizures.

A Comparison Of Conventional Electroencephalography With Amplitude-Integrated EEG In Detection Of Neonatal Seizures.

IntroductionAmplitude-integrated electroencephalogram (aEEG) is widely used in Neonatal Intensive Care Units (NICUs) to monitor neonatal seizures. This method is still not well established compared to conventional electroencephalogram (cEEG), the diagnostic gold standard. However, aEEG can be a good screening tool for the diagnosis of seizures in infants. Our aim in this review study is to evaluate aEEG diagnostic accuracy in comparison with cEEG, for detection of neonatal seizures.MethodsIn this work, we studied the published articles which used EEG and aEEG in the evaluation process of seizures in neonates and compared these techniques to obtain an approach for the detection of neonatal seizures.ResultsSeventeen articles were included. Using aEEG with raw trace to detect individual seizures showed median sensitivity of 78% (range: 68–85) and median specificity of 78% (range: 71–84). The median sensitivity and specificity were 54% (range: 25–95) and 81% (range: 50–100), respectively, in case of using aEEG without raw traces. Brief duration seizures and those occurring away from aEEG leads were less detected.ConclusionStudies showed that aEEG has variable sensitivity and specificity. Based on the evidences, aEEG cannot be recommended as the only way for diagnosis and management of seizures in neonates; however, it could complete the diagnosis of seizures in the infant and could be a very good tool for screening seizures.