Seizures In Newborns Research Articles

The temporal characteristics of seizures in neonatal hypoxic ischemic encephalopathy treated with hypothermia

PurposeThe characteristics of electrographic seizures in newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) are poorly described. This retrospective, observational study provides reference data on the characteristics of seizures and their evolution over time in newborns with HIE receiving whole-body TH. MethodThe cohort under analysis included 23 infants with HIE and seizures defined by multi-channel EEG recordings. Clinical presentation, details of TH and antiepileptic drugs used were recorded. Time from first to last-recorded electrographic seizure (seizure period) was calculated. Temporal characteristics of seizures – total burden, duration, number, burden in minutes per hour, distribution of burden over time (temporal evolution), time from seizure onset to maximum seizure burden (Tmsb), T1, and time from Tmsb to seizure offset, T2 – were analysed. ResultsThe median age at electrographic seizure onset was 13.1h (IQR: 11.4 to 22.0). Tmsb was reached at a median age of 19.4hours (IQR: 12.2 to 29.7). Median seizure period was 16.5h (IQR: 7.0 to 49.7), median number of seizures per hour was 1.9 (IQR: 1.0 to 3.3). The seizure burden was 4.0min/h (IQR: 2.0 to 7.0). There was no consistent pattern in the temporal evolution of seizures in neonates treated with TH. The skewness was neither positive nor negative (p-value=0.15), there was no difference between the duration of T1 and T2 (p-value=0.09) and no difference in the seizure burden between T1 and T2 (p=0.09).There was an association between Tmsb and Phenobarbital (PB) administration (r=0.76, p-value<0.001). ConclusionThere is no consistent temporal evolution of seizure burden in neonates treated with TH. Seizures are diffuse, and their characteristics are variable.

Neonatal seizures in the 21st century

The diagnosis and management of neonatal seizures remains as troublesome today as it was in the 20th century. The epidemiology of neonatal seizures has been studied more recently with gains in information regarding risk factors in the mother, infant and puerperium. Today, hypoxic ischemic encephalopathy still remains the most important risk factor for seizures, even in developing countries where infections are very prominent causes of early onset neonatal seizures [1,2]. Recent guidelines from the Global Campaign against Epilepsy sponsored by the International League Against Epilepsy and the World Health Organization have been published for care of newborns with seizures that could be applicable throughout the world, regardless of medical resources [3]. The algorithm takes into account the most common causes of newborn seizures as stated above but also includes treatable metabolic causes like hypoglycemia, hypocalcemia and disturbances of sodium and magnesium levels. It is clear that interventions that target hypoxic ischemic encephalopathy will lead to lower rates of seizures in the newborn period. Since preterm infants have a higher risk of seizure than term born, prevention of preterm birth would certainly achieve this goal. Puerperial events like prolonged labor and post-dates delivery are modifiable risk factors. When performing

To study the incidence, etiology and EEG profile of neonatal seizures: a prospective observational study from India

Aim: To study the incidence, etiology and electroencephalography (EEG) profile of neonatal seizures and also to study the correlation between clinical picture and EEG appearance. Type of study: Prospective observational cohort study. Study duration: September 2011 to April 2013. Inclusion and exclusion: Seizures within first 28 d of life and seizures documented by doctors. Population: Neonates admitted in intensive care unit: intramural (4412) and extramural (1900) admissions (all together 6312). Materials and methods: One hundred and seventy-two neonates with seizures were enrolled. All the neonates were evaluated with necessary investigation, ultrasound head and CT scan. All the neonates underwent EEG as early as possible with neonatal stabilization. The etiology of neonatal seizures, CT scan and ultrasound head, characteristic of the EEG and neonatal mortality were noted. Results: The incidence of neonatal seizure was 0.77% in the intramural and 7.3% among the extramural neonates. The incidence of seizures in term newborn was 0.7% and in preterm was 1.1%. The most common cause of neonatal seizure was hypoxic ischemic encephalopathy (HIE) followed by hypocalcemia. The predominant seizure type was multifocal (51%) followed by subtle seizure (43%). There was an EEG abnormality in 72% of the total EEG with varied patterns. The mortality rate in the cohort was 15% with HIE being the most common cause. Conclusion: Most common cases of neonatal seizure were HIE and with the most common type being multifocal. EEG was abnormal in the majority of the neonates with various pattern of abnormality.

Stereological investigation in the effects of curcumin on the phenobarbital caused hippocampal damage during development

* Correspondence to: Burcu Demirel Department of Forestry, Akkus Vocational High School, Ordu University, Ordu, Turkey e-mail: bioburcudemirel@gmail.com Phenobarbital is an antiepileptic drug used for the treatment of seizures in newborns, children and adults. Despite having positive effect in the treatment of epilepsy, phenobarbital may adversely affect brain function and brain development. Antioxidant and neuroprotective properties of curcumin are well-known. Curcumin has a significant effect in the treatment of various diseases caused by oxidative stress. In the light of this information, the study aimed to determine the adverse effects of phenobarbital in the number of pyramidal cells in the hippocampus of the developing rat brain and whether curcumin has protective effects against these adverse effects. A total of 50 Wistar male rats were divided into two groups as 7 and 14-day old. Each group was subdivided into five groups as control, curcumin, dimethyl sulfoxide, phenobarbital, phenobarbital+curcumin. After dissolving in 10% dimethylsulfoxide, the rats in each group received intraperitoneal injection of phenobarbital (75 mg/kg) and curcumin (200 mg/kg). Rats were sacrificed 24 hours after the last injection. After histological processes, stereological analysis was performed using optical fractionation technique. Overall number of neurons in the left hippocampus of the 7 and 14-day old rats (CA1, CA2, CA3 and CA4) was estimated and average numerical values were determined. The mean total neuron numbers and standard deviations for 7-day old rats were 727224±4531.7 in control group; 416111.5±29413.9 in phenobarbital group and 587136.5±36337.9 in phenobarbital+curcumin group. These numerical values were 508160.6±21985.2; 353817.6±24101.78 and 492470.9±36225 for 14-day old rats respectively. Results showed that cellular damage in the hippocampus of developing rat brain (7-day and 14-day) caused by phenobarbital, also used in childhood epilepsy, can be prevented by curcumin, a powerful antioxidant. In the opinion, the results of this study will shed light on clinical studies and form a basis to antioxidant studies involving the use of phenobarbital.

Stereological investigation of the effects of curcumin on the damage in the hippocampus of developing rat brain caused by valproic acid

Valproic acid is an antiepileptic drug used for the treatment of seizures in newborns, children and adults. Despite having positive effect in the treatment of epilepsy, valproic acid may adversely affect brain function and brain development. Antioxidant and neuroprotective properties of curcumin are well-known. Curcumin has a significant effect in the treatment of various diseases caused by oxidative stress. In the light of this information, the study aimed to determine the adverse effects of valproic acid in the number of pyramidal cells in the hippocampus of the developing rat brain and whether curcumin has protective effects against these adverse effects. A total of 50 Wistar male rats were divided into two groups as 7 and 14 day old. Each group was subdivided into five groups as control, curcumin, dimethyl sulfoxide, valproic acid, valproic acid+curcumin. After dissolving in 10% dimethylsulfoxide, the rats in each group received intraperitoneal injection of valproic acid (400 mg/kg) and curcumin (200 mg/kg). Rats were sacrificed 24 hours after the last injection. After histological processes, stereological analysis was performed using optical fractionation technique. Overall number of neurons in the left hippocampus (CA1, CA2, CA3 and CA4) of the 7 and 14 day old rats was estimated and average numerical values were determined. The mean total neuron numbers and standard deviations for 7 day old rats were 727224±4531.7 in control group; 312232.8±15853.3 in valproic acid group and 431665.4±28464.5 in valproic acid+curcumin group. These numerical values were 508160.6±21985.2; 313958.9±18199.66 and 456028.8±24942.9 for 14 day old rats respectively. The results support the idea that curcumin can be a potential protective and effective agent in the prevention of histological neuronal damage that may occur in the developing rat brain due to valproic acid treatment. We are in the opinion that the results of this study will shed light on clinical studies and form a basis to antioxidant studies involving the use of valproric acid.

043 — (MAR0038) The influence of neonatal seizures on epileptogenesis

Rationale: Seizures in newborns (NBs) remain the most frequent neurological problem in the nursery. Although seizures per se do not cause irreversible damage in the immature (developing) brain, NB seizures may immediately alter some electrical parameters and behavioral patterns. However, it remains unclear whether or not NBs who had seizures will be more prone to develop epilepsy later in life. The effects caused by seizures in this population can be either transient or persistent, and the long-term effects may occur even with no histological evidence of neuronal injury.

Neonatal seizures and therapeutic hypothermia for hypoxic-ischemic encephalopathy.

Neonatal seizures are associated with morbidity and mortality. Hypoxic-ischemic encephalopathy (HIE) is the most common cause of seizures in newborns. Neonatal animal models suggest that therapeutic hypothermia can reduce seizures and epileptiform activity in the setting of hypoxia-ischemia, however data from human studies have conflicting results. In this research highlight, we will discuss the findings of our recent study that demonstrated a decreased seizure burden in term newborns with moderate HIE treated with hypothermia.

A review of time–frequency matched filter design with application to seizure detection in multichannel newborn EEG

This paper presents a novel design of a time–frequency (t–f) matched filter as a solution to the problem of detecting a non-stationary signal in the presence of additive noise, for application to the detection of newborn seizure using multichannel EEG signals. The solution reduces to two possible t–f approaches that use a general formulation of t–f matched filters (TFMFs) based on the Wigner–Ville and cross Wigner–Ville distributions, and a third new approach based on the signal ambiguity domain representation; referred to as Radon-ambiguity detector. This contribution defines a general design formulation and then implements it for newborn seizure detection using multichannel EEG signals. Finally, the performance of different TFMFs is evaluated for different t–f kernels in terms of classification accuracy using real newborn EEG signals.Experimental results show that the detection method which uses TFMFs based on the cross Wigner–Ville distribution outperforms other approaches including the existing TFMF-based ones. The results also show that TFMFs which use high-resolution kernels such as the modified B-distribution, achieve higher detection accuracies compared to the ones which use other reduced-interference t–f kernels.

Real-time automated detection of clonic seizures in newborns

ObjectiveThe aim of this study is to apply a real-time algorithm for clonic neonatal seizures detection, based on a low complexity image processing approach extracting the differential average luminance from videotaped body movements. Methods23 video-EEGs from 12 patients containing 78 electrographically confirmed neonatal seizures of clonic type were reviewed and all movements were divided into noise, random movements, clonic seizures or other seizure types. Six video-EEGs from 5 newborns without seizures were also reviewed. Videos were then separately analyzed using either single, double or triple windows (these latter with 50% overlap) each of a 10s duration. ResultsWith a decision threshold set at 0.5, we obtained a sensitivity of 71% (corresponding specificity: 69%) with double-window processing for clonic seizures diagnosis. The discriminatory power, indicated by the Area Under the Curve (AUC), is higher with two interlaced windows (AUC=0.796) than with single (AUC=0.788) or triple-window (AUC=0.728). Among subjects without neonatal seizures, our algorithm showed a specificity of 91% with double-window processing. ConclusionsOur algorithm reliably detects neonatal clonic seizures and differentiates them from either noise, random movements and other seizure types. SignificanceIt could represent a low-cost, low complexity, real-time automated screening tool for clonic neonatal seizures.

A Multi-Channel Fusion Based Newborn Seizure Detection

We propose and compare two multi-channel fusion schemes to utilize the information extracted from simultaneously recorded multiple newborn electroencephalogram (EEG) channels for seizure detection. The first approach is known as the multi-channel feature fusion. It involves concatenating EEG feature vectors independently obtained from the different EEG channels to form a single feature vector. The second approach, called the multi-channel decision/classifier fusion, is achieved by combining the independent decisions of the different EEG channels to form an overall decision as to the existence of a newborn EEG seizure. The first approach suffers from the large dimensionality problem. In order to overcome this problem, three different dimensionality reduction techniques based on the sum, Fisher’s linear discriminant and symmetrical uncertainty (SU) were considered. It was found that feature fusion based on SU technique outperformed the other two techniques. It was also shown that feature fusion, which was developed on the basis that there was inter-dependence between recorded EEG channels, was superior to the independent decision fusion.

Comment on: “Clinical Management of Seizures in Newborns: Diagnosis and Treatment”

Comment on: “Clinical Management of Seizures in Newborns: Diagnosis and Treatment”

Authors’ Reply to Eugenio Grillo: Clinical Management of Seizures in Newborns: Diagnosis and Management

Authors’ Reply to Eugenio Grillo: Clinical Management of Seizures in Newborns: Diagnosis and Management

Detection of artifacts from high energy bursts in neonatal EEG

Detection of non-cerebral activities or artifacts, intermixed within the background EEG, is essential to discard them from subsequent pattern analysis. The problem is much harder in neonatal EEG, where the background EEG contains spikes, waves, and rapid fluctuations in amplitude and frequency. Existing artifact detection methods are mostly limited to detect only a subset of artifacts such as ocular, muscle or power line artifacts. Few methods integrate different modules, each for detection of one specific category of artifact. Furthermore, most of the reference approaches are implemented and tested on adult EEG recordings. Direct application of those methods on neonatal EEG causes performance deterioration, due to greater pattern variation and inherent complexity. A method for detection of a wide range of artifact categories in neonatal EEG is thus required. At the same time, the method should be specific enough to preserve the background EEG information. The current study describes a feature based classification approach to detect both repetitive (generated from ECG, EMG, pulse, respiration, etc.) and transient (generated from eye blinking, eye movement, patient movement, etc.) artifacts. It focuses on artifact detection within high energy burst patterns, instead of detecting artifacts within the complete background EEG with wide pattern variation. The objective is to find true burst patterns, which can later be used to identify the Burst-Suppression (BS) pattern, which is commonly observed during newborn seizure. Such selective artifact detection is proven to be more sensitive to artifacts and specific to bursts, compared to the existing artifact detection approaches applied on the complete background EEG. Several time domain, frequency domain, statistical features, and features generated by wavelet decomposition are analyzed to model the proposed bi-classification between burst and artifact segments. A feature selection method is also applied to select the feature subset producing highest classification accuracy. The suggested feature based classification method is executed using our recorded neonatal EEG dataset, consisting of burst and artifact segments. We obtain 78% sensitivity and 72% specificity as the accuracy measures. The accuracy obtained using the proposed method is found to be about 20% higher than that of the reference approaches. Joint use of the proposed method with our previous work on burst detection outperforms reference methods on simultaneous burst and artifact detection. As the proposed method supports detection of a wide range of artifact patterns, it can be improved to incorporate the detection of artifacts within other seizure patterns and background EEG information as well.

Effective implementation of time–frequency matched filter with adapted pre and postprocessing for data-dependent detection of newborn seizures

Neonatal EEG seizures often manifest as nonstationary and multicomponent signals, necessitating analysis in the time–frequency (TF) domain. This paper presents a novel neonatal seizure detector based on effective implementation of the TF matched filter. In the detection process, the TF signatures of EEG seizure are extracted to construct the TF templates used by the matched filter. Matching pursuit (MP) decomposition and narrowband filtering are proposed for the reduction of artifacts prior to seizure detection. Geometrical correlation is used to consolidate the multichannel detections and to reduce the number of false detections due to remnant artifacts. A data-dependent threshold is defined for the classification of EEG. Using 30 newborn EEG records with seizures, the classification process yielded an overall detection accuracy of 92.4% with good detection rate (GDR) of 84.8% and false detection rate of 0.36FD/h. Better detection performance (accuracy >95%) was recorded for relatively long EEG records with short seizure events.

Alteration of synaptic plasticity by neonatal seizures in rat somatosensory cortex

Seizures in newborns are associated with a high risk for subsequent epilepsy and adverse neurodevelopmental consequences. Understanding the mechanisms by which neonatal seizures adversely disturb the immature brain is important in developing therapeutic strategies. Using the convulsant agent flurothyl to mimic repetitive neonatal seizures we show that early-life seizures result in long-term alteration in the maintenance phase of long-term potentiation (LTP) in layer IV to layer II/III synapses of the somatosensory cortex without alteration of basal synaptic transmission, the induction phase of LTP and short-term depression. Such alterations may have a role in functional deficits seen following neonatal seizures.

An update on serine deficiency disorders

Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, the defect affecting the first step in the pathway, has been reported most frequently. The other two disorders in L-serine biosynthesis phosphoserine aminotransferase (PSAT) deficiency and phosphoserine phosphatase (PSP) deficiency have been reported only in a limited number of patients. The biochemical hallmarks of all three disorders are low concentrations of serine in cerebrospinal fluid and plasma. Prompt recognition of affected patients is important, since serine deficiency disorders are treatable causes of neurometabolic disorders. The use of age-related reference values for serine in CSF and plasma can be of great help in establishing a correct diagnosis of serine deficiency, in particular in newborns and young children.

Clinical Management of Seizures in Newborns

Neonatal seizures can be classified as tonic, clonic, myoclonic, and subtle. A clinical diagnosis is not easy as seizures are usually subtle in neonates. In the majority of newborn infants seizures are subclinical. On the other hand, not all abnormal movements identified by clinicians as clinical seizures are accompanied by electroencephalographic seizure discharges in the EEG. Precise incidence is difficult to delineate and depends on study population and criteria used for diagnosis of seizures. Controversy exists as to whether neonatal seizures themselves cause damage to the developing brain, or if the damage is primarily due to the underlying cause of the seizures. As a result of this controversy there is ongoing discussion whether all seizures (both clinical and subclinical) should be treated. In addition, when (sub)clinical seizures are treated, there is no consensus about the most appropriate treatment for neonatal seizures and how to assess the efficacy of treatment. Current therapeutic options to treat neonatal seizures (i.e. primarily first-generation antiepileptic drugs [AEDs]) are relatively ineffective. In practice, phenobarbital still remains the drug of first choice for EEG confirmed or suspected seizures. Benzodiazepines are also used in (phenobarbital) refractory cases. Several (small) studies indicate that lidocaine is an effective drug for refractory seizures as second- or third-line treatment. Although data are scarce, some AEDs with a wide acceptance in adult and pediatric neurology practice are being used to treat neonatal seizures (i.e. second-generation AEDs). These drugs are chemically different from all first-generation AEDs and they have an effect on other pathways so they provide new pharmacological targets for controlling seizures in newborns. Levetiracetam, topiramate, felbamate, bumetanide, lamotrigine and vigabatrin are examples of these second-generation AEDs. There is an urgent need for prospective, randomized, controlled trials to assess the efficacy and safety of these second-generation AEDs in neonates. The aim of this review is to provide an overview of the current knowledge of diagnosis, the effect on brain injury, and the treatment of neonatal seizures.

Automatic seizure detection based on the combination of newborn multi-channel EEG and HRV information

This article proposes a new method for newborn seizure detection that uses information extracted from both multi-channel electroencephalogram (EEG) and a single channel electrocardiogram (ECG). The aim of the study is to assess whether additional information extracted from ECG can improve the performance of seizure detectors based solely on EEG. Two different approaches were used to combine this extracted information. The first approach, known as feature fusion, involves combining features extracted from EEG and heart rate variability (HRV) into a single feature vector prior to feeding it to a classifier. The second approach, called classifier or decision fusion, is achieved by combining the independent decisions of the EEG and the HRV-based classifiers. Tested on recordings obtained from eight newborns with identified EEG seizures, the proposed neonatal seizure detection algorithms achieved 95.20% sensitivity and 88.60% specificity for the feature fusion case and 95.20% sensitivity and 94.30% specificity for the classifier fusion case. These results are considerably better than those involving classifiers using EEG only (80.90%, 86.50%) or HRV only (85.70%, 84.60%).

Therapeutic hypothermia in the prevention of hypoxic-ischaemic encephalopathy: new categories to be enrolled

Therapeutic hypothermia is now the standard of care for brain injury control in term infants with perinatal hypoxic ischemic encephalopathy (HIE). Accumulated evidence shows a reduction in mortality and long-term neurodevelopmental disability at 12–24 months of age, with more favourable effects in the less severe forms of HIE. Only few trials recruited newborns <36 weeks gestational age, or mild-to-moderate encephalopathy with base deficit (BD) <16. The new categories of patients to be enrolled should include (late) preterm infants, neonates with unexpected postnatal collapse, and newborns with stroke. Preterm HIE: Therapeutic hypothermia shows a good safety profile in clinical studies, and no adverse effects were noted in the preterm fetal animal model. Recently, it has been shown that mild hypothermia in preterm newborns with necrotizing enterocolitis (NEC) and multiple organ dysfunction syndrome (MODS) does not increase mortality, bleeding, infection, or need for inotropes in cooled newborns. A pilot study (NCT00620711) is currently recruiting newborns of > 32 but < 36 weeks gestation with standard criteria for HIE. Postnatal Collapse: The postnatal collapse (PNC) is a rare (0.03–0.5/1000 live births) but life-threatening hypoxic-ischemic event. No clinical trials of therapeutic hypothermia have specifically addressed to PNC. Nevertheless, a beneficial effect of brain cooling is expectable, and it has been proposed to include in brain hypothermia trials the infants with PNC fulfilling the entry criteria for HIE. Stroke: Perinatal arterial ischemic stroke is the most common cause of cerebral palsy (CP) in term and near-term newborn. In a systematic review and meta-analysis of animal studies of focal cerebral ischemia, hypothermia reduced the infarct size by 44%. No specific neuroprotective interventions are available for the management of acute perinatal stroke. Hypothermia may decrease seizures in newborns with encephalopathy and a focal infarct, potentially improving the long-term outcome for these infants. Concluding remarks: Future studies of therapeutic hypothermia should include the categories of newborns excluded from the published clinical trials, that is infants <36 weeks gestation, PNC or stroke, or admitted outside of the established 6-hour window, and with encephalopathy not imputable to HIE. New entry criteria will allow significant number of newborns to benefit from the treatment.

Neonatal Seizures

Neonatal seizures are a common problem encountered or suspected by those caring for neonates. The estimated incidence of newborns affected is between 0.1% to 0.5%. Because several causes of seizures in newborns require rapid recognition and treatment to prevent further injury, early recognition is important. Seizures in newborns frequently have more subtle clinical manifestations than in older children. Electroencephalographic seizures without clinical signs present additional diagnostic and therapeutic challenges. This article reviews the various seizure types, etiologies, diagnostic modalities, and treatment options for neonates with seizures and seizure-like episodes.