Diagnosis Of Neonatal Seizures Research Articles

Chikungunya in a newborn

Vertical transmission of Chikungunya has been described in neonates but postnatal chikungunya has rarely been reported. We report a neonate from South India, who presented with apnea, seizures and hypotonia followed by typical visceral and peri-oral skin hyperpigmentation. Chikungunya infection was suspected and confirmed by serology (IgM) which was positive in the baby and negative in mother. It is important to remember viral infections in the differential diagnosis of neonatal seizures and apnea.

Fetal Onset Ventriculomegaly and Subependymal Cysts in a Pyridoxine Dependent Epilepsy Patient

Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene encoding α-aminoadipic semialdehyde dehydrogenase. The classic clinical presentation is neonatal seizures responsive only to pyridoxine therapy. White matter abnormalities, corpus callosum agenesis or hypoplasia, megacisterna magna, cortical dysplasia, neuronal heterotopias, intracerebral hemorrhage, and hydrocephalus in neuroimaging have been reported in patients with PDE. We report a new patient with asymmetric progressive ventriculomegaly noted on fetal sonography at 22 weeks' gestation. Postnatal brain sonography on day 1 and MRI on day 5 confirmed bilateral asymmetric ventriculomegaly caused by bilateral subependymal cysts. Intractable seizures at age 7 days initially responded to phenobarbital. Markedly elevated urinary α-aminoadipic acid semialdehyde levels and compound heterozygous mutations in the ALDH7A1 gene (c.446C>A/c.919C>T) confirmed the diagnosis of PDE caused by ALDH7A1 genetic defect. Despite the presence of structural brain malformations and subependymal cysts, PDE should always be included in the differential diagnosis of neonatal seizures that are refractory to treatment with antiepileptic drugs.

Diagnosing Neonatal Seizures and Status Epilepticus

Continuous electroencephalographic (CEEG) monitoring is often applied in the Neonatal Intensive Care Unit to aid in the diagnosis and management of seizures. Neonatal seizures are particularly difficult to identify on the basis of clinical observation alone; diagnosis is greatly facilitated by CEEG monitoring. There is building evidence to suggest which neonates are at highest risk for seizures, and how CEEG can aid diagnosis. For the neurophysiologist, the unique features of neonatal seizures can distinguish them from nonictal patterns. These features include duration, location, morphology, and evolution. At the extreme, very frequent or prolonged neonatal seizures constitute status epilepticus. There is no consensus definition for neonatal status epilepticus, although the proposed criteria share some features. This article reviews available evidence to guide the application and interpretation of CEEG in the diagnosis of neonatal seizures and status epilepticus.

Neonatal Seizures and Status Epilepticus

Neonatal seizures are common, often require EEG monitoring for diagnosis and management, may be associated with worse neurodevelopmental outcome, and can often be treated with existing anticonvulsants. A neonatal electrographic seizure is defined as a sudden, repetitive, evolving, and stereotyped event of abnormal electrographic pattern with amplitude of at least 2 μV and a minimum duration of 10 seconds. The diagnosis of neonatal seizures relies heavily on the neurophysiologist's interpretation of EEG. Consideration of specific criteria for the definition of a neonatal seizure, including seizure duration, location, morphology, evolution, semiology, and overall seizure burden, has utility for both the clinician and the researcher. The importance of EEG in the diagnosis and management of neonatal seizures, the electrographic characteristics of neonatal seizures, the impact of neonatal seizures on outcome, and tools to aid in the identification of neonatal seizures are reviewed.

Instantaneous frequency based newborn EEG seizure characterisation

The electroencephalogram (EEG), used to noninvasively monitor brain activity, remains the most reliable tool in the diagnosis of neonatal seizures. Due to their nonstationary and multi-component nature, newborn EEG seizures are better represented in the joint time-frequency domain than in either the time domain or the frequency domain. Characterising newborn EEG seizure nonstationarities helps to better understand their time-varying nature and, therefore, allow developing efficient signal processing methods for both modelling and seizure detection and classification. In this article, we used the instantaneous frequency (IF) extracted from a time-frequency distribution to characterise newborn EEG seizures. We fitted four frequency modulated (FM) models to the extracted IFs, namely a linear FM, a piecewise-linear FM, a sinusoidal FM, and a hyperbolic FM. Using a database of 30-s EEG seizure epochs acquired from 35 newborns, we were able to show that, depending on EEG channel, the sinusoidal and piecewise-linear FM models best fitted 80-98% of seizure epochs. To further characterise the EEG seizures, we calculated the mean frequency and frequency span of the extracted IFs. We showed that in the majority of the cases (>95%), the mean frequency resides in the 0.6-3 Hz band with a frequency span of 0.2-1 Hz. In terms of the frequency of occurrence of the four seizure models, the statistical analysis showed that there is no significant difference(p = 0.332) between the two hemispheres. The results also indicate that there is no significant differences between the two hemispheres in terms of the mean frequency (p = 0.186) and the frequency span (p = 0.302).

The diagnosis and treatment of neonatal seizures

The occurrence of neonatal seizures is an important clinical sign indicating brain disorder in neonates. An identification of neonatal seizures is critical in the management of high risk neonates. However, the diagnosis and management of neonatal seizures are challenging, because electroclinical dissociation is an outstanding feature of neonatal seizures. Neonatal seizures are frequently not accompanied by any identifiable clinical symptoms even on close observation, whereas motor phenomena which have been considered to be seizures are not associated with ictal electroencephalography (EEG) correlates. For this reason, neonatal seizures should be diagnosed based on ictal EEG findings and the efficacy of treatment should be evaluated using continuous EEG monitoring. EEG is also useful diagnosing the underlying etiology of neonatal seizures. Although conventional EEG is the gold standard for the diagnosis of neonatal seizures, amplitude-integrated EEG (aEEG) can be considered an option. However, aEEG has substantial limitations. In treatment two aspects must be considered. First, neonatal seizures themselves require emergency therapy and second, etiology-specific therapy is important in order to prevent further brain injury. At present, evidence is limited on the treatment of neonatal seizures. In order to establish effective treatment, studies using continuous EEG/aEEG monitoring and long-term follow-up are necessary. Widespread use of EEG/aEEG is desirable in order to solve several problems in the diagnosis and treatment of neonatal seizures.

Isolated Neonatal Seizures: When to Suspect Inborn Errors of Metabolism

Neonatal seizures are common, and often comprise the first clinical indicator of central nervous system dysfunction. Although most neonatal seizures are secondary to processes such as hypoxic-ischemic injury, infection, or cortical malformations (which are readily identifiable through routine testing and imaging), seizures secondary to inborn errors of metabolism can be much more difficult to diagnose, and thus a high index of suspicion is required. The early diagnosis of inborn errors of metabolism is crucial, considering that many can receive effective treatment (e.g., dietary supplementation or restriction) with favorable long-term outcomes. This review emphasizes the importance of considering inborn errors of metabolism in the differential diagnosis of neonatal seizures, discusses red flags for inborn errors of metabolism as a cause of neonatal seizures, and provides an overview of diagnoses and treatments of inborn errors of metabolism most commonly associated with neonatal seizures.

Approach to seizures in the neonatal period: a European perspective

In the neonatal period, seizures rank among the most common neurological symptoms, often indicating an underlying serious neurological condition. It is remarkable that although new tools have been incorporated into the diagnosis of neonatal seizures, there is no consensus about the therapeutic approach among different doctors and institutions. Hence, although phenobarbital is still considered the initial drug of choice, the protocols reported in the literature show a great variability in the approach to treatment of refractory seizures. We used a questionnaire to gain information regarding the treatment of seizures in the neonatal period in different European institutions. We conclude that phenobarbital is still the initial drug of choice followed by benzodiazepines, except in preterm infants with a birth weight below 1800 g. In refractory seizures, the use of continuous lidocaine infusion is most common. Of note, clinical studies with newer drugs have been mostly performed in the United States but not in Europe.

Interobserver agreement in neonatal seizure identification

Accurate diagnosis of neonatal seizures is critically important and is often made clinically, without EEG (electroencephalography) monitoring. This observational study aimed to determine the accuracy and interobserver reliability of healthcare professionals in distinguishing clinically manifested seizures from other neonatal movements, when presented with clinical histories and digital video recordings only. Twenty digital video recordings of paroxysmal movements in term and preterm infants were selected from a video-EEG database. The movements were categorized as seizure and nonseizure using EEG. Health care professionals (n = 137) from eight neonatal intensive care units (NICUs) were shown the video recordings with additional relevant clinical data, excluding EEG findings. The observers were asked to indicate which movements they considered to be seizure or nonseizure. A multirater Kappa statistic was used to assess agreement between observers and with the true diagnosis. Twenty video clips (11 seizure, 9 nonseizure) were evaluated by 91 doctors and 46 other professionals. The average number of correctly identified events was 10/20. Clonic seizures were correctly identified most frequently (range 36.5-95.6% of observers). Subtle seizures were poorly identified (range 20.4-49.6% of observers). The interobserver agreement (Kappa) for doctors and other health care professionals was poor at 0.21 and 0.29, respectively. Agreement with the correct diagnosis was also poor at 0.09 for doctors and -0.02 for other healthcare professionals. It is often impossible to accurately differentiate between seizure-related and nonseizure movements in infants using clinical evaluation alone. In addition, doctors do not have a higher capacity for discriminating between neonatal paroxysmal events than other health care professionals. Until reliable continuous neurologic monitoring of newborn babies is available, it is likely that some babies with seizures will remain undetected and others with nonseizure movements will continue to be treated with potentially harmful anticonvulsants.

Diagnosis of neonatal seizures

Neonatal seizures are generally not only brief and subtle but also not easily recognized and are usually untreated. In sick neonates, seizures are frequently not manifested clinically but are detected only by electroencephalography (subclinical EEG seizures). This phenomenon of electroclinical dissociation is fairly common in neonates. On the other hand, neonates frequently show clinical behaviors such as stiffening, apnea, or autonomic manifestations that mimic seizures, which is usually associated with underlying encephalopathy and non-epileptic seizures. Therefore, it might be difficult to confirm the diagnosis of neonatal seizures. Early recognition of neonatal seizures is important to minimize poor neurodevelopmental outcomes, including cognitive, behavioral, and learning disabilities, as well as the development of postnatal epilepsy. EEG is a reliable tool in the determination of neonatal seizures. Continuous EEG monitoring is essential for the identification of seizures, evaluation of treatment efficacy, and prediction of the neurodevelopmental outcome. However, there is not yet a wide consensus on the optimal “standard” lead montage for the continuous EEG monitoring.

NEONATAL SEIZURE: ETIOLOGY AND TYPE

Objective Neonates, for many reasons, are at particular risk for the development of seizures, which are a strong predictor of later morbidity and mortality in infants. We undertook this study to determine the incidence, etiologic distribution and neonatal seizure type in neonates with hospital admission over a period of 4 years. Materials and Methods This, a retrospective study of newborns admitted in hospital with a diagnosis of neonatal seizures, was conducted over a 4 year period between March 2001 and March 2005. Data were obtained from hospital records was analyzed using the Chi-square test. Results Of 4541 newborns, admitted to hospital, during the study period, seizures occurred in 110 neonates. The incidence of neonatal seizures was 2.4%; the causes of neonatal seizure were Hypoxic-Ischemic Encephalopathy (HIE) - 36.4%, infections -19.1%, metabolic abnormalities - 7.3%, Intra Cranial Hemorrhage (ICH) - 2.7%, structural disorders - 1.8% and in 32.7% of cases, the cause was unknown. Subtle seizures (39.1%) were the most common type of seizures; and the other types were myoclonic (17.3%), clonic (10.0%), Tonic (7.3%), Generalized Tonic Clonic Seizures (GTCS) (12.7%) and in 13.6% of cases the type of seizure was not mentioned. Mortality rate was 13.6%. Conclusion Health care workers and parents need to be made aware of subtle seizures and the importance of timely and appropriate treatment to decrease any further complications.

Utility of Prolonged Bedside Amplitude-Integrated Encephalogram in Encephalopathic Infants

We hypothesized that prolonged bedside limited-channel amplitude-integrated electroencephalogram (aEEG) monitoring following a standard 1-hour conventional electroencephalogram (cEEG) would increase the detection of subclinical seizures and allow continuous evaluation of the background EEG in neonatal encephalopathy. This may identify complementary roles for these EEG technologies in neonatal units where continuous cEEG monitoring may not be readily available. We prospectively recruited 25 term neonates with a diagnosis of neonatal seizures or encephalopathy. All infants underwent a standard 1-hour cEEG followed by 12 to 24 hours of aEEG monitoring. Data from the aEEG (plus the raw signal) were analyzed by an epileptologist and compared with information obtained from the clinical report of the cEEG. aEEG and cEEG data were available for 24 infants. Results from magnetic resonance imaging (MRI) performed at 7 to 10 days of life were available in 23/24 infants. Background classification on cEEG and aEEG was similar in 83% of patients. Five of 24 infants had normal background on cEEG. Prolonged aEEG detected evolution of background from initially normal to moderately abnormal in an additional four infants. It also detected more subclinical seizures than the 1-hour cEEG in 8/14 infants. Normal background on aEEG and cEEG was associated with normal MRI results, and severe background abnormality (5/24) on both aEEG and cEEG was associated with abnormal MRI results. Data obtained from prolonged aEEG (plus raw EEG) provide similar background activity, enhance seizure detection, and complement standard cEEG in predicting short-term outcomes, based on MRI, in term neonates with seizures or encephalopathy. Limited-channel aEEG technology may provide a pragmatic alternative for longitudinal monitoring of newborn infants with encephalopathy in neonatal units where prolonged video EEG monitoring is not feasible.

Perinatal Arterial Stroke in the Preterm Infant

In term infants there has been an increasing awareness of stroke as part of the differential diagnosis of neonatal seizures and other neurological symptoms. The etiological factors responsible for perinatal cerebral infarction, the clinical presentation, and long-term consequences are diverse. Most perinatal arterial ischemic stroke studies looking at maternal, perinatal, and infant characteristics exclude preterm infants from the population studied. More than 10 years ago, it had already been described that perinatal stroke is not only a disorder of term or near-term infants, however, data about preterm infants suffering from stroke are scarce. It is not clear whether this is due to a lower incidence, a lack of awareness, or a different (sub)clinical presentation. In this review the differences between preterm and full-term infants in incidence, clinical presentation, neuro-imaging findings, vascular distribution, and risk factors are described.

Neonatal encephalitis and white matter injury: More than just inflammation?

In this issue of the Annals, Verboon-Maciolek and coworkers show that human parechovirus (HPeV), specifically HPeV3, is an important cause of neonatal viral encephalitis.1 The six serotypes of HPeVs that are included in the genus Parechovirus are small single-stranded (ss) RNA viruses belonging to the family Picornaviridae.2, 3 These viruses bear many similarities with another and better-known Picornaviridae genus, Enterovirus (EV). Indeed, the genus Parechovirus began with the reclassification of echovirus 21 and 22 as HPeV1 and HPeV2 because of molecular and genetic differences from the remainder of EV. These differences are important because they explain, in part, why the usual polymerase chain reaction (PCR) testing for EV does not detect HPeV. Thus encephalitic infection by HPeV3 has been overlooked in the past, one important point of the current article. (Neonatal encephalitis by other HPeV subtypes is extremely rare and not discussed further.) The encephalitis caused by HPeV3 infection as well as by EV is associated with neonatal seizures and with apparent cerebral white matter injury.1, 4 The current report has important implications concerning the etiology of neonatal viral encephalitis, the differential diagnosis of neonatal seizures, and the pathology and pathophysiology of the white matter injury.

Prognosis of neonatal seizures

Change vs more of the same The economy, stupid Don’t forget health care —James Carville, The War Room Seizures during the neonatal period are relatively common, occurring in approximately 1% of all neonates. Neonatal seizures have long been recognized as an obvious marker of brain dysfunction in newborns. One of the more common questions asked by patients and their pediatrician relates to the long-term prognosis in children with neonatal seizures. For many decades, it has been clear that the etiology of neonatal seizures is critical in determining outcome and prognosis. Infants with transient or correctable metabolic abnormalities, like hypocalcemia, have a favorable outcome, while infants with hypoxic-ischemic encephalopathy (HIE), CNS infections, or brain malformations have a generally unfavorable outcome. Separating out the impact of etiology, clinically obvious seizures, and subclinical seizures seen only on EEG has been a daunting challenge for neonatal neurologists. Twenty years ago, Neurology ® published a landmark study by Mizrahi and Kellaway,1 which brought the traditional clinical diagnosis of neonatal seizures into the modern world of video-EEG monitoring. They studied 415 clinical “seizures” in 71 infants, and found that focal clonic seizures and focal tonic …

Muscle Phosphofructokinase Deficiency With Neonatal Seizures and Nonprogressive Course

Muscle phosphofructokinase deficiency is known to cause childhood-onset exercise intolerance, muscle cramps, and myoglobinuria. Rarely, phosphofructokinase deficiency manifests in infancy as congenital myopathy and arthrogryposis with fatal outcome. Here, the authors report the case of a 2-year-old boy with infantile phosphofructokinase deficiency who presented on the third day of life with intractable seizures. Two of his sisters died in infancy with hypotonia, developmental delay, and seizure disorder of unclear etiology. On follow-up, he has had hypotonia and mild developmental delay. However, he continues to gain developmental milestones, and his seizures are now well controlled on carbamazepine. This presentation suggests expanding the phenotype of muscle phosphofructokinase deficiency to include early-onset neonatal seizures. It is also unusual in the relatively milder course of the infantile form of this disorder. The authors propose that this form of glycogen storage disease be considered in the differential diagnosis of neonatal seizures and early infantile nonprogressive muscle weakness.

Benign neonatal sleep myoclonus mimicking status epilepticus.

Benign neonatal sleep myoclonus is a self-limited movement disorder characterized by neonatal-onset myoclonic jerks only during sleep, abrupt and consistent cessation with arousal, and absence of concomitant electrographic changes suggestive of seizures. It has a good outcome and was included in the differential diagnosis of neonatal seizures. A presumed transient serotonin imbalance and genetic factors may play a role in the pathogenesis of this disorder. We report a case of benign neonatal sleep myoclonus mimicking status epilepticus in an infant with a family history of nocturnal myoclonus, tic disorder, and sleep disturbance. We suggest that this benign entity should be included in the differential diagnosis of status epilepticus during the newborn period.

Convulsiones neonatales: Influencia del patrón electroencefalográfico en su evolución y en la respuesta al tratamiento

Neonatal convulsions continues being motive for multiple controversies: the diagnosis only by clinical approaches, the necessity to confirm with EEG record and their treatment and control. To establish the incidence of type of clinical neonatal seizures and the correspondence of these to the EEG trace background and the EEG epileptic activity, the underlying etiology, the response to antiepileptic treatment, and their prognosis. Retrospective study of admitted newborns with the diagnosis of neonatal seizures in our hospital, during the period included between January 1993 and October 2001. Some of variables collected were: birth and gestational age, Apgar, clinical pattern, duration of the convulsions, critical and intercritical EEG traced, EEG background, etiological diagnosis, treatment used and response of the same, evolution and neurological state at hospital discharge and at one year of age (corrected age in preterm infants). 74 children were admitted with neonatal convulsion diagnosis, of these only 56 EEG convulsions were confirmed (42% presented subtle seizures, 33.9% tonic, 64.3% clonic multifocal, 10.7% clonic focal, and 16.1% myoclonic multifocal). 55.4% of the infants had 2 or more types of clinical convulsions, 25% of all had an epileptic state, and 42.9% had at some time of the EEG record, electroclinical dissociation. The more frequent critical EEGs abnormalities was multifocal discharges (64.3%), and together with the focal discharges of low frequency had significant (p<0.01) worse pharmacological control, and also unfavourable outcome. The infants having had EEGs background moderately and markedly abnormal showed unfavourable outcome in 72.2% and 100% respectively, while it was only in 15.4% of the infants who had EEGs background normal or lightly abnormal. With the antiepileptic treatment the clinical control of the convulsions was obtained in more than 80% of the cases, while control of the electrical convulsions was only in 62.5%. There was a higher significant association between favourable response to treatment and normal neurological examination at hospital discharge and at 1 year of age. The necessity to confirm by means of EEG record the neonatal clinical convulsions, before and after having established the anticonvulsant treatment, due to the control of electrical convulsions improves their neurological outcome.

Demographic and intrapartum characteristics of term pregnancies with early-onset neonatal seizures.

To compare the demographic and intrapartum factors of term pregnancies in which early-onset neonatal seizures developed with the characteristics of a large, unselected control population. Pregnancies delivered at term (gestational age > or = 37 weeks) in one birthing unit between 1984 and 1995 with a discharge diagnosis of neonatal seizures were identified. Maternal and neonatal charts of these patients were reviewed to confirm the diagnosis of early-onset seizure (EOS) which was defined as a clinical or EEG-diagnosed seizure within 72 hours of life. Demographic and intrapartum factors were compared between these EOS cases and all singleton term pregnancies delivered over the same time period in which there was no EOS. A regression model was then developed to determine factors predictive of EOS. Of 80,561 total deliveries during the 11-year study period, there were 64,340 control and 62 EOS (0.1%) deliveries. Regression modeling identified NICU admission, depressed 1- and 5-minute Apgar scores, and neonatal intubation as predictors of EOS, but not operative vaginal, vaginal breech, or cesarean delivery. Depressed condition at birth and/or the requirement for NICU care was the most important risk associated with early seizures in term infants.

Polysomnography in neonatal seizures

Seizures are one of the most frequent problems in the neonatal period, and are frequently associated with high mortality and morbidity rates. On the other hand, neonatal seizures may represent a first or even the only sign of central nervous system dysfunction. However, establishing the diagnosis of neonatal seizures poses several problems, and clinical observation is not sufficient in many cases. Neonatal polysomnography is a valuable tool both in the diagnostic and in the prognostic assessment of neonatal seizures. The present text reviews some technical aspects related to neonatal polysomnographies, and its usefulness in the area of suspected neonatal seizures. Moreover, some questions are raised regarding rhythmic discharges and their significance as a possible ictal and interictal epileptic pattern in the neonate.