Neonatal seizures: multicenter variability in current treatment practices

Standardized approaches to the treatment of neonatal seizures remain undeveloped. We assessed the type and number of anticonvulsants selected, blood levels attained, and postdischarge anticonvulsant treatment of neonatal seizures among five neonatal intensive care units in the United States between 2000-2003. Almost all of the 480 neonates (94%) with seizures were treated, initially with phenobarbital (82%), lorazepam (9%), phenytoin (2%), other anticonvulsants (1%), or a combination of the first two drugs (6%). While the majority of neonates were treated with one drug (59%), the number of anticonvulsants varied (P<0.0001), as did the peak serum phenobarbital levels (P<0.0001). The majority (75%) of survivors received anticonvulsant treatment after discharge. These neonates were more likely to have had abnormal electroencephalography or brain imaging, or to have needed a second anticonvulsant, compared with neonates whose drug therapy was discontinued. Anticonvulsant therapy is used in the majority of neonates with seizures, mostly with phenobarbital, and treatment is continued beyond discharge. The observed wide therapeutic variability may reflect a lack of standardized diagnostic and treatment approaches, particularly for seizures refractory to initial phenobarbital therapy. Trials of anticonvulsants with long-term neurodevelopmental follow-up are needed to develop evidence-based treatment guidelines.     

Neonatal seizures: characteristics of EEG ictal activity in preterm and fullterm infants

The neonatal EEG remains one of oldest, yet most valuable, diagnostic and prognostic tests in neonates. The goals of this study were to determine the relationships between the morphology, frequency, and distribution of ictal discharges in the neonatal EEG with age, EEG background activity, and etiology. A total of 156 ictal events were evaluated in 11 preterm (PT) and 25 fullterm (FT) infants. Most of the infants had severe abnormalities of background activity although ictal discharges occurred on both normal and abnormal backgrounds. There was a trend for a closer relationship between behavioral changes during the electroencephalographic seizure when the background activity was normal or moderately abnormal than when background activity was severely abnormal. In both PT and FT infants, the most common site of seizure origin was the temporal lobe. FT infants commonly had sharp waves, spikes, sharp and slow waves, and spike and slow waves at the onset of the ictus while rhythmic delta activity was most common in the PT infants. PT infants typically had a regional onset to the ictus whereas FT infants most frequently had a focal onset. Duration of the ictal events was similar in PT and FT infants and a change in morphology or frequency of the discharges was common during propagation of the ictal discharges in both age groups. There was not a clear relationship between onset, morphology, frequency, or propagation patterns and etiology in either the PT or FT infants. Our results demonstrate that while the type of ictal discharge is related to gestational age, there is a rich variety in the onset, morphology, and frequency of the ictal discharges in both PT and FT infants and that neonatal ictal patterns lack a close correlation with underlying pathology.     

Prognostic value of the electroencephalogram in term and preterm infants following neonatal seizures

There is controversy in the literature regarding the prognostic value of the EEG following neonatal seizures. This report reviews the results of a prospective study comparing EEG findings and outcome in 74 term and preterm infants following neonatal seizures. EEGs were evaluated for both background rhythms and epileptiform activity. Outcome was evaluated at an average age of 33 months. Background rhythms were highly correlated with outcome. Low voltage, electrocerebral inactivity and burst suppression EEGs were associated with poor outcomes while normal EEGs were associated with favorable outcomes. Slow, maturationally delayed and asymmetrical EEGs were associated with variable outcomes. The presence of epileptiform activity on the EEG was correlated with adverse outcomes but was not as highly significant as background rhythms. Electroencephalographic seizures, whether associated with clinical manifestations or not, were highly correlated with poor outcomes. The significance of these EEG findings was similar in both term and preterm infants. The study demonstrates that the EEG is predictive of outcome following neonatal seizures.     

Neonatal seizures: diagnosis and treatment

Neonatal seizures are a frequent problem encountered in neonatal nurseries, but their significance is controversial. Some investigators regard newborn seizures as simply epiphenomena and reflective of brain injury, whereas others note associated metabolic and physiologic aberrations suggesting that seizures per se are injurious to the central nervous system. The proper approach to the treatment of neonatal seizures depends on the etiology because treatment differs if seizures are of metabolic, toxic, or structural origin. Most studies reporting the efficacy of anticonvulsant agents neither define the seizure characteristics being treated nor use electroencephalographic documentation of seizure activity. The choice of anticonvulsants has been based on tradition rather than on the proven superiority of one agent over another. Although several anticonvulsants are available, phenobarbital remains the drug most frequently chosen as the initial agent in treatment. The important pharmacologic considerations of anticonvulsants include route of administration, ability to achieve therapeutically efficacious and predictable plasma levels rapidly, drug distribution, the availability and affinity of receptor sites, protein-binding characteristics, effects on brain growth, and cardiovascular toxicities. At the present time, critical questions remain regarding the effects of both seizures and anticonvulsants on the developing central nervous system.     

Neonatal risk factors in preterm infants

This paper highlights the research literature on neonatal risk factors and explores the paradox that these factors present. Clinical and retrospective studies indicate that children who have developmental problems have had birth complications. On the other hand, birth complications do not predict developmental problems. Data from a longitudinal study of preterm infants are presented. A group of 59 preterm infants from English Speaking homes was assessed repeatedly from birth to age 5. A significant percentage of the children performed within the normal range or above, at each assessment period. Obstetrical and postnatal complications were not significantly related to developmental performance at any assessment period yet sickness was not to be dismissed as a risk factor. At age five, all of the children who performed poorly had experienced complications in the neonatal period. Responsive caregiving appeared to be an important factor in modifying and supporting cognitive development.     

Neonatal seizures and their treatment

PURPOSE OF REVIEW: Neonatal seizures continue to present a diagnostic and therapeutic challenge to paediatricians worldwide, and are a worrying sign for both parents and clinicians alike. The present review summarizes recent evidence regarding the diagnosis, aetiology and treatment of neonatal seizures. It is timely because there is new evidence that seizures are damaging to the neonatal brain, and because prolonged electroencephalographic recordings during treatment have provided information that challenges established treatment regimens. RECENT FINDINGS: Neonatal seizures can permanently disrupt neuronal development, induce synaptic reorganization, alter plasticity and "prime" the brain to increased damage from seizures later in life. Phenobarbitone remains the mainstay of treatment and is effective in about one-third of cases; babies who respond tend to have a smaller seizure burden and a relatively normal background electroencephalogram. Their prognosis is better than in those who require second-line treatments. Phenytoin and lignocaine (membrane stabilizing drugs) are probably more effective than any of the benzodiazepines as second line, but very few evaluation studies have been reported. Babies who require second-line treatments are more likely to have hypoxic ischaemic encephalopathy, an abnormal background electroencephalogram and a large seizure burden, and have a worse prognosis than do those who respond to a single agent; most have significant disability at follow up. SUMMARY: The search for an effective antiepileptic regimen in the newborn must continue. Whether better control of neonatal seizures leads to a reduction in neurodisability in childhood cannot be determined until more effective treatments are found. Meanwhile, electroencephalography remains the most useful investigation for diagnosis and prognosis.     

Ictal electroencephalographic findings of neonatal seizures in preterm infants

The aim of this study is to clarify the characteristics of ictal EEG findings of neonatal seizures in preterm infants. Seizures associated with ictal EEG changes were recognized in nine infants with gestational age of less than 37 weeks. Propagation, migration, shifting, changes in morphology of ictal EEG discharges were evaluated. Seizure manifestation was divided into the following categories; motor seizure, apneic seizure, automatic seizure and seizure without clinical symptoms. The types of the seizures were motor seizures in five infants, apneic in two, automatic in one and those without clinical symptoms in five. All seizures were of focal onset. The foci of seizures were temporal in six infants, occipital in two, central in one, and frontal in one. The morphology of ictal discharges was low voltage spikes or sharp waves in six infants, spikes in two, theta waves in one and high-voltage spiky theta in one. The propagation of ictal discharges was focal in five infants and regional in five. The migration of ictal discharges was observed in two infants and a shift in two. There was no clear relation between seizure manifestation and ictal EEG foci, duration of seizures and morphology or propagation of ictal discharges.     

Neonatal seizures in very preterm and very low birthweight infants: mortality and handicaps at two years of age in a nationwide cohort

In a nationwide, prospective survey on very preterm and/or very low birthweight infants (less than 32 weeks of gestational age and/or less than 1500 g birthweight) we studied the outcome at the corrected age of two years of children with neonatal seizures. Of the 1338 infants, originally enrolled in the study, 72 had neonatal seizures; of these 44 died and 11 developed a major handicap. Using a multivariate statistical method, a significantly increased risk of death as well as handicap was found in infants with seizures compared to infants without seizures. Nevertheless, 16 of the 28 survivors with neonatal seizures were considered normal at the corrected age of two years.     

Neonatal protein C: molecular composition and distribution in normal term infants

Protein C (PC) is a vitamin K-dependent serine protease which functions as the central regulatory protein with both anticoagulant and profibrinolytic properties. The PC levels in healthy term newborns are approximately one third of adult levels. Severely decreased levels of PC are seen in sick term and preterm infants. These neonates appear to have an increased incidence of thrombosis. Undetectable levels of PC are found in homozygous PC deficient infants with DIC and purpura fulminans symptoms. In this present study we report the composition and distribution of PC in term newborn and compare the results with adult values. Plasma was obtained from placental cord blood of 20 healthy term (38-42 weeks gestation) infants. PC was immunopurified, run on SDS-PAGE, and immuno-blotted. The composition of the PC molecule in neonatal plasma is identical to that seen in adults. Using densitometry to determine the distribution of the PC components, we observed a 2-fold increase in single chain PC in the neonate as compared to the adult. In the neonate, there was an inverse correlation between the level of total PC antigen and the amount of single chain. These findings suggest the possibility that the processing of PC may be developmentally influenced.     

Neonatal seizures: a reappraisal

Sixty-three infants with neonatal seizures were studied in terms of etiology, seizure type, electroencephalograms, and outcome. Twenty-nine percent were normal when followed for up to five years; twenty-nine percent were brain damaged, and twenty-five percent expired. In spite of improved obstetrical care, the occurrence of neonatal seizures may be associated with significant morbidity and mortality.     

Motor development and sensory processing: A comparative study between preterm and term infants

Infants born preterm and/or with low birth weight may present a clinical condition of organic instability and usually face a long period of hospitalization in the Neonatal Intensive Care Units, being exposed to biopsychosocial risk factors to their development due to decreased spontaneous movement and excessive sensory stimuli. This study assumes that there are relationships between the integration of sensory information of preterm infants, motor development and their subsequent effects.ObjectiveTo evaluate the sensory processing and motor development in preterm infants aged 4–6 months and compare performance data with their peers born at term.MethodThis was a cross-sectional and comparative study consisting of a group of preterm infants (n = 15) and a group of term infants (n = 15), assessed using the Test of Sensory Functions in Infants (TSFI) and the Alberta Infant Motor Scale (AIMS).ResultsThe results showed no significant association between motor performance on the AIMS scale (total score) and sensory processing in the TSFI (total score). However, all infants who scored abnormal in the total TSFI score, subdomain 1, and subdomain 5 presented motor performance at or below the 5th percentile on the AIMS scale.ConclusionSince all infants who presented definite alteration in tolerating tactile deep pressure and poor postural control are at risk of delayed gross motor development, there may be peculiarities not detected by the tests used that seem to establish some relationship between sensory processing and motor development.     

The cavum septi pellucidi in term and preterm newborn infants.

We reviewed cranial sonographic studies done on 108 normal newborn infants to determine the prevalence and variability in size of the cavum septi pellucidi (CSP). Infants were classified according to gestational age by 2-week intervals. At 24 weeks, only four normal scans were identified. Between 26 and 34 weeks, ten consecutive normal scans were used since all infants had a CSP. At 36, 38, and 40 weeks, all normal scans were counted in order to obtain a prevalence estimate. A CSP was seen in all normal infants below 36 weeks of gestational age. At 36, 38, and 40 weeks, only 69%, 54%, and 36%, respectively, had CSPs. There was no significant change in the width, depth, or area of the CSP with age, birth weight, or biparietal diameter. A CSP greater than 0.95 cm in width or greater than 0.81 cm in depth is outside the normal range and may represent anomalous development of the midline structures of the brain.     

Electroencephalography in infants with periventricular leukomalacia: prognostic features at preterm and term age

Cystic periventricular leukomalacia represents the most severe white-matter lesion in preterm infants and its occurrence accounts for most cases of neurologic impairment in these subjects. Electroencephalographic (EEG) findings and their prognostic value in relation to motor and cognitive outcome were investigated in a group of preterm infants affected by different degrees of cystic periventricular leukomalacia. EEG recordings were carried out in the early postnatal period (first 2 weeks of life) on 24 infants and at term age on 29. In the early postnatal period, background EEG abnormalities ("dysmaturity") were significantly more apparent in affected infants than in a control group, and, among infants with cystic periventricular leukomalacia, this parameter related to the occurrence of cerebral palsy; moreover, at the same age, the incidence of abnormal EEG transients seemed to show a correlation with cognitive outcome. At term age, these latter abnormalities were significantly more apparent in neonates with cystic periventricular leukomalacia than in control subjects, but they did not show any prognostic value. In conclusion, these data indicate that, during the early postnatal period, the EEG is a useful diagnostic and prognostic tool for preterm infants with white-matter lesions, whereas at term age, the role of EEG tracings appears secondary.     

Long‐term adherence with psychiatric treatment among patients with psychogenic nonepileptic seizures

We conducted a prospective cohort study, examining long‐term adherence with psychiatric treatment among patients with psychogenic nonepileptic seizures (PNES). Subjects diagnosed with documented PNES were scheduled for 4 psychiatric visits. Survival analysis was performed, and covariates were assessed for association with time to nonadherence using Cox proportional hazard regression analysis. One hundred twenty‐three subjects were recruited and followed for up to 17 months. Eighty percent of subjects attended the first outpatient visit, 42% attended the second, 24% attended the third, and only 14% remained adherent through the fourth visit. Two covariates were associated with nonadherence: (1) a prior diagnosis of PNES (hazard ratio 1.57, P‐value .046); (2) a lower score on the Brief Illness Perception Questionnaire (BIPQ), signifying lower concern about one's illness (hazard ratio 0.77 for every 10‐point increment on the 80‐point scale, P‐value .008). Adherence with psychiatric treatment among patients with PNES is initially reasonably good but worsens rapidly over visits 2‐4. Risk factors for nonadherence include a history of a prior diagnosis of PNES, and a lower level of concern about the illness as assessed by a lower score on the BIPQ.     

Neonatal seizures: electroclinical dissociation.

Electroclinical dissociation is a phenomenon in which the clinical component of a seizure occurs at times with or without an electrical correlate. The epidemiology of this observation was studied in a neonatal intensive care unit from July, 1983 to December, 1988. Infants demonstrating electroclinical dissociation were compared to those having exclusively electroclinical seizures. Sixteen percent of infants with electrographically-confirmed seizures and 19% of 243 analyzed seizures demonstrated electroclinical dissociation. The two groups revealed very few differences with respect to perinatal factors, etiology, and outcome. The subsequent electroencephalographic background was more disturbed in the electroclinical dissociation group, but did not correlate with clinical outcome. Extremity movements occurred at a statistically significant higher rate during electroclinical seizures. Electroclinical dissociation seizures arise from foci not consistently reflected in surface electrodes.