Michael J. Painter

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.

BACKGROUND Seizures occur in 1 to 2 percent of neonates admitted to an intensive care unit. The treatment is usually with either phenobarbital or phenytoin, but the efficacy of the two drugs has not been compared directly. METHODS From 1990 to 1995, we studied 59 neonates with seizures that were confirmed by electroencephalography. The neonates were randomly assigned to receive either phenobarbital or phenytoin intravenously, at doses sufficient to achieve free plasma concentrations of 25 microg per milliliter for phenobarbital and 3 microg per milliliter for phenytoin. Neonates whose seizures were not controlled by the assigned drug were then treated with both drugs. Seizure control was assessed by electroencephalographic criteria. RESULTS Seizures were controlled in 13 of the 30 neonates assigned to receive phenobarbital (43 percent) and 13 of the 29 neonates assigned to receive phenytoin (45 percent; P=1.00). When combined treatment is considered, seizure control was achieved in 17 (57 percent) of the neonates assigned to receive phenobarbital first and 18 (62 percent) of those assigned to receive phenytoin first (P=0.67). The severity of the seizures was a stronger predictor of the success of treatment than was the assigned agent. Neonates with mild seizures or with seizures that were decreasing in severity before treatment were more likely to have their seizures end, regardless of the treatment assignment. CONCLUSIONS Phenobarbital and phenytoin are equally but incompletely effective as anticonvulsants in neonates. With either drug given alone, the seizures were controlled in fewer than half of the neonates.

Cerebrovasculopathy following irradiation in childhood

Symptomatic intracranial vasculopathy developed in four patients following irradiation for central nervous system tumors. All the patients presented with a stroke-like picture from 2 to 22 years after the completion of radiotherapy. Two of the patients showed abnormalities on arteriography consisting of narrowing of the supraclinoid portion of the internal carotid artery and the adjacent proximal anterior and middle cerebral arteries. Although the risks of radiotherapy for central nervous system tumors of malignant potential are outweighed by potential benefit, the risks should be carefully considered in cases of tumors with little or no malignant potential.

Uncoupling of EEG-clinical neonatal seizures after antiepileptic drug use

A prospective study of the efficacy of seizure cessation by phenobarbital versus phenytoin administration utilized both clinical and electroencephalographic expressions of seizure behaviors. The phenomenon of uncoupling was defined as the persistence of electrographic seizures despite the suppression of >or=50% clinical seizures after either one or both antiepileptic drugs use. Fifty-nine neonates (25 to 43 weeks estimated gestational age) with electrically-confirmed seizures were assigned to either of two drugs and continuously monitored over a 24-hour period. Nine of the fifty-nine patients had only electrographic seizure expression both before and after drug administration. Of the remaining 50 patients who had both electrical and clinical seizure expression before treatment, 24 infants responded to the first choice of an antiepileptic drug with no further seizures. Fifteen of the remaining 26 infants (58%) with persistent seizures after treatment had uncoupling of electrical and clinical expressions of seizures; no difference in the uncoupling effect was noted for neonates who were treated with either antiepileptic drug or based on prematurity or gender. Serial electroencephalographic monitoring helps document continued electrographic seizure expression after antiepileptic drug use, following complete or partial suppression of clinical seizure behaviors.

Ictal and interictal electrographic seizure durations in preterm and term neonates.

Summary: The effect of gestational age on neonatal ictal and interictal durations has not been investigated. Sixty‐eight neonates with 644 electrographic seizures were identified retrospectively. Thirty‐five full‐term (FT) neonates were compared with 33 preterm (PT) neonates. Eighteen older preterm infants (OPT) [>31 weeks estimated gestational age (EGA)] were also compared with 15 young preterm infants (YPT) of ≤31 weeks EGA. Ictal/ interictal durations were calculated for the total cohort with and without status epilepticus (SE). Statistical analyses were two‐tailed t tests, chi‐square calculations, and one‐way analysis of variance (ANOVA) with Duncans multiple‐range test. Eleven of 35 (33%) FT had SE as compared with 3 of 33 (9%) PT (chi‐square = 7.8, p < 0.05). The mean ictal duration was 14.2 min for FT infants as compared with 3.1 min for PT infants (p < 0.01); only borderline differences were noted after those with SE were excluded. Interictal durations were longer for OPT than YPT (p < 0.05). By ANOVA and Duncans multiple‐range tests, group differences included longer mean ictal durations for FT infants as compared with OPT infants (p = 0.06, ANOVA; p < 0.05, Duncans), and longer mean interictal durations for FT infants versus OPT and OPT versus YPT (p = 0.02, ANOVA; p < 0.05, Duncans). More developed neuronal networks result in longer ictal durations in FT than in PT neonates, including FT infants with SE. Inhibitory networks responsible for longer interictal periods are more dominant in OPT infants than in YPT infants, reflecting maturational changes that suppress seizure activity during the latter part of the third trimester before the infant reaches an FT corrected age.

Cause of hearing loss in the high-risk premature infant

Bilateral hearing loss occurred in 9.7% of infants who survived despite very low birth weight (less than or equal to 1500 gm), 16.7% of infants who survived neonatal seizures, and 28.6% of infants who survived both low birth weight and neonatal seizures. All neonates received treatment in a single neonatal intensive care unit between 1976 and 1980. Twenty-two of 36 hearing-impaired children were normal physically and mentally, with IQ scores of greater than or equal to 85. Significant neonatal predictors of hearing loss in high-risk premature infants (less than or equal to 36 weeks gestation), as determined by multivariable testing, were prolonged respirator care, high serum bilirubin concentration, and hyponatremia. Exchange transfusions were associated with a decreased risk of hearing loss.

Neonatal asphyxia. II. Neonatal mortality and long-term sequelae

Neonatal asphyxia, defined in this study as delay of greater than 1 minute in onset of spontaneous respiration at birth, occurred in 1% of 13,221 live-born infants of birth weight greater than 500 gm between 1970 and 1971. Seventy-five (56%) of 133 asphyxiated infants survived the neonatal period. Survival was directly related to gestational age. The 65 survivors of asphyxia available for study were seen at a mean age of 4.8 years to determine the incidence and extent of neurologic and developmental abnormalities. Twelve children (18.5%) had severe impairment: nine had both neurologic and intellectual handicaps, two had neurologic impairment alone, and one had intellectual impairment alone. The incidence and severity of impairment were not related to gestational age. Postasphyctic seizures were associated with poor outcome.

Noninvasive continuous monitoring of cerebral oxygenation periictally using near-infrared spectroscopy: a preliminary report.

Summary: Purpose: To report on the use of near‐infrared spectroscopy (NIRS) to examine the changes in cerebral oxygenation in the periictal period in patients with seizures.

Building a Bridge from Fragmentation to Accountability — The Prometheus Payment Model

What kind of payment system could promote and sustain high-value care and motivate the development of accountable care organizations? Francois de Brantes, Meredith Rosenthal, and Dr. Michael Painter describe the Prometheus Payment model.

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.

Phenobarbital and phenytoin in neonatal seizures Metabolism and tissue distribution

Loading doses of 15 to 20 mg per kilogram of both phenobarbital and phenytoin, administered intravenously, are necessary in the newborn to achieve rapid therapeutic plasma anticonvulsant levels. Maintenance doses of 3 to 4 mg per kilogram of both agents will maintain therapeutic levels. Phenytoin is, however, not predictably absorbed by the oral route. Brain: plasma ratios were 0.71 2 0.21 for phenobarbital and 1.28 ± 0.32 for phenytoin, which are in general agreement with reported adult values. The brain: plasma ratio of phenobarbital increased with gestational age. Phenytoin was found in higher concentration in gray matter, whereas phenobarbital was equally distributed between gray and white matter.