Prediction of Future Epilepsy in Neonates With Hypoxic-Ischemic Encephalopathy Who Received Selective Head Cooling.

Epilepsy outcomes after therapeutic hypothermia for neonates with hypoxic-ischemic encephalopathy are understudied. The authors used multivariable logistic regression to predict epilepsy in neonates after selective head cooling. Sensitivity analyses used magnetic resonance imaging (MRI) and electroencephalogram (EEG) interpretations by different clinicians. Fifty neonates had 2-year follow-up. Nine developed epilepsy. Predictors included pH ≤6.8 on day of birth (adjusted odds ratio [OR] 19 [95% confidence interval (CI) 1-371]), burst suppression on EEG on day 4 (8.2 [1.3-59]), and MRI deep gray matter injury (OR 33 [2.4-460]). These factors stratify neonates into low (0-1 factors; 3% [0%-14%] risk), medium (2 factors; 56% [21%-86%] risk), and high-risk groups (3 factors; 100% [29%-100%] risk) for epilepsy. The stratification was robust to varying clinical interpretations of the MRI and EEG. Neonates with hypoxic-ischemic encephalopathy who undergo selective head cooling appear at risk of epilepsy if they have 2 to 3 identified factors. If validated, this rule may help counsel families and identify children for close clinical follow-up.

Therapeutic hypothermia in neonates and selective hippocampal injury on diffusion-weighted magnetic resonance imaging.

BACKGROUND: Hippocampal injury is most often observed in conjunction with basal ganglia injury after hypoxia-ischemia in term newborns. Objective was to determine perinatal characteristics leading to selective hippocampal injury vs basal ganglia injury on diffusion-weighted imaging in term encephalopathic infants following intrapartum hypoxia-ischemia treated with selective head cooling and to correlate specific injury to subsequent neurodevelopmental outcome. METHODS: Retrospective chart review of obstetric and/or perinatal risk factors and patient characteristics in term infants treated with selective head cooling. All infants met standard enrollment criteria for cooling. MRI was obtained at a median of 7 days of life. Abnormal outcome was defined as spastic quadriplegia, cognitive delay, both, or death. RESULTS: Fifty-seven infants were included for analysis. Diffusion-weighted imaging findings included normal (n = 31), basal ganglia injury (n = 16), and selective hippocampal injury (n = 10). No differences in gestational age, birth weight, sex, or labor complications between groups. More infants in the basal ganglia vs hippocampal group required delivery room cardiopulmonary resuscitation (P = 0.05), exhibited persistent severe acidosis, severe amplitude electroencephalography suppression, and encephalopathy at birth (P < 0.05). Abnormal neurodevelopmental outcome or death was observed in 88% vs 10% of infants in the basal ganglia vs the hippocampal group, respectively (P = 0.0001). CONCLUSIONS: Infants with hippocampal injury on diffusion-weighted imaging recovered from an intrapartum asphyxial insult more rapidly as reflected by an earlier correction of acid-base status, were less likely to need cardiopulmonary resuscitation, and were less severely encephalopathic. These findings highlight the exquisite vulnerability of the hippocampus to acute hypoxia unaffected by selective head cooling, whereas the normal appearance of the basal ganglia in these infants suggests a neuroprotective effect of cooling.

Amplitude electroencephalogram characterization in preterm infants undergoing patent ductus arteriosus ligation.

BACKGROUND: Recent studies suggest an increased risk of neurodevelopmental impairment following patent ductus arteriosus surgical ligation. The mechanisms are unclear, but intraoperative stress or pain may contribute. The objectives of this study were to determine if pain, evidenced by an increase in heart rate and blood pressure, during patent ductus arteriosus ligation would be accompanied by an increase in amplitude-integrated electroencephalogram (aEEG) voltage. METHODS: This was an observational, pilot study of infants born at 22.6-35.1 weeks with patent ductus arteriosus requiring surgical ligation. The aEEG was recorded prior to, during surgery, and for 2 hours following surgery. Mean heart rate, blood pressure, and aEEG voltage were analyzed for each recording period. RESULTS: Seventeen preterm infants were studied at a mean postmenstrual age of 26.6 weeks. Following anesthetic induction, aEEG became suppressed and remained suppressed during the postoperative period. Heart rate and blood pressure increased significantly intraoperatively. The aEEG voltage did not increase with an increase in heart rate. Infants received between 3.7-47 µg/kg of fentanyl. CONCLUSIONS: There was no correlation between aEEG voltage and vital sign changes. aEEG is not a useful tool as a marker of pain during patent ductus arteriosus ligation, rather a more standardized approach to pain management should be considered.

Changing pattern of perinatal brain injury in term infants in recent years.

Perinatal brain injury in term infants remains a significant clinical problem. Recently a change appears to have occurred in the pattern of such injuries. We sought to characterize the incidence, etiology, clinical manifestations, and outcomes of these injuries. A retrospective chart review identified clinical characteristics of neuroimaging, electroencephalography, and placental pathologic findings. Perinatal depression was defined as hypotonia and the need for respiratory support. From January 2004-December 2009, 29,597 term deliveries occurred. Brain injuries in 33 infants (live term births) included hypoxic-ischemic encephalopathy (n = 8; 0.27/1000), subdural hemorrhage (n = 10; 0.34/1000), intraventricular/intraparenchymal hemorrhage (n = 5; 0.17/1000), and focal cerebral infarctions (n = 4; 0.14/1000). Thirteen of 33 infants (39%) were triaged to a regular nursery. Delayed presentations included apnea (n = 6), desaturation episodes (n = 3), and seizures (n = 4). Twenty of 33 (61%) were admitted directly to the neonatal intensive care unit because of perinatal depression or evolving hypoxic-ischemic encephalopathy. Clinical signs included seizures (n = 12) and apnea (n = 2). Nine of 19 manifested electroencephalographic seizures. Pathology included chorioamnionitis (n = 7) and fetal thrombotic vasculopathy (n = 5). The latter was associated with focal cerebral infarctions in 3/4 cases. Most cases attributable to perinatal brain injury, except for evolving hypoxic-ischemic encephalopathy, are not identified according to any perinatal characteristics until the onset of signs, limiting opportunities for prevention.

Delayed onset of sleep-wake cycling with favorable outcome in hypothermic-treated neonates with encephalopathy.

OBJECTIVE: To determine whether hypothermia modulates acquisition of sleep-wake cycling in term neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE) and the relationship to outcome. STUDY DESIGN: Twenty-nine term infants with moderate to severe HIE treated with selective head cooling were evaluated. All were monitored with amplitude-integrated electroencephalography during and video electroencephalography immediately after hypothermia for ≥72 hours. Electroencephalograpic data were analyzed for background and sleep-wake cycling. Abnormal outcome included death or severe global neurodevelopmental disability ≥18 months. RESULTS: Acquisition of sleep-wake cycling was noted in nine infants by 72 hours, in 13 by 96 hours, 19 by 120 hours, and 22 by 144 hours. Presence of sleep-wake cycling was associated with normal outcome, that is, 14 of 22 (64%), versus abnormal outcome, that is, none of seven without sleep-wake cycling (P = .006). The presence of sleep-wake cycling by 120 hours had a positive predictive value of 68% and negative predictive value of 90%. Magnetic resonance imaging abnormalities were related to onset of sleep-wake cycling. CONCLUSIONS: Although onset of sleep-wake cycling is markedly delayed in term neonates with moderate to severe HIE treated with hypothermia, approximately 65% with acquisition of cycling have a normal outcome. Sleep-wake cycling is an important additional tool for assessing recovery in term infants with moderate to severe HIE treated with hypothermia.

Chain of Brain Preservation--a concept to facilitate early identification and initiation of hypothermia to infants at high risk for brain injury.

BACKGROUND: Therapeutic hypothermia has been associated with improved outcomes in term infants particularly in those who present with moderate hypoxic-ischemic encephalopathy (HIE). However, in the three major studies the time to initiate cooling was at approximately 4.5 postnatal hours. OBJECTIVE: To determine in term infants who meet criteria for therapeutic hypothermia whether specific clinical and/or biochemical parameters might identify those high risk infants destined for abnormal neurodevelopmental outcome even sooner than is currently possible. DESIGN/METHODS: Retrospective chart review for the following parameters: gestational age, birth weight, sex, labor complications, mode of delivery, 10 min Apgar≤3, cardio-pulmonary resuscitation in the delivery room, cord arterial pH and base deficit, initial postnatal pH and base deficit obtained within 1h, aEEG, Sarnat staging and seizures at enrollment. Abnormal outcome included death and neurodevelopmental deficits. RESULTS: At a single tertiary care center in a metropolitan area, 45 term infants with moderate to severe HIE were treated with selective head cooling initiated at a mean of 4.69±0.79 h of life; 43/45 (96%) were outborn. Five (11%) infants died and of survivors 26 (58%) are normal and 14 (31%) infants are abnormal at follow-up ranging from 12 to 26 months. Infants with abnormal vs. normal outcome were of comparable gestational age, birth weight with no differences in any parameters between groups except that in infants with abnormal vs. normal outcome the postnatal pH obtained within the first postnatal hour was lower, i.e. 6.87±0.15 vs. 7.00±0.22 (p=0.02) and abnormal infants were more likely to present with severe encephalopathy, i.e. 15/19 (79%) vs. 6/26 (23%) (p=0.0002) and clinical seizures, i.e. 14/19 (74%) vs.10/26 (38%) (p=0.03) on admission. CONCLUSIONS: High risk infants who become candidates for therapeutic hypothermia and ultimately have an abnormal outcome may be identified by an additional early postnatal biochemical marker, i.e. the presence of profound metabolic acidosis. An earlier induction of hypothermia that currently occurs particularly in infants with severe encephalopathy may potentially improve outcome. Given that most infants are outborn, a time sensitive education metaphor termed Chain of Brain Preservation may facilitate early recognition of high risk infants and thus earlier treatment.

Restricted diffusion in the corpus callosum in hypoxic-ischemic encephalopathy.

Restricted diffusion within the splenium of the corpus callosum was described in various conditions, but is not a prominent finding in magnetic resonance imaging after neonatal hypoxic-ischemic encephalopathy. Perinatal characteristics were reviewed in 42 term neonates with hypoxic-ischemic encephalopathy treated with selective head cooling. Neonatal images of 34 infants were reviewed. Ten of 34 (29%) infants demonstrated restricted diffusion changes within the splenium of the corpus callosum, with a significantly higher incidence of death or severe developmental delay, compared with infants without changes in the splenium of the corpus callosum (n = 24) (P = 0.002). The positive predictive value of changes in the splenium of the corpus callosum regarding poor outcomes or death was 90%. Changes in the splenium of the corpus callosum were also associated with lower birth weights, larger base deficits in cord arterial gas, and more severe encephalopathy during enrollment in selective head cooling. Restricted diffusion within the splenium of the corpus callosum of term infants with hypoxic-ischemic encephalopathy is often associated with extensive brain injury, and in these circumstances appears to be an early neuroradiologic marker of adverse neurologic outcomes.

Stimulus-induced seizure in sick neonates--novel observations with potential clinical implications.

Stimulus-induced seizure is a well-described entity in children and adults and is often associated with severe epilepsy and neurologic impairment. The occurrence and clinical expression of stimulus-induced seizure in three sick neonates is described. The cohort comprised 26 neonates undergoing continuous video-electroencephalography (vEEG) monitoring between July and December 2007. Three cases (11.5%) of stimulus-induced seizure were identified. The underlying injury included stroke (n = 2) and intraventricular hemorrhage (n = 1). Seizures were induced by physical stimuli such as stroking the forehead, movements, (i.e., starting to feed), and one during endotracheal suctioning. Stimulus-evoked electrographic patterns have been reported in neonates with brain injury; however, these events appear to be more common than previously thought, especially with the abundance of subclinical seizures observed in these patients. These observations stress the usefulness of vEEG monitoring and importance of care to avoid unnecessary stimuli in at-risk neonates.

Seizures are common in term infants undergoing head cooling.

Selective head cooling was used to treat infants at risk of developing encephalopathy within 6 hours as part of a practice plan. Amplitude-integrated electroencephalography and raw, single-channel electroencephalography tracings were performed continuously during cooling. Routine electroencephalography was performed intermittently during, and video electroencephalography immediately after, selective head cooling. Magnetic resonance imaging was performed at the end of week 1. We sought a better delineation of the occurrence and timing of clinical and electrographic seizures during selective head cooling. Twenty term infants are described. Eleven received chest compressions, all at pH <7. Upon admission, encephalopathy was characterized clinically as moderate (n = 13) or severe (n = 7), and by amplitude-integrated electroencephalography as moderate (n = 8), severe (n = 6), or indeterminate (n = 6). Clinical seizures (n = 18) were most prominent on day 1. Amplitude-integrated electroencephalography seizures (n = 9) were evident upon admission and on day 1 (n = 19), and were continuous between 24-36 hours (n = 9). Amplitude-integrated electroencephalography seizures were confirmed by routine electroencephalography. Magnetic resonance imaging was abnormal in nine infants, with predominantly bilateral involvement of the basal ganglia (n = 8). Magnesium was at

MELAS with A3243G mutation presenting with occipital status epilepticus.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disorder commonly caused by the A3243G mutation. We report a patient who initially presented with visual hallucinations, headaches, and nonconvulsive status epilepticus originating in left occipital lobe who subsequently progressed to have multifocal seizures. His magnetic resonance imaging (MRI) showed subtle T2 hyperintensity at first presentation that subsequently fully resolved. He then had more typical diffusion restriction not conforming to vascular territories. Evolution of his neuroimaging and electroencephalogram (EEG) is discussed with a brief review of literature. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes should be suspected early with occipital lobe seizures.

Amplitude-integrated electroencephalography in the NICU: frequent artifacts in premature infants may limit its utility as a monitoring device.

BACKGROUND: Amplitude-integrated electroencephalography has become an important tool for assessing cortical status noninvasively. Newer units have the additional feature of visualizing the raw electroencephalogram, which has resulted in the identification of frequent artifacts. OBJECTIVE: To highlight the problem of artifacts and to introduce caution when using the amplitude-integrated electroencephalography technique to assess cortical function in the premature population. METHODS: Ten premature infants were evaluated. Compressed amplitude-integrated electroencephalography recordings were made by using a pair of standard electroencephalogram electrodes attached to the scalp frontotemporal areas. Impedance was maintained at <10 kOmega. Continuous amplitude-integrated electroencephalography recordings were performed for at least 60 minutes on several occasions in the first month. Artifacts were identified as follows: large amplitude difference between the wave peaks and troughs, a jagged appearance to wave peaks and troughs, and large deflections of the overall tracing in either a positive or negative direction from baseline. RESULTS: Forty-eight amplitude-integrated electroencephalography recordings were reviewed. Of 1683 total segments analyzed, 529 (31.4%) were categorized as normal brain waves, 1013 (60.2%) as artifacts, and 142 (8.4%) as indeterminate. Generally, when the amplitude-integrated electroencephalography tracing is of modest amplitude, normal brain waves predominated, whereas with upward spikes in amplitude the accompanying raw electroencephalogram was classified as artifact. CONCLUSIONS: Artifacts contribute substantially to the amplitude-integrated electroencephalography tracing, rendering it problematic as an assessment tool in premature infants. Artifacts may be influenced by muscle activity, electrode positioning, and application techniques. Caution is recommended when using amplitude-integrated electroencephalography as an assessment tool in this population.

Chiari malformation presenting as a focal motor deficit. Report of two cases.

Chiari malformations may present with a wide range of symptoms and signs. Nevertheless, focal foot weakness as a presentation of a Chiari malformation has not been described in the pediatric neurosurgical literature. Two children with Chiari malformations and holocord syringomyelia presented with manifestations of a supposed isolated lumbar radiculopathy. Neurological deficits completely resolved after decompressive suboccipital craniectomy and cervical laminectomy. These cases emphasize the importance of imaging the entire craniospinal axis and avoidance of therapeutic intervention specifically aimed at a radiculopathic process when initial imaging fails to show a structural abnormality at the spinal level of deficit. The possible pathophysiological origins for this unusual presentation are discussed. Based on the experience gained with these patients, recommendations are made regarding the diagnostic workup and management of this entity in children presenting with focal deficits that are not supported by imaging of the affected root levels. Chiari malformations may rarely masquerade as lower motor and sensory deficits, and appropriate treatment may result in excellent recovery of function.

Apneic seizures: a sign of temporal lobe hemorrhage in full-term neonates.

Intracranial hemorrhage is a common cause of neonatal seizures in full-term infants. However, only some infants with intracranial hemorrhage come to clinical attention. A right temporal lobe hemorrhage with resulting apneic seizures was described previously in one neonate. In this case report, we review three full-term male neonates with no significant perinatal complications who presented with apneic events and temporal lobe hemorrhage. One neonate had apnea as the sole manifestation of a seizure that was confirmed electrographically. One neonate had motor manifestations of seizures, in addition to apnea, that were confirmed as seizures electrographically. The third neonate had pure apneic events before initiation of electroencephalogram monitoring which were presumed to be seizures, because the electroencephalogram demonstrated epileptiform abnormalities. At follow-up, all three children were neurodevelopmentally normal. This case report emphasizes that, although uncommon, full-term neonates may present with apnea as the initial manifestation of temporal lobe hemorrhage. Because apnea could be a manifestation of a seizure, continuous electroencephalogram monitoring should be considered in a full-term neonate with unexplained apnea.