Post-neonatal Epilepsy Research Articles

Commentary on Hewapathirane et al. ( in vivo imaging of seizure activity in a novel developmental seizure model) seizure-induced brain damage: From tadpoles to children

0014-4886/$ – see front matter © 2008 Elsevier Inc. Al doi:10.1016/j.expneurol.2008.05.005 Epilepsy, a condition characterized by repeated, unprovoked seizures, is unfortunately quite common, affecting approximately 1% of the population (Hauser, 1994), Epilepsy is most common in the first year of life and approximately 75% of epilepsy begins during childhood. The underlying mechanisms responsible for this increased excitability during this period of life are not completely understood but are clearly age-dependent. During the early postnatal period, at a time when the immature brain is highly susceptible to seizures (Jensen et al., 1992; Jensen and Baram, 2000; Khazipov et al., 2004), GABA exerts paradoxical excitatory action, indicating that in the young brain enhanced excitability is due to the excitatory rather than inhibitory actions of GABA (Dzhala and Staley, 2003; Khazipov et al., 2004). The lack of an efficient time-locked inhibition, the delayed maturation of postsynaptic GABA(B)-mediated currents and the high input resistance of small and densely packed neurons also facilitates the generation of action potentials and synchronized activities (Gaiarsa et al., 1995; McLean et al.,1996). As the brainmatures, enhanced excitatory neurotransmission may play an additional role in the propensity for the immature brain to seize as there is an overabundance of excitatory receptors (AMPA and NMDA) (Insel et al., 1990; McDonald et al., 1990; Miller et al., 1990; Brennan et al., 1997). With further maturation, axonal collaterals and attendant synapses regress (Swann et al., 1990, 1991). While seizures are common in children there is controversy regarding whether seizures result in neurological sequelae. It is known that neonatal seizures are often associated with long-term neurological consequences including post-neonatal epilepsy, behavioral problems, and mental retardation (Scher et al., 1989, 1993; Brunquell et al., 2002). While it iswidely recognized that the etiologyof the seizures is a primary determinant of outcome, there remains controversy regarding whether the occurrence of seizures themselves in the young children contribute

Development of epilepsy in newborns with moderate hypoxic-ischemic encephalopathy and neonatal seizures

Background: Hypoxic-ischemic encephalopathy (HIE) is one of the most frequent causes of neonatal death or neurological handicaps such as cerebral palsy, mental delay, and epilepsy. Moreover, an acute consequence of HIE are neonatal seizures which can cause an additional brain damage. The neurodevelopmental outcome is known in the mild or severe cases of HIE, but in the moderate conditions the predictivity results, to date, unsatisfying. Objective: The purpose of this prospective study was to appraise the development of post-neonatal epilepsy in a cohort of term infants with moderate HIE and neonatal seizures. Methods: This study considered all newborns admitted to Neonatal Intensive Care Unit of the University of Parma between January 2000 and December 2002 for perinatal asphyxia, then followed by Neonatal Neurology Service. In all patients, neonatal variables such as type of delivery, birth weight, gestational age, Apgar scores, the need for resuscitation and assisted ventilation soon after birth, and arterial-blood pH were analyzed. Results: Ninety-two newborns were enrolled in the study because of perinatal asphyxia. Of these, 27 subjects developed mild HIE, 25 moderate, and five severe HIE. Neonatal seizures were present in 13 subjects with moderate HIE and in all newborns with severe HIE. At the last follow-up, only three infants belonging to patients with severe HIE developed epilepsy. Conclusion: Moderate HIE seems not to be related to post-neonatal epilepsy either if associated or not with neonatal seizures.

Neonatal status epilepticus vs recurrent neonatal seizures

Although most children with status epilepticus have a good prognosis, its effects on newborns are unclear. We compare the neurodevelopmental consequences of recurrent seizures and status epilepticus in newborns. One hundred six newborns with video-EEG-confirmed seizures, consecutively admitted to the neonatal intensive care unit of the University of Parma between January 1999 and December 2004, were enrolled in the study. Fifty-one were preterm and 55 were full-term newborns. Neonatal status epilepticus was defined as continuous seizure activity for at least 30 minutes or recurrent seizures lasting a total of >30 minutes without definite return to the baseline neurologic condition of the newborn between seizures. Neurologic outcome was assessed at 24 months of corrected age. Thirty-six newborns had a normal outcome, 20 died, and 50 presented an adverse outcome. All but 1 of the 26 subjects with neonatal status epilepticus had an adverse outcome. Birth weight, severely abnormal cerebral ultrasound scans, and status epilepticus were independent predictors of abnormal outcome. Depending on gestational age (GA), neonatal status epilepticus seems to be a risk factor of adverse outcome in full-term newborns (GA >or= 37 weeks: odds ratio [OR] 20.312, 95% CI 2.417 to 170.679, p = 0.006), and a risk factor of epilepsy in early preterm and full-term newborns (GA <or= 29 weeks: OR 10.500, 95% CI 1.211 to 91.026, p = 0.033; GA >or= 37 weeks: OR 6.517, 95% CI 1.321 to 32.148, p = 0.021). Newborns with status epilepticus are at high risk of severe neurologic disability and postneonatal epilepsy. This is particularly evident in early preterm and full-term infants.

Preterm infants with video-EEG confirmed seizures: Outcome at 30 months of age

Objective Our aim was to identify early predictors of poor neurodevelopmental outcome and of subsequent epilepsy in very early preterm and late preterm newborns with neonatal seizures. Study design: Fifty-one preterm infants with gestational age (GA) ⩽36 weeks were identified among those admitted to the NICU of University Hospital of Parma between January 1999 and December 2003 and prospectively followed-up. They were subdivided in two Groups: early preterm newborns with a GA ⩽29 weeks and those with GA between 30 and 36 weeks. Selection criteria included multiple digital-video-EEG confirmed neonatal seizures and a follow-up of at least 30 months. Independent variables considered for analysis included neonatal risk factors, etiology and type of seizures, EEG activity, and cerebral ultrasound scan examinations. Results: Ten infants had a favorable outcome, 17 died, and 23 had an adverse outcome. One infant was lost on follow-up. Apgar score at 1 min (O.R. = 15.457, 95% CI: 2.236–106.850, p = 0.006) and severely abnormal background EEG activity (O.R. = 8.298, 95% CI: 1.316–52.301, p = 0.024) were independent predictors of abnormal outcome. Nine infants presented post-neonatal epilepsy. Severely abnormal Cerebral Ultrasound scans were predictive of epilepsy (O.R. = 13.72, 95% CI: 1.959–96.149, p = 0.008). Conclusions: Neonatal seizures in preterm infants are associated to a high rate of mortality and severe morbidity in survivors but no definitive differences between the two groups of preterm infants were found. Risk-factors for development of subsequent epilepsy are strongly related to the underlying brain damage.

Postneonatal epilepsy following amplitude-integrated EEG-detected neonatal seizures

To assess the incidence of postneonatal epilepsy in term infants treated with antiepileptic drugs for neonatal seizure discharges that were detected with amplitude-integrated electroencephalography (aEEG), 206 term infants were monitored using this modality. They received antiepileptic drugs for clinical as well as subclinical neonatal seizures. Follow-up data were analyzed for the development of postneonatal epilepsy and for their neurodevelopmental outcome, assessed at 3, 9, 18 months, and 3 and 5 years of age. A total of 169 (82%) neonates received two or more antiepileptic drugs. Overall mortality was 39% (n = 80). Forty-one of the 126 survivors (33%) were abnormal at follow-up, and 12 of them developed postneonatal epilepsy (9.4%). Eighty-four children survived after hypoxic-ischemic encephalopathy grade II (n = 92), and 6 (7%) developed postneonatal epilepsy. In this subgroup, no postneonatal epilepsy was observed if seizures were controlled within 48 hours after birth and when not more than two antiepileptic drugs were required. Twenty-four children survived after an intracranial hemorrhage (n = 28), and only 1 (4%) developed postneonatal epilepsy. Eleven children survived after perinatal arterial stroke (n = 13), and 2 (18%) developed postneonatal epilepsy. In conclusion, the incidence of postneonatal epilepsy after treatment of clinical and subclinical neonatal seizures detected with continuous amplitude-integrated electroencephalography was 9.4%; This figure is lower than previously reported in children who only received treatment for clinical seizures.

Prognostic value of non-reactive burst suppression EEG pattern associated to early neonatal seizures

Seizures are the most frequent neurological event in newborns and clinical data suggest that etiology is the dominant factor in long term outcome. However, there are consistent background EEG abnormalities associated to neonatal seizures that are usually related to unfavorable outcome as the burst-suppression pattern. The objective of this study was to correlate clinical and EEG features associated to long-term outcome of newborns with non-reactive burst-suppression (BS) EEG. Newborns included in the study were selected from our database and had conceptional age (at the time of first EEG) >37 weeks, EEG recordings with non-reactive BS available for review and clinical follow up. 12 newborns met inclusion criteria, 50% had seizures in the first day of life. Seizures became refractory to treatment in all of them. In 50% the etiology of seizures was considered cryptogenic, 33% had inborn errors of metabolism and 17% had clinical history and neuroimage suggestive of hypoxic-ischemic encephalopathy. The follow-up showed that 7/12 infants deceased, 3 during the first year of life, and one in the neonatal period. All the survivors had severe developmental delay and multifocal neurological impairment. 92% developed refractory epilepsy, 58% were latter diagnosed with West syndrome. The non-reactive BS pattern may appear related to many neonatal neurological disorders and is associated with early and refractory neonatal seizures. It is clearly associated with elevated morbidity and mortality and to the development of post-neonatal epilepsy.