Neonatal Seizures 

The most prominent feature of neurologic dysfunction in the neonatal period is the occurrence of seizures. Determining the underlying etiology for neonatal seizures is critical. Etiology determines prognosis and outcome and guides therapeutic strategies.^[1] (See Etiology, Prognosis, Treatment, and Medication.)

The neonatal period is limited to the first 28 days of life in a term infant. For premature infants, this term usually is applied until gestational age 44 weeks; ie, the age of the infant from conception to 44 weeks (ie, 4 wk after term).

Seizure characteristics

Most neonatal seizures occur over only a few days, and fewer than half of affected infants develop seizures later in life. Such neonatal seizures can be considered acute reactive (acute symptomatic), and therefore the term neonatal epilepsy is not used to describe neonatal seizures.^[2]

Seizures in neonates are relatively common, with variable clinical manifestations. Their presence is often the first sign of neurologic dysfunction, and they are powerful predictors of long-term cognitive and developmental impairment. (See Prognosis.)

Most seizures in the neonate are focal, although generalized seizures have been described in rare instances.

Subtle seizures are more common in full-term than in premature infants. Video electroencephalogram (EEG) studies have demonstrated that most subtle seizures are not associated with electrographic seizures. Examples of subtle seizures include chewing, pedaling, or ocular movements.^[3]

Neonatal seizure classification

Clonic seizures

These movements most commonly are associated with electrographic seizures. They often involve 1 extremity or 1 side of the body. The rhythm of the clonic movements is usually slow, at 1-3 movements per second.

Tonic seizures

These may involve 1 extremity or the whole body. Focal tonic seizures involving 1 extremity often are associated with electrographic seizures.

Generalized tonic seizures often manifest with tonic extension of the upper and lower limbs and also may involve the axial musculature in an opisthotonic fashion. Generalized tonic seizures mimic decorticate posturing; the majority are not associated with electrographic seizures.

Myoclonic seizures

These may occur focally in 1 extremity or in several body parts (in which case they are described as multifocal myoclonic seizures).

Focal and multifocal myoclonic seizures typically are not associated with electrographic correlates. Generalized myoclonic jerks are possibly the clinical equivalent of infantile spasms.

The biochemical effects of neonatal seizures include derangements of energy metabolism. Energy-dependent ion pumps are compromised, and adenosine diphosphate (ADP) levels rise. The rise in ADP stimulates glycolysis with the ultimate increase in pyruvate, which accumulates as a result of compromised mitochondrial function.

Patient education

For patient education information, see the Brain and Nervous System Center, as well as Seizures in Children and Seizures Emergencies.

Seizures occur when a large group of neurons undergo excessive, synchronized depolarization. Depolarization can result from excessive excitatory amino acid release (eg, glutamate) or deficient inhibitory neurotransmitter (eg, gamma amino butyric acid [GABA]).

Hypoxic-ischemic encephalopathy

Another potential cause is disruption of adenosine triphosphate (ATP) ̶ dependent resting membrane potentials, which cause sodium to flow into the neuron and potassium to flow out of the neuron. Hypoxic-ischemic encephalopathy disrupts the ATP-dependent sodium-potassium pump and appears to cause excessive depolarization. It is an important cause of neonatal seizures.^{[1, 4]}

Seizures resulting from hypoxic-ischemic encephalopathy may be seen in term and premature infants. They frequently present within the first 72 hours of life. Seizures may include subtle, clonic, or generalized seizures.

Hemorrhage

Intracranial hemorrhage occurs more frequently in premature than in term infants. Distinguishing infants with pure hypoxic-ischemic encephalopathy from those with intracranial hemorrhage often is difficult.

Subarachnoid hemorrhage is more common in term infants. This type of hemorrhage occurs frequently and is not clinically significant. Typically, infants with subarachnoid hemorrhage appear remarkably well.

Germinal matrix-intraventricular hemorrhage is seen more frequently in premature than in term infants, particularly in infants born prior to 34 weeks' gestation. Subtle seizures are seen frequently with this type of hemorrhage.

Subdural hemorrhage is seen in association with cerebral contusion. It is more common in term infants.

Metabolic disorders

Metabolic disturbances include hypoglycemia, hypocalcemia, and hypomagnesemia. Less frequent metabolic disorders, such as inborn errors of metabolism, are seen more commonly in infants who are older than 72 hours. Typically, they may be seen after the infant starts feeding.

Intracranial infections

Intracranial infections (which should be ruled out vigorously) that are important causes of neonatal seizures include meningitis, encephalitis (including herpes encephalitis), toxoplasmosis, and cytomegalovirus (CMV) infections. The common bacterial pathogens include Escherichia coli and Streptococcus pneumoniae.

Malformation syndromes

While most cerebral malformations present with seizures at a later age, major malformation syndromes are important to consider. Lissencephaly, pachygyria, polymicrogyria, and linear sebaceous nevus syndrome can present with seizures in the neonatal period.

Benign neonatal seizures

Benign neonatal seizure syndromes can be characterized by familial or idiopathic seizures. Benign familial neonatal seizures typically occur in the first 48-72 hours of life; the seizures disappear by age 2-6 months. A family history of seizures is usual. Development is typically normal in these infants.

Benign idiopathic neonatal seizures typically present at day 5 of life (ie, fifth day fits), with the vast majority presenting between days 4 and 6 of life. Seizures are often multifocal. Cerebrospinal fluid (CSF) analysis is usually unremarkable.

The incidence of neonatal seizures in the United States has not been clearly established, although an estimated frequency of 80-120 cases per 100,000 neonates per year has been suggested. The incidence of seizures is higher in the neonatal period (ie, the first 4 wk after birth) than at any other time of life.^[5]

Age-related demographics

Neonatal seizures by definition occur within the first 4 weeks of life in a full-term infant and up to 44 weeks from conception for premature infants. Seizures are most frequent during the first 10 days of life.

Prognosis is determined by etiology for neonatal seizures. If the EEG background is normal, the prognosis is excellent for seizures to resolve; normal development is likely.^{[6, 7]}

Severe EEG background abnormalities indicate poor prognosis; such patients frequently have cerebral palsy and epilepsy. The presence of spikes on EEG is associated with a 30% risk of developing future epilepsy.

The prognosis following neonatal seizures that result from isolated subarachnoid hemorrhage is excellent, with 90% of children not having residual neurologic deficits.

Scoring system

Pisani et al devised a scoring system for early prognostic assessment after neonatal seizures. Analysis of 106 newborns who had neonatal seizures and were followed prospectively to 24 months' postconceptional age identified 6 independent risk factors for adverse outcome: (1) birth weight, (2) Apgar score at 1 minute, (3) neurologic examination at seizure onset, (4) cerebral ultrasonogram, (5) efficacy of anticonvulsant therapy, and (6) presence of neonatal status epilepticus.

Each variable was scored from 0 to 3 to represent the range from normal to severely abnormal; these were then added together to produce a total composite score, ranging from 0 to 12. A cutoff score of 4 or higher provided the greatest sensitivity and specificity for prediction of adverse neurologic outcome.^[8]

Morbidity and mortality

Neonatal seizures are a risk factor that markedly increases rates of long-term morbidity and neonatal mortality. The presence of neonatal seizures is the best predictor of long-term physical and cognitive deficits. Complications of neonatal seizures may include the following:

• Cerebral palsy
• Cerebral atrophy
• Hydrocephalus ex-vacuo
• Epilepsy
• Spasticity
• Feeding difficulties