Neonatal Seizures

Neonatal Seizures

Arnold J. Sansevere

Ann M. Bergin

I. INTRODUCTION. Seizures occur more frequently in the neonatal period than at any other time of life. Estimates of the incidence of neonatal seizures vary according to case definition, method of ascertainment and definition of the neonatal period, and range from 1 to 5/1,000 live births. In neonates, the vast majority of seizures are symptomatic of underlying disorders, although primary epileptic disorders may also present in this age group. The occurrence of seizure may be the first clinical indication of neurologic disorder.

Developmental immaturity influences many aspects of diagnosis, management, and prognosis of seizures in the newborn: (i) Clinical seizure patterns in the neonate reflect the “reduced connectivity” in the neonatal brain, with prominence of focal ictal characteristics and rarity of generalized patterns of clinical seizures. (ii) The balance of excitatory and inhibitory processes in the immature brain are weighted toward excitation with an excess of glutamatergic synapses over inhibitory (usually gamma-aminobutyric acid [GABA]-ergic) synapses. In fact, in some regions of the neonatal brain, GABA may temporarily act as an excitatory neurotransmitter via an alteration in chloride gradient and transportation in the immature brain. These developmental features may underlie the neonate’s tendency to frequently recurrent seizures and may explain the poor efficacy of traditionally used GABA-ergic antiepileptic agents (phenobarbital, benzodiazepines). (iii) Systemic processes are also immature, leading to altered drug handling compared to older children. (iv) The immature brain may be more susceptible to developmental effects of anticonvulsant medications.

II. DIAGNOSIS. An epileptic seizure is a change in neurologic function (motor, sensory, experiential, or autonomic) that is associated with an abnormal synchronous discharge of cortical neurons. This abnormal electrical discharge may be recorded by electroencephalogram (EEG). At all ages, including in the newborn, paroxysmal behaviors may occur, which raise suspicion of electrical seizure but which lack correlating patterns on scalp EEG. Management of these events is difficult at any age and controversial in the newborn. For this review, only those paroxysmal events associated with an electrographic seizure pattern are considered.

Early diagnosis of neonatal seizures is important to allow (i) identification and treatment of underlying disorders, (ii) treatment to prevent additional seizures and seizure-related systemic effects such as hypoxemia and hypertension, (iii) treatment of seizures to possibly prevent seizure-related excitotoxic neuronal injury. Diagnosis of seizures in the neonate requires knowledge of the clinical patterns associated with electrographic seizures at this age and confirmation with EEG, ideally accompanied by video telemetry. The EEG usually demonstrates a rhythmic focal correlate associated with, but typically of longer duration than, the clinical event. A focus of origin and spread to adjacent areas can be seen (Fig. 56.1). The more severely encephalopathic the infant, the less the seizure pattern tends to evolve in waveform and topographic spread.

Nonepileptic paroxysmal events are common in the encephalopathic infant, and unlike seizures, lack an EEG seizure pattern. Nonepileptic events are often stimulus-evoked and may be altered or stopped by gentle restraint and/or change in position (Table 56.1).

In addition, video-EEG recordings have revealed that up to 80% of electrographic seizures in neonates lack a clinical correlate. This is particularly likely in encephalopathic newborns. This phenomenon is described as electroclinical dissociation or uncoupling. Whether subclinical electrographic seizures cause additional brain injury in the newborn is unproven to date. Recent studies have suggested that higher degrees of seizure burden and neonatal status epilepticus may impact neurologic outcome as well as mortality.

A. Common clinical seizure patterns

1. Focal clonic seizures. This pattern may occur unilaterally, sequentially in different limbs, or simultaneously but asynchronously. The movement is rhythmic, biphasic with a fast contraction phase, and a slower relaxation. A clinical correlate may be present for only a small portion of the total duration of the electrographic seizure. Face, upper or lower limbs, eyes, or trunk may be involved.

2. Focal tonic seizures. Patterns include a sustained posture of a single limb, tonic horizontal eye deviation, or asymmetric tonic truncal postures. In contrast to focal tonic events, generalized tonic movements are generally not accompanied by seizure patterns on EEG.

3. Myoclonic seizures. These are characterized by a rapid movement usually of flexion. Of the varieties of myoclonus occurring in the newborn, generalized myoclonus usually involving both upper limbs and less commonly the lower limbs, is most often associated with an EEG seizure pattern. Focal or multifocal myoclonic events are usually not associated with such patterns.

Figure 56.1. Left parasagittal neonatal seizure with focal clonic seizure. Electrographic seizure begins in the left parasagittal area (open arrow), and 12 seconds later, focal clonus of the right foot is noted.

Table 56.1. Differential Diagnosis of Neonatal Seizure

Paroxysmal Nonepileptic Event


Clinical Features

Differentiating Features

Benign neonatal sleep myoclonus

Most common entity misdiagnosed as seizure in the neonate

Neonate is term, healthy, and thriving.

May be present from birth to 3 months

Multifocal jerks seen in transition to and during sleep

Only present during sleep

Upon wakening, the jerking ceases

Jitteriness (tremors)

May have exposure to maternal substance abuse or use of medications, metabolic disorder, hypoglycemia, perinatal insult

Stimulus sensitive, high frequency, low amplitude, and oscillatory (not jerking movement)

Activated/exacerbated by arousal

Extinguishes or decreases with flexion of the extremity and gentle restraint

No associated abnormal eye movements or autonomic change

Apnea of prematurity

Neonate is preterm.

Apnea and bradycardia

Apnea associated with tachycardia suggests seizure.

Assess for other associated features (i.e., automatisms, oculomotor events, motor movements, etc.).

4. Autonomic seizures. Autonomic events such as apnea, often with associated tachycardia rather than bradycardia (particularly in term newborns), and/or pupillary dilatation. These are often also associated with hypertension.

Many newborns may have more than one seizure type. In premature infants, a wider range of clinical behaviors can be associated with electrographic seizure patterns, for instance, self-limited short periods of otherwise unexplained tachypnea, tachycardia, and other autonomic changes may represent seizures in the preterm infant, as may chewing, sucking, and cycling movements, which usually are not associated with EEG seizures in the term infant.

B. EEG diagnosis. Continuous electroencephalogram (cEEG), defined as >3 hours of monitoring, is considered the gold standard for the diagnosis of neonatal seizures. cEEG is particularly important given the high proportion of neonatal seizures that are subclinical (studies suggest up to 80% of neonatal seizures are electrographic only) and would go undetected without continuous monitoring due to electroclinical uncoupling or dissociation.

Including video analysis can be very helpful to correctly characterize events, preventing treatment of clinically suspicious but nonepileptic events, and avoiding misinterpretation of artifactual EEG patterns, which can be seen with suctioning, ventilation events, and physical therapy/patting.

Many neonatal intensive care units (NICUs) rely on both routine EEG and amplitude-integrated electroencephalogram (aiEEG) to evaluate cerebral function in neonates.

1. Routine neonatal EEG recording, typically of 1 hour duration, allows assessment of background activity, including cycling state change, developmental maturity, and sometimes, epileptic potential. Such recordings may identify patients at high risk for seizure, and especially if performed serially, are useful for prognostication. However, a typical clinical event is unlikely to be captured in such a short time. Where possible, 24-hour continuous recording is preferred.

2. aiEEG is a bedside technique increasingly being used by neonatologists for neuromonitoring. The background EEG activity from a limited number of electrodes (usually one to two channels, two to four electrodes) is amplified, filtered, rectified, compressed (6 cm/hour), and displayed on a semilogarithmic scale. One minute of EEG is thus represented by 1 mm of aiEEG. Electrodes are typically placed in watershed zones in the central and temporal regions. This technique allows the neonatologist to continually assess the background EEG characteristics and thereby judge the severity of encephalopathy, the improvement or deterioration over time, and response to therapies. Seizures occurring during recording of this compressed data may alter the tracing in a recognizable manner provided the seizures occur in the region of the electrodes being used for recording and are of sufficient duration. The presence of seizures may be confirmed with immediate review of raw EEG from the available one to two channels and should then be further assessed with standard EEG recording (Fig. 56.2). The sensitivity and specificity varies with the experience of the user.

III. ETIOLOGY. Once the presence of electrographic seizure has been identified, underlying etiologies, particularly reversible causes, must be sought. The details of the pregnancy (from point of conception to time of delivery), birth history, maternal history, and family history are most important in directing the initial evaluation. For instance, a history of traumatic delivery, with good Apgar scores in a term infant, raises the possibility of intracranial hemorrhage. The age at onset of seizure relative to the time of birth is also extremely important and may suggest likely etiologies. Hypoxic-ischemic encephalopathy (HIE), which is the single most common cause of neonatal seizures, usually causes seizures within the first 24 hours of life. Focal seizures in the setting of a well-appearing nonencephalopathic newborn raises suspicion for perinatal infarction. When seizures
present after the first 48 hours of life, and particularly after a period of initial well-being, infection and biochemical disorders should be considered. Seizures occurring later (e.g., >10 days of life) are more likely to be related to disorders of calcium metabolism (now rare in the United States), cortical malformation, or neonatal epilepsy syndromes, which may be benign (e.g., benign familial neonatal seizures) or severe (e.g., early infantile epileptic encephalopathy).
Multiple possible etiologies (Table 56.2) may be identified in a neonate with seizures, such as HIE with hypoglycemia, hypocalcemia, and/or intracranial hemorrhage, and each must be treated appropriately.

Figure 56.2. Amplitude integrated EEG.

Upper panel: Compressed EEG data with wide band of activity, occasionally with sudden elevation of lower margin—a marker for possible seizure.

Middle panel: Raw EEG at the timepoint indicated by the cursor in the upper panel. Single channel EEG with rhythmicity concerning for possible seizure. Full EEG required for confirmation.

Lower panel: Indication of electrode impedance, which is appropriately low. Patterns seen in the compressed EEG data are uninterpretable in the presence of high electrode impedance.

Table 56.2. Etiologies of Neonatal Seizures

Hypoxic-ischemic injury

Perinatal asphyxia

Focal infarction



Intracranial hemorrhage





CNS infection (Escherichia coli, GBS, Listeria monocytogenes, HSV)

Malformations and other structural lesions

Neuronal migration disorders

Cerebral dysgenesis

Neurocutaneous disorders, e.g., Sturge-Weber syndrome, tuberous sclerosis

Acute metabolic disorders




Inborn errors of metabolism


Organic acidurias

Peroxisomal diseases

Mitochondrial disorders

Disorder of glucose transport (GLUT-1 deficiency)

Pyridoxine-dependent seizures

Folinic acid responsive seizures

Epilepsy syndromes

Benign familial syndromes

Severe neonatal epileptic encephalopathies (EIEE, Ohtahara syndrome, EME)

CNS, central nervous system; GBS, group B Streptococcus; HSV, herpes simplex virus; GLUT-1, glucose transporter-1; EIEE, early infantile epileptic encephalopathy; EME, early myoclonic epilepsy.

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Oct 27, 2018 | Posted by in PEDIATRICS | Comments Off on Neonatal Seizures

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