Clinical features, evaluation, and diagnosis of

neonatal seizures
Author: Renée Shellhaas, MD, MS
Section Editors: Douglas R Nordli, Jr, MD, Joseph A Garcia-Prats, MD
Deputy Editor: John F Dashe, MD, PhD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.

Literature review current through: Jun 2020. | This topic last updated: Sep 19, 2018.

INTRODUCTION

The occurrence of neonatal seizures may be the first, and perhaps the only, clinical
sign of a central nervous system (CNS) disorder in the newborn infant. As such,
seizures may indicate the presence of a potentially treatable etiology and should
prompt an immediate evaluation to determine cause and to institute etiology-
specific therapy. In addition, seizures themselves may require emergent therapy,
since they may adversely affect the infant's homeostasis or they can contribute to
further brain injury.

The clinical features, evaluation, and diagnosis of neonatal seizures will be

reviewed here. The etiology and treatment of neonatal seizures and associated
epileptic syndromes are discussed separately. (See "Etiology and prognosis of
neonatal seizures" and "Neonatal epilepsy syndromes" and "Treatment of neonatal
seizures".)

EPIDEMIOLOGY

Seizures occur more often in the neonatal period than at any other time of life;
during this period, they most often occur within the first week of life [1,2]. Reported
incidence ranges from 1.5 to 5.5 per 1000 in newborns [2-4] and may be even
higher in premature infants [5,6]. Seizure incidence varies with some specific risk
factors. Occurrence increases with decreasing gestational age and birth weight,
and with increasing acuity of illness [2,7-9].

ETIOLOGY

Most neonatal seizures (approximately 85 percent) are "symptomatic" seizures,

occurring as a consequence of a specific identifiable etiology (table 1 and table 2)
[10-14]. These etiologies can be broadly categorized as:

● Neonatal encephalopathy and hypoxic-ischemic encephalopathy

● Structural brain injuries, including ischemic and hemorrhagic stroke
● Metabolic disturbances (most often glucose and electrolyte abnormalities)
● CNS or systemic infections

Epilepsy syndromes make up about 15 percent of all neonatal seizures [15]. In

well-appearing neonates with a negative work up, recurrent neonatal seizures may
be due to a genetic epilepsy syndrome such as benign familial neonatal epilepsy.
In contrast, severe neonatal epilepsy syndromes such as early (neonatal)
myoclonic encephalopathy (EME) and early infantile epileptic encephalopathy
(EIEE) are associated with an abnormal exam and a poor prognosis.

The etiology and prognosis of neonatal seizures and neonatal epilepsy syndromes
are discussed in more detail separately. (See "Etiology and prognosis of neonatal
seizures" and "Neonatal epilepsy syndromes".)

CLINICAL FEATURES

Seizures in the neonate have unique clinical features when compared with those
of older infants and children. There are age-dependent properties of the immature
brain that enhance seizure initiation, maintenance of the seizure discharge, and
propagation of the seizure discharge [16]. The clinical events that are most
consistently due to neonatal seizures are focal-clonic, focal-tonic, some types of
myoclonic, and epileptic spasms. Non-seizure paroxysmal events are common in
this age group and can sometimes be difficult to distinguish from seizures. (See
'Differential diagnosis' below.)

There have been a number of clinical classifications of neonatal seizures [17-24].

These mainly classify seizures according to their motor manifestations (focal
clonic, multifocal clonic, generalized tonic, myoclonic, and subtle). The ‘subtle’
semiology refers to seizures with signs such as abnormal eye movements, lip
smacking, swimming or pedaling movements, or apnea (table 3 and table 4).
Neonatal seizures remain distinct entities according to the International League
Against Epilepsy (ILAE) seizure classification [25].

Clinical seizure types — A typical electroclinical neonatal seizure is a sequence of

clinical events that may include different movements or behaviors that may occur
at different times within the same seizure. Importantly, neonatal seizures are not
generalized but focal (either unifocal or multifocal).

Focal clonic — Focal-clonic seizures consist of repetitive, rhythmic contractions

of specific muscle groups of the limbs, face, or trunk. Clonic movements typically
have a slow rate of repetition, particularly when larger muscle groups are involved.
They have a close relationship to the EEG seizure pattern, with each contraction
having a consistent, time-locked relationship to EEG seizure discharges.

Compared with non-seizure movements such as clonus or tremor, the jerking

movements of a focal-clonic seizure are consistently slower and more rhythmic.
Focal-clonic seizures can be differentiated from tremor or clonus by restraint of
movement. Tremor or clonus can be stopped by restraint, though clonic seizure
activity cannot, and muscle twitching can still be felt in the restrained limb.

While focal-clonic seizures may be the most easily recognized by observers, these
events do have features that may be unique to the neonatal period. Focal-clonic
seizures may be unifocal, confined to specific muscle groups including those of
the proximal or distal limbs, trunk or neck, or regions of the face. Focal seizures
may alternate between sites of involvement within the same seizure. Focal
seizures may be multifocal and may exhibit clonic activity simultaneously but
asynchronously. If all four limbs are involved, this may give the appearance of a
generalized seizure. However, more careful inspection reveals that the limbs are
not moving synchronously.

Focal seizures can migrate from one region to another. Migration may be
according to traditional Jacksonian features (ie, contiguous spread over the
cortical representation of the limbs, face and trunk) or may be more erratic in
spread. Focal seizures may also be hemiconvulsive. In this regard, a seizure may
be initially confined to the hand on one side of the body and then abruptly involve
the remainder of that side of body without an intervening Jacksonian march.

Focal tonic — Focal tonic seizures occur less often than focal clonic seizures.
Focal tonic seizures are characterized by sustained, but transient, asymmetrical
posturing of the trunk or extremities or tonic deviation of the eyes. Seizures
involving the limbs or trunk may appear as unilateral flexion of the trunk with the
body pulling down and to one side or sustained flexion or extension of a limb.
When the eyes are involved, there is sustained conjugate deviation of the eyes to
one side. Any of these events are typically associated with focal EEG seizure
activity.

Tonic seizures are the hallmark of several neonatal epilepsy syndromes (eg,
Ohtahara syndrome, KCNQ2 encephalopathy). Therefore, prominent focal tonic
semiology should trigger consideration of neonatal-onset epilepsy as the etiology.
(See "Neonatal epilepsy syndromes", section on 'Severe syndromes'.)

Myoclonic — Myoclonic seizures in neonates represent a diverse range of

movements, some epileptic in origin and some nonepileptic in origin. The
movements of myoclonic seizures are characterized by contractions of muscle
groups of well-defined regions: proximal or distal limb regions, entire limbs, trunk
or diaphragm, or face. The movements are of variable speed depending upon the
size of the muscle group involved. The movements may be isolated events or may
be repetitive; when repetitive the rate of recurrence may be slow, irregular, or
erratic.

Myoclonic events are distinguished from clonic seizures by the regular rate of
repetition and persistence of clonic events. Myoclonic seizures can be classified
as focal, generalized, or fragmentary. Focal myoclonic seizures have features
similar to focal clonic seizures except that myoclonic events are nonrepetitive and
erratic. Generalized myoclonic seizures include bilateral, symmetric jerking of all
extremities and/or muscles of the trunk and neck. Fragmentary myoclonus is
characterized by rapid, simultaneous but asynchronous, twitching of various small
muscle groups that are typically distal. Fragmentary myoclonus is typically
nonepileptic in origin.

Some forms of myoclonic seizures may occur with a consistent EEG seizure
discharge, although some do not. This reflects the fact that some myoclonic
seizures are generated at a cortical level and others are generated at more caudal
levels such as subcortical structures, brainstem, spinal cord, or neuromuscular
junction. In addition, some myoclonic seizures may be provoked by stimulation
and suppressed by limb restraint or body repositioning.

Epileptic spasms — Epileptic spasms may occur in neonates, although they are

rare. Spasms primarily involve truncal muscles and limbs. They are flexor,
extensor, or mixed flexor-extensor. The clinical appearance of the events may be
affected by the body position of the neonate at the time of the seizure. The spasm
begins with an initial muscle contraction that is transiently maintained, followed by
relaxation of the muscle.

The seizures may occur in clusters and are most often present upon arousal of the
infant from sleep. On EEG, the seizures may be associated with a generalized, high
voltage, slow wave transient or generalized voltage attenuation. Spasms are
considered electroclinical seizures and are epileptic in origin. (See "Clinical
features and diagnosis of infantile spasms".)

Autonomic signs — Clinical changes related to the autonomic nervous system

have been reported to be manifestations of neonatal seizures. These changes
include: alterations in heart rate, respiration and blood pressure, flushing,
salivation, and pupil dilatation [22,26,27]. However, the occurrence of any of these
findings in isolation as true electrographic seizures is rare. When they do occur,
they do so most consistently in association with other clinical motor
manifestations of seizures [19,28]. (See 'Abrupt changes in vital signs' below.)

Subclinical seizures — Most neonatal seizures have no overt clinical

manifestations [14,29-33]. A preverbal infant cannot communicate sensory
phenomena associated with seizures (eg, a visual change associated with an
occipital seizure or a sense of déjà vu due to a temporal lobe seizure), and unless
the seizure originates in, or migrates to, the motor cortex, there will generally not
be a clear abnormal movement. In a single-center review of 400 continuous video
EEG studies performed in critically ill neonates, electrographic seizures were
captured in 26 percent of monitored patients, and 24 percent of seizures had no
clinical correlate [34]. Others have reported much higher rates of subclinical
seizures [29-32].

DIFFERENTIAL DIAGNOSIS

Seizures in the neonate can be difficult to distinguish from abnormal, non-seizure

paroxysmal events or normal newborn behaviors, and EEG is often required to
distinguish among them. As demonstrated by the following studies, bedside
clinical observation is inadequate for accurate neonatal seizure diagnosis
[19,35,36]:
 ● In one study, neonatal intensive care unit (NICU) nurses and physicians were
trained to record every suspected seizure event for a sample of high-risk
neonates who were undergoing conventional EEG recording. Just 9 percent (48
of 526) of all EEG-confirmed seizures had clinical manifestations that were
noted in the bedside logs, while 78 percent (129 of 177) of the abnormal
paroxysmal events documented by NICU clinicians had no EEG correlate (ie,
the documented events were not seizures) [35].

● In another study, 137 nurses and doctors reviewed video recordings of

electroclinical seizures (EEG-confirmed seizures that had definite clinical
manifestations) and non-seizure events (clinically-apparent events that had no
corresponding EEG change) [36]. Interobserver agreement was poor (multi-
rater kappa 0.21-0.29), and although two-thirds of clonic seizures were
correctly diagnosed, only one third of seizures with other semiologies were
accurately identified. Importantly, less than half of non-seizure events (eg, non-
seizure clonus, benign sleep myoclonus, and other non-specific movements)
were classified correctly.

Inaccurate neonatal seizure diagnosis has important consequences. Neonates

with subclinical seizures are undertreated without EEG screening, while those
whose paroxysmal events are not seizures may be exposed to unnecessary
medications. (See 'Diagnosis' below.)

Non-seizure events — Neonatal seizures are generated by hypersynchronous

cortical neuronal discharges. They are defined by their EEG patterns and may be
electroclinical or subclinical. When infants are examined while they are
experiencing electroclinical seizures, such as focal-clonic or focal-tonic seizures,
the clinical event cannot be suppressed by restraint or repositioning of the
affected limb. In addition, between seizures, clinical events cannot be provoked by
stimulation of the infant.
In contrast, non–seizure events occur in the absence of any EEG change [1,19].
They can sometimes be provoked by stimulation of the infant, and both the
provoked and spontaneous events can typically be suppressed by restraint of the
infant or by repositioning the infant during the event. In addition, the clinical events
may increase in intensity with the increase in the repetition rate of stimulation
(temporal summation) or the sites of simultaneous stimulation (spatial
summation).

Examples of non-seizure neonatal events include various motor automatisms

(table 4) and tonic posturing. Like epileptic seizures, non-seizure paroxysmal
events in the neonate are often symptomatic of underlying nervous system
pathology and should be evaluated just as systematically as epileptic seizures.

● Motor automatisms – The term "motor automatisms" is used to characterize

clinical events referred to by some as "subtle seizures." Although these events
are sometimes electroclinical seizures, most often they are not (table 4).

Motor automatisms can often be provoked by stimulation and are considered

a manifestation of brainstem release phenomena. Unless they have associated
EEG correlates, they are not seizures. Motor automatisms may appear as oral-
buccal-lingual movements including episodic chewing, swallowing, sucking, or
repetitive tongue movements. Ocular movements appear as episodic random
or oscillatory eye movements, repetitive eye opening, episodic and
nonsustained eye deviation, or episodic dysconjugate gaze. Progression
movements resemble pedaling or bicycling movements of the legs, swimming-
like movements, rotary movement of the upper extremities, or combinations of
these movements.

● Tonic posturing – Bilateral, symmetric tonic posturing may be predominantly

flexor, extensor, or mixed. The tonic posture is sustained and may involve
bilateral limbs and the trunk. The muscle contractions are relatively long and
are of greater duration than spasms. These tonic events can be provoked by
 stimulation and suppressed by restraint or repositioning of the infant. These
events may occur in isolation, or they may occur in infants who are also
experiencing motor automatisms.

Both tonic posturing and motor automatisms are considered to be of nonepileptic

origin if they have no associated ictal rhythm on EEG. They have clinical features
that resemble exaggerated reflex behavior. They occur in infants who are
obtunded or lethargic and with EEG background characterized as depressed and
undifferentiated, features indicating the presence of forebrain depression. Tactile
stimulation of the infants may provoke posturing or motor automatisms. These
characteristics are based in reflex physiology and the events have been referred to
as "brainstem release phenomena" [1,19].

Other paroxysmal events in the neonate that can be confused with seizures
include hyperekplexia, jitteriness, tremulousness, and clonus. Such events can
occur in normal and abnormal infants and can be differentiated from other clinical
events, particularly focal-clonic seizures, by their suppression by restraint. The
clinical phenomenology of these nonepileptic paroxysmal events, especially in
relation to how they are distinguished from epileptic seizures, is discussed
separately. Importantly, clinicians have been shown to be inaccurate in
distinguishing non-seizure paroxysmal events from electroclinical seizures [35,36].
(See "Nonepileptic paroxysmal disorders in infancy".)

Normal newborn behaviors — Neonatal seizures must be differentiated from

normal, non-seizure behaviors of the newborn. Some normal behaviors of preterm
and full-term infants may raise suspicions of seizures. Normal behaviors include
stretching, nonspecific random movements that can be sudden (particularly in
preterm infants), random sucking movements, coughing, and gagging.

In addition, neonates may experience normal physiologic myoclonus during active

sleep (the precursor of rapid eye movement [REM] sleep). Myoclonus may also
occur during quiet or non-REM sleep and has been referred to as benign neonatal
myoclonus [37]. Importantly, if the neonate is otherwise healthy, the myoclonus
virtually always ceases when the infant is awoken, and it only occurs when the
neonate is asleep. This may help to distinguish this common phenomenon from
neonatal seizures. (See "Nonepileptic paroxysmal disorders in infancy", section on
'Benign neonatal sleep myoclonus'.)

Abrupt changes in vital signs — Most abrupt changes in blood pressure, heart

rate, and respirations recorded in infants in the neonatal intensive care unit (NICU)
are not manifestations of seizures [28,30]. When changes in these parameters are
manifestations of seizures, they most often occur in association with motor
phenomena or other clinical manifestations of seizures.

This was illustrated by a retrospective study of 324 continuous video EEG studies
performed for the evaluation of paroxysmal vital sign changes in children [28].
Most of the studies were performed in neonates and infants less than one year
old, and an index event was captured in 52 percent of the studies. The recorded
vital sign changes were rarely related to seizures when the change was
hypotension (0 out of 12), hypertension (1 out of 22, 4.5 percent), or bradycardia (2
out of 26, 7.7 percent), and all seizures were associated with additional clinical
signs. Vital sign changes were more likely to be ictal when the change included
oxygen desaturation (11 out of 82, 13 percent) or apnea (22 out of 83, 27 percent),
particularly when accompanied by abnormal eye movements or an abrupt
decrease in tone. Tachycardia with or without additional clinical signs was a
seizure manifestation in 2 out of 23 studies (9 percent).

DIAGNOSIS

Historically, the diagnosis of neonatal seizures was most often made based on
clinical signs. However, modern electroencephalography (EEG) studies have
demonstrated that not all clinically suspicious events are epileptic seizures (in
fact, most are not), and most neonatal seizures are subclinical.
Contemporary diagnosis of neonatal seizures therefore relies on confirmatory
electroencephalographic (EEG) characteristics. When at-risk infants undergo EEG
monitoring, high rates of both false positive and false negative clinical diagnoses
are demonstrated (27 and 81 percent, respectively) [35,36].

A neonatal seizure is defined as a definitely abnormal EEG pattern which evolves

(ie, the abnormal EEG waveform changes morphology, or the location migrates
across head regions), is of >2 microvolt (µV) amplitude, and has a duration of ≥10
seconds [38]. Seizures may or may not have a clinical manifestation.

● An "electroclinical seizure" occurs when the clinical event overlaps in time with
an EEG-confirmed seizure.
● A "subclinical seizure" is an EEG-confirmed seizure without associated clinical
signs.
● Clinical events that have no EEG correlate are not seizures.

Importantly, neonates who have high risk clinical scenarios and clinical events
which are very suspicious for seizures (eg, focal clonic jerking in a newborn with
clinical concern for acute HIE) should be evaluated and treated urgently, even if
EEG is not immediately available.

Video EEG monitoring — The gold standard for neonatal seizure diagnosis is multi-
channel video EEG monitoring [39]. Since this testing is specialized and resource-
intensive, it should be reserved for newborns at highest risk for seizures. There are
many examples of high-risk clinical scenarios, but in general EEG monitoring
should be considered for newborns with proven or suspected acute brain injury
and comorbid encephalopathy.

A routine-length, 60-minute EEG is not considered sufficient to screen for neonatal

seizures. For newborns at high risk of seizures, the American Clinical
Neurophysiology Society recommends that video EEG monitoring be recorded for
24 hours [39]. In a prospective study of 426 consecutive neonates with clinically
suspected seizures and/or electrographic seizures who underwent EEG
monitoring (82 percent with confirmed electrographic seizures), the median time
to electrographic seizure detection was seven hours from the onset of the
recording [14].

If the interictal background is stable and no seizures are recorded after 24 hours,
then monitoring may be discontinued. An exception is often made for neonates
treated with therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE).
These infants are frequently monitored throughout cooling and rewarming due to
the high incidence of seizures in this patient population (about 50 percent will
have neonatal seizures) [39,40].

If seizures are identified, EEG monitoring should continue until the infant is
seizure-free for 24 hours, unless this duration of monitoring is not in the infant’s
best interests (eg, a newborn with seizures due to a severe brain malformation
might not be expected to gain complete seizure control). Similarly, the guidelines
specify that transfer to a different intensive care facility, solely for the purposes of
EEG monitoring, might not always be in the infant’s best interest and should be
considered on a case-by-case basis [39].

If EEG monitoring is initiated in order to evaluate whether discrete, abnormal

paroxysmal events are seizures, then recording should continue until several
events are captured. If the events are determined not to be seizures, then
monitoring for that purpose may be discontinued.

Serial routine-length EEGs — When video-EEG monitoring is unavailable, routine-

length EEG recording with simultaneous observation by clinicians or EEG
technologists trained in the recognition and characterization of neonatal seizures
remains the standard of care and can provide clinically important information.

Reduced-montage EEG — Another option is the limited-channel digital bedside

EEG, which combines amplitude-integrated EEG (aEEG) with 1 or 2-channel EEG.
aEEG should not be considered equivalent to conventional multi-channel video
EEG, but it can be a useful adjuvant tool when video-EEG is not available [40].
While this technique is increasingly used in both term and preterm infants, there
are important limitations [41,42]. Not all electrographic seizures are detected by
this modality because of limited coverage of the scalp [43], low amplitudes, and
slow frequency of typical seizures [44]. In addition, artifact in these unattended
recordings with no simultaneous video recording can cause false-positive
interpretations. The reported sensitivity and specificity varies between 25 and 80
percent, in part depending upon the experience of the reader [44,45] and the use of
1 versus 2-channel aEEG and the associated raw EEG tracings [46-49].

Despite these limitations, when standard EEG or continuous standard EEG

recordings are not readily available, aEEG can be a useful tool; one study found
that the use of aEEG improved clinical decision making and resulted in fewer
neonates treated for seizures based solely on clinical findings [50].

The development of automated seizure detection systems holds promise for

better and more widely available EEG monitoring in the future, but current systems
are not currently sufficiently reliable [42,51-53].

ETIOLOGIC EVALUATION

If a diagnosis of neonatal seizures is being entertained, an expedited evaluation

for the etiology is warranted. Most neonatal seizures are symptomatic
manifestations of acute brain injury and many require urgent, specific treatment.
Therefore, the evaluation for an underlying etiology should occur in tandem with
the diagnosis and treatment of seizures.

History — The history should attempt to identify risk factors for seizures and clues
to the underlying etiology:

● Gestational and birth history – A thorough birth history should identify risk
factors for anoxic injury such as nuchal cord or cord thrombosis, fetal heart
rate decelerations, meconium, low Apgar scores, and placental abnormalities.
 The nature of the delivery is also important, as infants born by operative
vaginal delivery are more likely to have intracranial hemorrhage. Other risk
factors for birth injury include macrosomia, maternal obesity, and abnormal
fetal presentation. (See "Neonatal birth injuries", section on 'Intracranial
hemorrhage'.)

● Maternal history – Aspects of the maternal history that may be important

include previous miscarriages (congenital anomalies), gestational diabetes
(neonatal hypoglycemia), history of sexually transmitted diseases or other
infections (neonatal transmission of infection), history of illness during
pregnancy (eg, maternal rash and fever could suggest in utero viral infection),
use of prescription or illegal substances (drug intoxication or withdrawal), and
clotting or bleeding tendencies (neonatal stroke or hemorrhage).

● Family history – A detailed family history should include queries about early
sibling death from unknown causes or consanguinity (inborn errors of
metabolism) and family history of epilepsy, particularly neonatal (benign
familial neonatal epilepsy).

Physical examination — Aspects of the physical examination may direct further

testing and provide clues to the underlying etiology (table 5). The general
examination should evaluate vital signs and assess for head size, birthmarks,
somatic abnormalities or facial dysmorphisms, and any potential sign of infection
(eg, bulging fontanelle to suggest meningitis, or rash to suggest TORCH infection).

The neurologic examination should include measurement of head circumference,

assessment of mental status and level of alertness, cranial nerve exam, and motor
exam to detect asymmetry in spontaneous movements or abnormal tone that may
suggest a structural brain lesion or neonatal encephalopathy.

The typical presentation of an inborn error of metabolism usually includes poor

feeding, lethargy, and respiratory distress after an initial symptom-free period of
several days. Some infants may present with isolated seizures, however. Seizure
characteristics that may suggest an underlying metabolic defect include
myoclonic seizure semiology and seizures that are refractory to conventional
treatment. (See "Etiology and prognosis of neonatal seizures", section on 'Inborn
errors of metabolism'.)

Laboratories — Suggested laboratory tests are presented in the table (table 6).

Signs and symptoms of systemic and central nervous system (CNS) infection can
be subtle and nonspecific in newborns. If infection is suspected, appropriate
cultures should be drawn and treatment initiated, including antibiotics at
meningeal doses and acyclovir for herpes simplex virus in the appropriate clinical
scenario.

Lumbar puncture is recommended in all neonates with a positive blood culture and
should also be considered whenever there is clinical suspicion for sepsis, since
clinical signs of CNS infection can be lacking in young infants and infection is
among the most common causes of neonatal seizures. (See "Clinical features,
evaluation, and diagnosis of sepsis in term and late preterm infants", section on
'Laboratory tests'.)

If infection is not suspected, lumbar puncture is typically reserved for cases of

refractory or recurrent seizures without a clear etiology on initial evaluation and
structural imaging. In that instance, the lumbar puncture is performed to assess
for metabolic disorders.

Neuroimaging — MRI is the preferred imaging modality and should be performed

in all neonates with seizures to evaluate for the presence of intracranial
hemorrhage, ischemic stroke, brain malformations, and evidence of hypoxic
ischemic damage. In addition to routine sequences, MR angiography should be
obtained if arterial ischemic stroke or vascular malformation are suspected. MR
venography is indicated to evaluate for venous sinus thrombosis; this is
particularly important in full term infants. MR spectroscopy can be performed
where available to evaluate for certain metabolites such as glycine (nonketotic
hyperglycinemia), lactate (mitochondrial disorders), or loss of creatine (disorder of
brain creatine metabolism).

In a single-center prospective study of 77 infants with neonatal seizures, MRI was

abnormal in 45 out of 70 infants imaged (64 percent). The most common findings
were white matter abnormalities (19 percent), focal cortical abnormalities (14
percent), abnormal deep gray nuclei (13 percent), and multifocal or diffuse cortical
abnormalities (11 percent) [54]. Isolated subdural or extradural hemorrhage was
present in five cases. In nine cases, the diagnosis was made by MRI, as all other
investigations were normal or nonspecific.

If an infant is not sufficiently stable for MRI, or if there is an anticipated delay in

obtaining MRI, cranial ultrasound should be performed to evaluate for the
presence of intracranial hemorrhage or hydrocephalus. Ultrasound has the
advantage of being noninvasive and can be performed at the bedside. Ultrasound
has high sensitivity and specificity for locating hemorrhages and defining
ventricular size. (See "Clinical features, diagnosis, and treatment of neonatal
encephalopathy", section on 'Cranial ultrasound'.)

Computed tomography (CT) should generally be avoided in young children,

especially neonates, since MRI provides superior resolution and does not involve
exposure to ionizing radiation [39,40].

Genetic testing — The role of genetic testing in the clinical care of children with
epilepsy is evolving as the number of monogenetic causes of early epileptic
encephalopathy increases and specific treatments become available for some
syndromes. In a prospective cohort study of 611 consecutive newborns with
seizures, 13 percent had an epilepsy syndrome, including 35 infants (6 percent)
with epileptic encephalopathy and 32 with congenital brain malformations [15].
Among 29 neonates with epileptic encephalopathy who underwent genetic testing,
83 percent had a genetic etiology identified, most commonly KCNQ2
encephalopathy. Among 23 neonates with brain malformations, 7 had a putative
genetic etiology. (See "Neonatal epilepsy syndromes" and "Localization-related
(focal) epilepsy: Causes and clinical features", section on 'Genetic focal epilepsy
syndromes'.)

In addition to treatment implications (eg, preferential use of sodium channel

blocking antiseizure drugs in KCNQ2 encephalopathy, avoidance of these drugs in
Dravet syndrome due to SCN1A mutations), identification of a genetic etiology
assists in prognosis and genetic counseling and avoids further extensive etiologic
testing [55,56]. (See "Neonatal epilepsy syndromes", section on 'KCNQ2
encephalopathy' and "Dravet syndrome: Management and prognosis".)

Genetic testing should therefore be strongly considered in neonates with epilepsy

who do not have an acute symptomatic cause identified on initial history,
examination, and neuroimaging. When genetic testing is performed, we suggest
using a gene panel for epileptic encephalopathies and brain malformations, or
whole exome sequencing, rather than serial testing of single genes. Given the
phenotypic overlap of various genetic epilepsies, testing for multiple different
mutations at the same time is more practical and cost efficient than testing for
one mutation at a time. Specific information on genetic testing is available at
https://www.ncbi.nlm.nih.gov/gtr/. Counseling for genetic testing is discussed
separately. (See "Genetic testing".)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries

and regions around the world are provided separately. (See "Society guideline
links: Seizures and epilepsy in children".)

SUMMARY AND RECOMMENDATIONS

● Neonatal seizures may be the first, and perhaps the only, clinical sign of a
central nervous system (CNS) disorder in the newborn infant. As such,
seizures may indicate the presence of a potentially treatable etiology and
should prompt an immediate evaluation to determine cause and to institute
etiology-specific therapy. (See 'Etiology' above.)

● Seizures in the neonate have unique clinical features when compared with
those of older infants and children. The most common clinical seizure types in
neonates are focal-clonic, focal-tonic, some types of myoclonic, and epileptic
spasms (table 3), but most neonatal seizures are subclinical. (See 'Clinical
features' above.)

● Electrographic-only (ie, subclinical) seizures occur without clinical

manifestations and are very common in the neonate. These seizures have
similar pathogenesis and prognostic implications as electroclinical seizures.
(See 'Subclinical seizures' above.)

● Neonatal seizures must be differentiated from nonepileptic paroxysmal events

and non-seizure behaviors of the newborn, and EEG is often required to
distinguish among them. Bedside clinical observation is inadequate for
accurate neonatal seizure diagnosis. (See 'Differential diagnosis' above and
"Nonepileptic paroxysmal disorders in infancy".)

● The diagnosis of neonatal seizures is based upon clinical observation

combined with EEG monitoring. The diagnostic evaluation of a neonate with
suspected seizures has several objectives, including clinical characterization
of the events, determination of whether the episodes are seizures or non-
seizure events, and identification of an underlying etiology. (See 'Diagnosis'
above and 'Etiologic evaluation' above.)

● Video-EEG is the gold standard for diagnosis and quantification of seizures in

neonates. EEG monitoring should be targeted at newborns with proven or
suspected brain injury and comorbid encephalopathy. When EEG monitoring is
 not available, serial routine-length EEGs or continuous amplitude-integrated
EEGs may be used as adjuvant diagnostic tools. (See 'Video EEG monitoring'
above.)

● Genetic testing should be strongly considered in neonates with epilepsy who

do not have an acute symptomatic cause identified on initial history,
examination, and neuroimaging. When genetic testing is performed, we
suggest using a gene panel for epileptic encephalopathies and brain
malformations, or whole exome sequencing, rather than serial testing of single
genes. (See 'Genetic testing' above.)

REFERENCES

1. Kellaway P, Hrachovy RA. Status epilepticus in newborns: A perspective on ne

onatal seizures. In: Advances in Neurology, vol 34: Status Epilepticus, Delgado
-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ (Eds), Raven Press, New Y
ork 1983. p.93.

2. Lanska MJ, Lanska DJ, Baumann RJ, Kryscio RJ. A population-based study of
neonatal seizures in Fayette County, Kentucky. Neurology 1995; 45:724.

3. Ronen GM, Penney S, Andrews W. The epidemiology of clinical neonatal

seizures in Newfoundland: a population-based study. J Pediatr 1999; 134:71.

4. Saliba RM, Annegers JF, Waller DK, et al. Incidence of neonatal seizures in
Harris County, Texas, 1992-1994. Am J Epidemiol 1999; 150:763.

5. Vasudevan C, Levene M. Epidemiology and aetiology of neonatal seizures.

Semin Fetal Neonatal Med 2013; 18:185.

. Buraniqi E, Sansevere AJ, Kapur K, et al. Electrographic Seizures in Preterm

Neonates in the Neonatal Intensive Care Unit. J Child Neurol 2017; 32:880.
 7. Scher MS, Aso K, Beggarly ME, et al. Electrographic seizures in preterm and
full-term neonates: clinical correlates, associated brain lesions, and risk for
neurologic sequelae. Pediatrics 1993; 91:128.

. Glass HC, Pham TN, Danielsen B, et al. Antenatal and intrapartum risk factors
for seizures in term newborns: a population-based study, California 1998-
2002. J Pediatr 2009; 154:24.

9. Pisani F, Facini C, Bianchi E, et al. Incidence of neonatal seizures, perinatal risk

factors for epilepsy and mortality after neonatal seizures in the province of
Parma, Italy. Epilepsia 2018; 59:1764.

10. Mizrahi EM, Kellaway P. Diagnosis and Management of Neonatal Seizures, Lip
pincott-Raven, Philadelphia 1998. p.181.

11. Co JP, Elia M, Engel J Jr, et al. Proposal of an algorithm for diagnosis and
treatment of neonatal seizures in developing countries. Epilepsia 2007;
48:1158.

12. Mizrahi EM, Watanabe K. Symptomatic neonatal seizures. In: Epileptic syndro
mes in infancy, childhood and adolescence, 3rd, Roger J, Bureau M, Dravet C
H, et al (Eds), John Libbey, 2002. p.15.

13. Chapman KE, Mizrahi EM, Clancy, RR. Neonatal seizures. In: Wyllie's Treatmen
t of Epilepsy: Principles and Practice, 5th, Lippincott, Williams & Wilkens, Phila
delphia.

14. Glass HC, Shellhaas RA, Wusthoff CJ, et al. Contemporary Profile of Seizures
in Neonates: A Prospective Cohort Study. J Pediatr 2016; 174:98.

15. Shellhaas RA, Wusthoff CJ, Tsuchida TN, et al. Profile of neonatal epilepsies:
Characteristics of a prospective US cohort. Neurology 2017; 89:893.

1 . Holmes GL. Epilepsy in the developing brain: lessons from the laboratory and
clinic. Epilepsia 1997; 38:12.
17. Drefus-Brisac C, Monod N. Electroclinical studies of status epilepticus and co
nvulsions in the newborn. In: Neurological and electroencephalographic correl
ative studies in infancy, Kellaway P, Petersen I (Eds), Grune & Stanton, New Yor
k 1964. p.250.

1 . Lombroso CT. The treatment of status epilepticus. Pediatrics 1974; 53:536.

19. Mizrahi EM, Kellaway P. Characterization and classification of neonatal

seizures. Neurology 1987; 37:1837.

20. Rose AL, Lombroso CT. A study of clinical, pathological, and

electroencephalographic features in 137 full-term babies with a long-term
follow-up. Pediatrics 1970; 45:404.

21. Volpe JJ. Neonatal seizures: current concepts and revised classification.
Pediatrics 1989; 84:422.

22. Watanabe K, Hara K, Miyazaki S, et al. Electroclinical studies of seizures in the

newborn. Folia Psychiatr Neurol Jpn 1977; 31:383.

23. Volpe J. Neonatal Seizures. N Engl J Med 1973; 289:413.

24. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for
organization of seizures and epilepsies: report of the ILAE Commission on
Classification and Terminology, 2005-2009. Epilepsia 2010; 51:676.

25. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure
types by the International League Against Epilepsy: Position Paper of the ILAE
Commission for Classification and Terminology. Epilepsia 2017; 58:522.

2 . Goldberg RN, Goldman SL, Ramsay RE, Feller R. Detection of seizure activity in
the paralyzed neonate using continuous monitoring. Pediatrics 1982; 69:583.

27. Lou HC, Friis-Hansen B. Arterial blood pressure elevations during motor
activity and epileptic seizures in the newborn. Acta Paediatr Scand 1979;
 68:803.

2 . Dang LT, Shellhaas RA. Diagnostic yield of continuous video

electroencephalography for paroxysmal vital sign changes in pediatric
patients. Epilepsia 2016; 57:272.

29. Clancy RR, Legido A, Lewis D. Occult neonatal seizures. Epilepsia 1988;
29:256.

30. Clancy RR, Sharif U, Ichord R, et al. Electrographic neonatal seizures after
infant heart surgery. Epilepsia 2005; 46:84.

31. Scher MS, Alvin J, Gaus L, et al. Uncoupling of EEG-clinical neonatal seizures
after antiepileptic drug use. Pediatr Neurol 2003; 28:277.

32. Wusthoff CJ, Dlugos DJ, Gutierrez-Colina A, et al. Electrographic seizures

during therapeutic hypothermia for neonatal hypoxic-ischemic
encephalopathy. J Child Neurol 2011; 26:724.

33. Lloyd RO, O'Toole JM, Pavlidis E, et al. Electrographic Seizures during the Early
Postnatal Period in Preterm Infants. J Pediatr 2017; 187:18.

34. Wietstock SO, Bonifacio SL, Sullivan JE, et al. Continuous Video
Electroencephalographic (EEG) Monitoring for Electrographic Seizure
Diagnosis in Neonates: A Single-Center Study. J Child Neurol 2016; 31:328.

35. Murray DM, Boylan GB, Ali I, et al. Defining the gap between electrographic
seizure burden, clinical expression and staff recognition of neonatal seizures.
Arch Dis Child Fetal Neonatal Ed 2008; 93:F187.

3 . Malone A, Ryan CA, Fitzgerald A, et al. Interobserver agreement in neonatal

seizure identification. Epilepsia 2009; 50:2097.

37. Di Capua M, Fusco L, Ricci S, Vigevano F. Benign neonatal sleep myoclonus:

clinical features and video-polygraphic recordings. Mov Disord 1993; 8:191.
3 . Tsuchida TN, Wusthoff CJ, Shellhaas RA, et al. American clinical
neurophysiology society standardized EEG terminology and categorization for
the description of continuous EEG monitoring in neonates: report of the
American Clinical Neurophysiology Society critical care monitoring
committee. J Clin Neurophysiol 2013; 30:161.

39. Shellhaas RA, Chang T, Tsuchida T, et al. The American Clinical

Neurophysiology Society's Guideline on Continuous Electroencephalography
Monitoring in Neonates. J Clin Neurophysiol 2011; 28:611.

40. Glass HC, Wusthoff CJ, Shellhaas RA. Amplitude-integrated electro-

encephalography: the child neurologist's perspective. J Child Neurol 2013;
28:1342.

41. Glass HC, Kan J, Bonifacio SL, Ferriero DM. Neonatal seizures: treatment
practices among term and preterm infants. Pediatr Neurol 2012; 46:111.

42. Shah DK, Boylan GB, Rennie JM. Monitoring of seizures in the newborn. Arch
Dis Child Fetal Neonatal Ed 2012; 97:F65.

43. Glass HC, Wirrell E. Controversies in neonatal seizure management. J Child

Neurol 2009; 24:591.

44. Shellhaas RA, Soaita AI, Clancy RR. Sensitivity of amplitude-integrated

electroencephalography for neonatal seizure detection. Pediatrics 2007;
120:770.

45. Rennie JM, Chorley G, Boylan GB, et al. Non-expert use of the cerebral
function monitor for neonatal seizure detection. Arch Dis Child Fetal Neonatal
Ed 2004; 89:F37.

4 . Shah DK, Mackay MT, Lavery S, et al. Accuracy of bedside

electroencephalographic monitoring in comparison with simultaneous
 continuous conventional electroencephalography for seizure detection in term
infants. Pediatrics 2008; 121:1146.

47. Wusthoff CJ, Shellhaas RA, Clancy RR. Limitations of single-channel EEG on
the forehead for neonatal seizure detection. J Perinatol 2009; 29:237.

4 . Griesmaier E, Neubauer V, Ralser E, et al. Need for quality control for aEEG
monitoring of the preterm infant: a 2-year experience. Acta Paediatr 2011;
100:1079.

49. Ray S. Question 1. Is cerebral function monitoring as accurate as

conventional EEG in the detection of neonatal seizures? Arch Dis Child 2011;
96:314.

50. Shellhaas RA, Barks AK. Impact of amplitude-integrated

electroencephalograms on clinical care for neonates with seizures. Pediatr
Neurol 2012; 46:32.

51. Mathieson S, Rennie J, Livingstone V, et al. In-depth performance analysis of

an EEG based neonatal seizure detection algorithm. Clin Neurophysiol 2016;
127:2246.

52. Mathieson SR, Stevenson NJ, Low E, et al. Validation of an automated seizure
detection algorithm for term neonates. Clin Neurophysiol 2016; 127:156.

53. Temko A, Marnane W, Boylan G, Lightbody G. Clinical implementation of a

neonatal seizure detection algorithm. Decis Support Syst 2015; 70:86.

54. Osmond E, Billetop A, Jary S, et al. Neonatal seizures: magnetic resonance

imaging adds value in the diagnosis and prediction of neurodisability. Acta
Paediatr 2014; 103:820.

55. Scheffer IE. Genetic testing in epilepsy: what should you be doing? Epilepsy
Curr 2011; 11:107.
5 . Ottman R, Hirose S, Jain S, et al. Genetic testing in the epilepsies--report of
the ILAE Genetics Commission. Epilepsia 2010; 51:655.

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