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Official reprint from UpToDate

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Clinical features, evaluation, and diagnosis of neonatal seizures

Author: Renee Shellhaas, MD, MS

Section Editors: Douglas R Nordli, Jr, MD, Joseph A GarciaPrats, MD

Deputy Editor: April F Eichler, MD, MPH

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

Literature review current through: Apr 2017. | This topic last updated: Aug 22, 2016.

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 etiologyspecific 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 [24] and may be even higher in premature infants [5]. Seizure incidence varies with

some specific risk factors. Occurrence increases with decreasing gestational age and birth weight, and with

increasing acuity of illness [2,6,7].

ETIOLOGY — Almost all neonatal seizures are "symptomatic" seizures, occurring as a consequence of a

specific identifiable etiology (table 1 and table 2) [812]. Most etiologies can be broadly categorized as:

In wellappearing 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 agedependent properties of the immature brain that enhance seizure

initiation, maintenance of the seizure discharge, and propagation of the seizure discharge [13]. The clinical

events that are most consistently due to neonatal seizures are focalclonic, focaltonic, some types of

myoclonic, and epileptic spasms. Nonseizure 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 [1421]. These mainly classify

seizures according to their motor manifestations (focal clonic, multifocal clonic, generalized tonic, myoclonic,

®

®

Neonatal encephalopathy and hypoxicischemic encephalopathy

Structural brain injuries, including ischemic and hemorrhagic stroke

Metabolic disturbances (most often glucose and electrolyte abnormalities)

CNS or systemic infections



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).

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 — Focalclonic 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 EEG seizure activity, with each contraction

having a consistent, timelocked relationship to EEG seizure discharges.

Compared with nonseizure movements such as clonus or tremor, the jerking movements of a focalclonic

seizure are consistently slower and more rhythmic. Focalclonic 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 focalclonic seizures may be the most easily recognized by observers, these events do have features

that may be unique to the neonatal period. Focalclonic 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.

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 welldefined 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 neuromuscularjunction. In addition, some myoclonic seizures may be provoked by stimulation and suppressed by limbrestraint or body repositioning.

Epileptic spasms — Epileptic spasms may occur in neonates, although they are rare. Spasms primarilyinvolve truncal muscles and limbs. They are flexor, extensor, or mixed flexorextensor. The clinicalappearance of the events may be affected by the body position of the neonate at the time of the seizure. Thespasm begins with an initial muscle contraction that is transiently maintained, followed by relaxation of themuscle.

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

Autonomic signs — Clinical changes related to the autonomic nervous system have been reported to bemanifestations of neonatal seizures. These changes include: alterations in heart rate, respiration and bloodpressure, flushing, salivation, and pupil dilatation [19,22,23]. However, the occurrence of any of these findingsin isolation as true electrographic seizures is rare. When they do occur, they do so most consistently inassociation with other clinical motor manifestations of seizures [16]. (See 'Abrupt changes in vital signs'below.)

Subclinical seizures — Most neonatal seizures have no overt clinical manifestations [2427]. A preverbalinfant cannot communicate sensory phenomena associated with seizures (eg, a visual change associatedwith an occipital seizure or a sense of déjà vu due to a temporal lobe seizure), and unless the seizureoriginates in, or migrates to, the motor cortex, there will generally not be a clear abnormal movement. In asinglecenter review of 400 continuous video EEG studies performed in critically ill neonates, electrographicseizures were captured in 26 percent of monitored patients, and 24 percent of seizures had no clinicalcorrelate [28]. Others have reported much higher rates of subclinical seizures [2427].

DIFFERENTIAL DIAGNOSIS — Seizures in the neonate can be difficult to distinguish from abnormal, nonseizure paroxysmal events or normal newborn behaviors, and EEG is often required to distinguish amongthem. As demonstrated by the following studies, bedside clinical observation is inadequate for accurateneonatal seizure diagnosis [16,29,30]:

Inaccurate neonatal seizure diagnosis has important consequences. Neonates with subclinical seizures areundertreated without EEG screening, while those whose paroxysmal events are not seizures may be exposedto unnecessary medications. (See 'Diagnosis' below.)

Nonseizure 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

In one study, neonatal intensive care unit (NICU) nurses and physicians were trained to record everysuspected seizure event for a sample of highrisk neonates who were undergoing conventional EEGrecording. Just 9 percent (48 of 526) of all EEGconfirmed seizures had clinical manifestations that werenoted in the bedside logs, while 78 percent (129 of 177) of the abnormal paroxysmal events documentedby NICU clinicians had no EEG correlate (ie, the documented events were not seizures) [29].

In another study, 137 nurses and doctors reviewed video recordings of electroclinical seizures (EEGconfirmed seizures that had definite clinical manifestations) and nonseizure events (clinicallyapparentevents that had no corresponding EEG change) [30]. Interobserver agreement was poor (multiraterkappa 0.210.29), and although twothirds of clonic seizures were correctly diagnosed, only one third ofseizures with other semiologies were accurately identified. Importantly, less than half of nonseizureevents (eg, nonseizure clonus, benign sleep myoclonus, and other nonspecific movements) wereclassified correctly.



while they are experiencing electroclinical seizures, such as focalclonic or focaltonic 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 [1,16]. 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 nonseizure neonatal events include various motor automatisms (table 4) and tonic posturing.

Like epileptic seizures, nonseizure paroxysmal events in the neonate are often symptomatic of underlying

nervous system pathology and should be evaluated just as systematically as epileptic seizures.

Both tonic posturing and motor automatisms are considered to be of nonepileptic origin. 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" [1,16].

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 focalclonic 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 nonseizure paroxysmal events from electroclinical seizures [29,30]. (See "Nonepileptic

paroxysmal disorders in infancy".)

Normal newborn behaviors — Neonatal seizures must be differentiated from normal, nonseizure behaviors

of the newborn. Some normal behaviors of preterm and fullterm 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 nonREM sleep and has been

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 oralbuccallingual 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,

swimminglike 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.



referred to as benign neonatal myoclonus [31]. 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 [25,32]. 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 [33]. 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 atrisk infants undergo EEG monitoring, high rates of both false positive and false

negative clinical diagnoses are demonstrated (27 and 81 percent, respectively) [29,30].

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 [34]. Seizures may or may not have a clinical manifestation.

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 multichannel video EEG

monitoring [35]. Since this testing is specialized and resourceintensive, it should be reserved for newborns at

highest risk for seizures. There are many examples of highrisk clinical scenarios, but in general EEG

monitoring should be considered for newborns with proven or suspected acute brain injury and comorbid

encephalopathy.

A routinelength, 60minute 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 [35]. 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 [12].

An “electroclinical seizure” occurs when the clinical event overlaps in time with an EEGconfirmed

seizure.

A “subclinical seizure” is an EEGconfirmed seizure without associated clinical signs.

Clinical events that have no EEG correlate are not seizures.



If the interictal background is stable and no seizures are recorded after 24 hours, then monitoring may bediscontinued. An exception is often made for neonates treated with therapeutic hypothermia for hypoxicischemic encephalopathy (HIE). These infants are frequently monitored throughout cooling and rewarmingdue to the high incidence of seizures in this patient population (about 50 percent will have neonatal seizures)[35,36].

If seizures are identified, EEG monitoring should continue until the infant is seizurefree for 24 hours, unlessthis duration of monitoring is not in the infant’s best interests (eg, a newborn with seizures due to a severebrain malformation might not be expected to gain complete seizure control). Similarly, the guidelines specifythat transfer to a different intensive care facility, solely for the purposes of EEG monitoring, might not alwaysbe in the infant’s best interest and should be considered on a casebycase basis [35].

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 beseizures, then monitoring for that purpose may be discontinued.

Serial routinelength EEGs — When videoEEG monitoring is unavailable, routinelength EEG recordingwith simultaneous observation by clinicians or EEG technologists trained in the recognition andcharacterization of neonatal seizures remains the standard of care and can provide clinically importantinformation.

Reducedmontage EEG — Another option is the limitedchannel digital bedside EEG, which combinesamplitudeintegrated EEG (aEEG) with 1 or 2channel EEG. aEEG should not be considered equivalent toconventional multichannel video EEG, but it can be a useful adjuvant tool when videoEEG is not available[36].

While this technique is increasingly used in both term and preterm infants, there are important limitations[37,38]. Not all electrographic seizures are detected by this modality because of limited coverage of the scalp[39], low amplitudes, and slow frequency of typical seizures [40]. In addition, artifact in these unattendedrecordings with no simultaneous video recording can cause falsepositive interpretations. The reportedsensitivity and specificity varies between 25 and 80 percent, in part depending upon the experience of thereader [40,41] and the use of 1 versus 2channel aEEG and the associated raw EEG tracings [4245].

Despite these limitations, when standard EEG or continuous standard EEG recordings are not readilyavailable, aEEG can be a useful tool; one study found that the use of aEEG improved clinical decision makingand resulted in fewer neonates treated for seizures based solely on clinical findings [46].

The development of automated seizure detection systems holds promise for better and more widely availableEEG monitoring in the future, but current systems are not currently sufficiently reliable [38].

ETIOLOGIC EVALUATION — If a diagnosis of neonatal seizures is being entertained, an expeditedevaluation for the etiology is warranted. Most neonatal seizures are symptomatic manifestations of acutebrain injury and many require urgent, specific treatment. Therefore, the evaluation for an underlying etiologyshould 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 suchas nuchal cord or cord thrombosis, fetal heart rate decelerations, meconium, low Apgar scores, andplacental abnormalities. The nature of the delivery is also important, as infants born by operative vaginaldelivery are more likely to have intracranial hemorrhage. Other risk factors for birth injury includemacrosomia, 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



Physical examination — Aspects of the physical examination may direct further testing and provide clues tothe underlying etiology (table 5). The general examination should evaluate vital signs and assess forbirthmarks, somatic abnormalities or facial dysmorphisms, and any potential sign of infection (eg, bulgingfontanelle to suggest meningitis, or rash to suggest TORCH infection).

The neurologic examination should include measurement of head circumference, assessment of mentalstatus and level of alertness, cranial nerve exam, and motor exam to detect asymmetry in spontaneousmovements 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, andrespiratory distress after an initial symptomfree period of several days. Some infants may present withisolated seizures, however. Seizure characteristics that may suggest an underlying metabolic defect includemyoclonic seizure semiology and seizures that are refractory to conventional treatment. (See "Etiology andprognosis of neonatal seizures", section on 'Inborn errors of metabolism'.)

Laboratories — Suggested laboratory tests are presented in the table (table 6). Signs and symptoms ofsystemic and central nervous system (CNS) infection can be subtle and nonspecific in newborns. If infectionis suspected, appropriate cultures should be drawn and treatment initiated, including antibiotics at meningealdoses 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 consideredwhenever there is clinical suspicion for sepsis, since clinical signs of CNS infection can be lacking in younginfants 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 seizureswithout a clear etiology on initial evaluation and structural imaging. In that instance, the lumbar puncture isperformed to assess for metabolic disorders.

Neuroimaging — MRI is the preferred imaging modality and should be performed in all neonates withseizures to evaluate for the presence of intracranial hemorrhage, ischemic stroke, brain malformations, andevidence of hypoxic ischemic damage. In addition to routine sequences, MR angiography should be obtainedif arterial ischemic stroke or vascular malformation are suspected. MR venography is indicated to evaluate forvenous sinus thrombosis; this is particularly important in full term infants. MR spectroscopy can be performedwhere 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 singlecenter prospective study of 77 infants with neonatal seizures, MRI was abnormal in 45 out of 70infants imaged (64 percent). The most common findings were white matter abnormalities (19 percent), focalcortical abnormalities (14 percent), abnormal deep gray nuclei (13 percent), and multifocal or diffuse corticalabnormalities (11 percent) [47]. Isolated subdural or extradural hemorrhage was present in five cases. In ninecases, 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, cranialultrasound 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 hashigh sensitivity and specificity for locating hemorrhages and defining ventricular size. (See "Clinical features,diagnosis, and treatment of neonatal encephalopathy", section on 'Cranial sonography'.)

diseases or other infections (neonatal transmission of 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 unknowncauses or consanguinity (inborn errors of metabolism) and family history of epilepsy, particularly neonatal(benign familial neonatal epilepsy).



Computed tomography (CT) should generally be avoided in young children, especially neonates, since MRIprovides superior resolution and does not involve exposure to ionizing radiation [35,36].

SUMMARY AND RECOMMENDATIONS

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Topic 6152 Version 16.0

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 treatableetiology and should prompt an immediate evaluation to determine cause and to institute etiologyspecifictherapy. (See 'Etiology' above.)

Seizures in the neonate have unique clinical features when compared with those of older infants andchildren. The most common clinical seizure types in neonates are focalclonic, focaltonic, some types ofmyoclonic, and epileptic spasms (table 3), but most neonatal seizures are subclinical. (See 'Clinicalfeatures' above.)

Eletrographiconly (ie, subclinical) seizures occur without clinical manifestations and are very common inthe neonate. These seizures have similar pathogenesis and prognostic implications as electroclinicalseizures. (See 'Subclinical seizures' above.)

Neonatal seizures must be differentiated from nonepileptic paroxysmal events and nonseizure behaviorsof the newborn, and EEG is often required to distinguish among them. Bedside clinical observation isinadequate for accurate neonatal seizure diagnosis. (See 'Differential diagnosis' above and "Nonepilepticparoxysmal 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 clinicalcharacterization of the events, determination of whether the episodes are seizures or nonseizure events,and identification of an underlying etiology. (See 'Diagnosis' above and 'Etiologic evaluation' above.)

VideoEEG is the gold standard for diagnosis and quantification of seizures in neonates. EEG monitoringshould be targeted at newborns with proven or suspected brain injury and comorbid encephalopathy.When EEG monitoring is not available, serial routinelength EEGs or continuous amplitudeintegratedEEGs may be used as adjuvant diagnostic tools. (See 'Video EEG monitoring' above.)



GRAPHICS

Common etiologies of neonatal seizures

Hypoxicischemic encephalopathy

Ischemic stroke

Arterial

Venous

Intracranial hemorrhage

Intraparenchymal

Intraventricular

Subarachnoid

Subdural

Neonatalonset epilepsy

Epileptic encephalopathy/genetic epilepsy syndrome

Congenital brain malformation

Benign familial neonatal epilepsy

Central nervous system infection

Meningitis

Encephalitis

Intrauterine (prenatal) infection

Metabolic disturbance

Hypoglycemia

Hypocalcemia

Hypomagnesemia

Inborn error of metabolism

http://www.lww.com

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Etiologies of neonatal seizures

Acute

Acute neonatal encephalopathy (includes classichypoxicischemic encephalopathy, both ante andintrapartum)

Arterial ischemic stroke

Sinovenous thrombosis

Extracorporeal membrane oxygenation

Congenital heart disease

Vein of Galen malformation

Giant arteriovenous malformation

Hypertensive encephalopathy

Intracranial hemorrhage (subdural subarachnoid,intraventricular, intraparenchymal)

Trauma (intrapartum and nonaccidental)

Infections (sepsis, meningitis, encephalitis)

Transient, simple metabolic disorders

Inborn errors of metabolism (including pyridoxinedependent seizures)

Intoxication

Chronic

Isolated cerebral dysgenesis, eg, lissencephaly,hemimegalencephaly

Cerebral dysgenesis associated with inborn errors ofmetabolism

Chronic infection (TORCH [toxoplasmosis, otherinfections, rubella, cytomegalovirus, and herpessimplex] syndromes)

Neurocutaneous syndromes

Incontinentia pigmenti (Bloch Sulzberger syndrome)

Hypomelanosis of Ito

SturgeWeber syndrome

Tuberous sclerosis

Linear sebaceous nevus (epidermal nevus syndrome)

Genetic conditions

22Q11 microdeletion

ARX (Aristalessrelated homeobox) mutations

Specific very early onset epilepsy syndromes

Fifthday fits (benign neonatal convulsions)

Benign familial neonatal seizures

Early myoclonic encephalopathy

Early infantile epileptic encephalopathy

Migrating partial seizures of infancy

Reproduced with permission from: Chapman KE, Mizrahi EM, Clancy RR. Neonatal seizures. In: Wyllie's Treatment ofEpilepsy: Principles and Practice, 5th Edition, Lippincott Williams & Wilkins, Philadelphia 2010. Copyright © 2010Lippincott Williams & Wilkins. www.lww.com.




Clinical characteristics, classification, and presumed pathophysiology of neonatalseizures

Focal clonic

Repetitive, rhythmic contracts of muscle groups of the limbs, face or trunk

May be unifocal or multifocal

May occur synchronously or asynchronously in muscle groups on one side of the body

May occur simultaneously, but asynchronously on both sides

Cannot be suppressed by restraint

Pathophysiology: epileptic

Focal tonic

Sustained posturing of single limbs

Sustained asymmetrical posturing of the trunk

Sustained eye deviation

Cannot be provoked by stimulation or suppressed by restraint

Pathophysiology: epileptic

Generalized tonic

Sustained symmetrical posturing of limbs, trunk and neck

May be flexor, extensor or mixed extensor/flexor

May be provoked or intensified by stimulation

May be suppressed by restraint or repositioning

Presumed pathophysiology:nonepileptic

Myoclonic

Random, single, rapid contractions of muscle groups of the limbs, face or trunk

Typically not repetitive or may recur at a slow rate

May be generalized, focal or fragmentary

May be provoked by stimulation

Presumed pathophysiology:may be epileptic or nonepileptic

Spasms

May be flexor, extensor, or mixed extensor/flexor

May occur in clusters

Cannot be provoked by stimulation or suppressed by restraint

Pathophysiology: Epileptic

Motor Automatisms

Described in table "Motor automatisms"

Adapted with permission from: Mizrahi, EM, Kellaway, P. Diagnosis and Management of Neonatal Seizures. LippincottRaven, Philadelphia 1998. p.181. Copyright © 1998 Lippincott Williams & Wilkins.




Motor automatisms in Neonatal seizures

Ocular signs

Random and roving eye movements or nystagmus (distinct from tonic eye deviation)

May be provoked or intensified by tactile stimulation

Presumed pathophysiology: nonepileptic

Oralbuccallingual movements

Sucking, chewing, tongue protrusions



Progression movements

Rowing or swimming movements

Pedaling or bicycling movements of the legs


May be suppressed by restraint or repositioning


Complex purposeless movements

Sudden arousal with transient increased random activity of limbs



Adapted with permission from: Mizrahi, EM, Kellaway, P. Diagnosis and Management of Neonatal Seizures. LippincottRaven, Philadelphia 1998. p.181. Copyright © 1998 Lippincott Williams & Wilkins.




Key general physical examination findings for newborns with suspected seizures

Physicalexamination

Diagnostic considerations based on findings

Head circumference Macrocephaly Hydrocephalus or hemimegalencephalyMicrocephaly Congenital CNS infections (especially TORCH infections) orcongenital CNS lesions

Skin examination Vesicular lesions Consider HSV infectionVesicular lesions in a dermatomal pattern Incontinentia pigmenti

Port wine stain of the forehead/eyelid Consider SturgeWeber syndrome andevaluate for glaucomaNevus or discoloration in a dermatomal or whorled pattern Developmentalcerebral dysgenesis"Blueberry muffin" skin appearance Congenital Rubella infection (or other TORCHinfections)Ash leaf macule Tuberous sclerosisCutis aplasia (lack of hair and skin in a localized area) Associated developmentalcerebral dysgenesis

Ophthalmologicalexamination

Hypoplastic optic nerves Cerebral dysgenesis (eg, septooptic dysplasia)Chorioretinitis Congenital CNS infections

Abnormal retinal pigmentation Neuronal ceroid lipofuscinosisColoboma Agenesis of the corpus callosumCongenital cataract Congenital CNS infections (especially TORCH infections) ormetabolic (storage) diseases

Facial (or other)dysmorphism

Hypotelorism, cleft lip/palate (midface abnormalities) Cerebral dysgenesis (eg,holoprosencephaly)Multiple congenital anomalies Chromosomal abnormalities (trisomy syndromes,partial deletions/duplications)

Mental status Irritable, jittery Neonatal encephalopathy (eg, due to HIE, neonatal abstinencesyndrome)Lethargy, decreased responsiveness Neonatal encephalopathy (eg, due to HIE);severe systemic illness and/or infection (eg, meningoencephalitis)

CNS: central nervous system; HIE: hypoxicischemic encephalopathy; HSV: herpes simplex virus; TORCH: toxoplasmosis,rubella, cytomegalovirus, herpes simplex virus.




Evaluation of a neonate with seizures

Evaluation Firsttier tests Secondtier tests

Clinical Complete history, general physical andneurologic exams

Dilated ophthalmologic exam

Pyridoxine/PLP therapeutic trials*

Blood Sodium, glucose, calcium, magnesium, liverfunction tests, ammonia, lactate, pyruvate,amino acids

Arterial blood gas, pH, lactate, pyruvate

Newborn screen

TORCH titers (toxoplasmosis, otherinfections, rubella, cytomegalovirus, herpessimplex)

Carnitine, acylcarnitine, carbohydratedeficient transferrin

Biotinidase enzyme activity

Urine Urine culture

Toxicology screen

Reducing substances, sulfites, organic acids,guanidinoacetate, creatine, alphaAASA

Cerebrospinal fluid Cell counts and differential

Glucose and total protein

HSV1/2 PCR

Gram stain and culture

Lactate

Amino acids

Neurotransmitter profile

Neuroimaging MRI with MR angiography and venography

Cranial ultrasound

MR spectroscopy

alphaAASA: alphaaminoadipic semialdehyde; HSV: herpes simplex virus; MRI: magnetic resonance imaging;

PCR: polymerase chain reaction; PLP: pyridoxal phosphate.

* Consider in cases of refractory neonatal seizures unresponsive to conventional antiepileptic drugs. ¶ If biotinidase deficiency is not included in newborn screen. Δ Composition of the newborn screening panel varies by state and country. § If available and MRI cannot be obtained in a timely manner.


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Official reprint from UpToDate ©2017 UpToDate · Section Editors:Douglas R Nordli, Jr, MD, Joseph A GarciaPrats, MD Deputy Editor:April F Eichler, MD, MPH All topics are updated