Neonatal
Seizures
Synonyms and related keywords:
benign familial neonatal convulsions, benign neonatal
convulsions, fifth day convulsions, fifth day fits, myoclonic
seizures, newborn fits, hypoxic-ischemic encephalopathy, intracranial
hemorrhage in a newborn, subarachnoid hemorrhage in
infants, germinal matrix-intraventricular hemorrhage,
subdural hemorrhage, cerebral contusion, metabolic
disturbances, hypoglycemia, hypocalcemia, hypomagnesemia, meningitis, encephalitis, herpes
encephalitis, toxoplasmosis, cytomegalovirus, CMV infection, lissencephaly, pachygyria, polymicrogyria, linear sebaceous nevus syndrome, benign
neonatal seizure syndromes, benign idiopathic neonatal seizures, benign sleep myoclonus
Background:
The neonatal period is limited to the first 28 days of life
in a term infant. For premature infants, this term usually is applied until
gestational age 44 weeks; ie, the age of the infant
from conception to 44 weeks (ie, 4 weeks after term).
Most neonatal seizures occur over only a few days, and fewer
than half of affected infants develop seizures later in life. Such neonatal
seizures could be considered acute reactive (acute symptomatic), thus the term
"neonatal epilepsy" is not used to describe neonatal seizures.
Seizures in neonates are relatively common, with variable
clinical manifestations. Their presence is often the first sign of neurological
dysfunction, and they are powerful predictors of long-term cognitive and
developmental impairment.
Pathophysiology:
Seizures occur when a large group of neurons undergo
excessive, synchronized depolarization. Depolarization can result from
excessive excitatory amino acid release (eg,
glutamate) or deficient inhibitory neurotransmitter (eg,
gamma amino butyric acid [GABA]). Another potential cause is disruption of
ATP-dependent resting membrane potentials, which causes a flow of sodium into
the neuron and potassium out of the neuron. Hypoxic-ischemic encephalopathy
disrupts the ATP-dependent sodium-potassium pump and appears to cause excessive
depolarization. It is an important cause of neonatal seizures.
Frequency:
In the
The incidence of seizures is higher in the neonatal period (ie, the first 4 weeks after birth) than in any other age
group.
Internationally:
Incidence is unknown.
Mortality/Morbidity:
Neonatal seizures are a risk factor that markedly increases
rates of long-term morbidity and neonatal mortality.
The presence of neonatal seizures is the best predictor of long-term physical and cognitive deficits.
Race: No racial preponderance is known.
Sex: Sex-based frequency differences have not been
described.
Age:
Neonatal seizures by definition occur within the first 4
weeks of life in a full-term infant and up to 44 weeks from conception for
premature infants.
Seizures are most frequent during the first 10 days of life.
History:
The clinical history provides important clues to the likely
etiology of neonatal seizures.
A family history of neonatal convulsions may suggest that
the infant has a genetic syndrome. Many of these syndromes are considered
benign and frequently disappear within the neonatal period.
In the absence of other etiologies, a family history of
neonatal seizures may suggest a good prognosis.
A detailed pregnancy history is important.
Search for a history that supports TORCH (toxoplasmosis,
rubella, cytomegalovirus, herpes) infections. The
presence of kittens may suggest toxoplasmosis as an etiology.
A history of fetal distress, preeclampsia,
or maternal infection also can provide etiologic clues.
Delivery history is also important.
The type of delivery and the antecedent events should be
documented.
Apgar scores may offer some
guidance concerning etiology, although a low Apgar
score without the need for resuscitation and subsequent neonatal intensive care
is unlikely to be associated with neonatal seizures.
The postnatal history is also significant.
Neonatal seizures in infants with an uneventful antenatal
history and delivery may result from a postnatal cause. A history of
tremulousness may suggest drug withdrawal or neonatal hypocalcemia.
Temperature and/or blood pressure instability may suggest an infection; a
sepsis workup may be required.
A history of rubella or the absence of immunization against
rubella may offer a diagnostic clue. In the
Neonatal seizures are classified as follows:
Most seizures in the neonate are focal,
although generalized seizures have been described in rare instances.
Subtle seizures are more common in full-term than in premature infants. Video EEG studies have demonstrated that most subtle seizures are not associated with electrographic seizures. Examples of subtle seizures include chewing, pedaling, or ocular movements.
Clonic seizures:
These movements most commonly are associated with electrographic seizures. They often involve one extremity or one side of the body. The rhythm of the clonic movements is usually slow, 1-3 movements per second.
Tonic seizures:
These may involve one extremity or the whole body. Focal
tonic seizures involving one extremity often are associated with electrographic
seizures.
Generalized tonic seizures often manifest with tonic extension
of both upper and lower limbs and also may involve the axial musculature in an opisthotonic fashion.
Generalized tonic seizures mimic decorticate posturing; the
majority are not associated with electrographic seizures.
Myoclonic seizures: These may
occur focally in one extremity or in several body parts (in which case they are
described as multifocal myoclonic
seizures).
Focal and multifocal myoclonic seizures typically are not associated with
electrographic correlates.
Generalized myoclonic jerks are
possibly the clinical equivalent of infantile spasms.
Jitteriness must be differentiated from seizures in
neonates.
Jitteriness is not associated with ocular deviation. It is
stimulus sensitive (eg, easily stopped with passive
movement of the limb). The movement resembles a tremor, and no autonomic
changes are associated with it.
Seizures often are associated with ocular deviation and are
not stimulus sensitive. Autonomic changes frequently accompany them. The
movements are clonic, unlike the tremorlike
movements of jitteriness.
Physical:
Infants with neonatal seizures are frequently lethargic
between seizures and often appear ill.
Findings of the neurologic
examination between seizures may be normal.
However, neurologic examination
abnormalities may be seen correlating with a focal or generalized neurologic syndrome.
Causes: The differential diagnosis for neonatal seizures is
voluminous. Important causes include the following:
Seizures resulting from hypoxic-ischemic encephalopathy may
be seen in both term and premature infants. They frequently present within the
first 72 hours of life. Seizures may include subtle, clonic,
or generalized seizures.
Intracranial hemorrhage occurs more frequently in premature
than in term infants. Distinguishing infants with pure hypoxic-ischemic
encephalopathy from those with intracranial hemorrhage often is difficult.
Subarachnoid hemorrhage is more
common in term infants. This type of hemorrhage occurs frequently and is not
clinically significant. Typically, infants with subarachnoid
hemorrhage appear remarkably well.
Germinal matrix-intraventricular
hemorrhage is seen more frequently in premature than in term infants,
particularly in infants born prior to 34 weeks' gestation. Subtle seizures are
seen frequently with this type of hemorrhage.
Subdural hemorrhage is seen in
association with cerebral contusion. It is more common in term infants.
Metabolic disturbances include hypoglycemia, hypocalcemia, and hypomagnesemia.
Less frequent metabolic disorders, such as inborn errors of metabolism, are
seen more commonly in infants who are older than 72 hours. Typically, they may
be seen after the infant starts feeding.
Intracranial infections (which should be ruled out
vigorously) that are important causes of neonatal seizures include meningitis,
encephalitis (including herpes encephalitis), toxoplasmosis, and
cytomegalovirus (CMV) infections. The common bacterial pathogens include
Escherichia coli and Streptococcus pneumoniae.
While most cerebral malformations present with seizures at a
later age, major malformation syndromes are important to consider. Lissencephaly, pachygyria, polymicrogyria, and linear sebaceous nevus syndrome can
present with seizures in the neonatal period.
Benign neonatal seizure syndromes are characterized by the
following:
Benign familial neonatal seizures typically occur in the
first 48-72 hours of life; the seizures disappear by age 2-6 months. A family
history of seizures is usual. Development is typically normal in these infants.
Benign idiopathic neonatal seizures typically present at day
5 of life (ie, fifth day fits) with the vast majority
presenting between days 4 and 6 of life. Seizures are often multifocal.
Cerebrospinal fluid (CSF) analysis is usually unremarkable.
Benign sleep myoclonus: The
clinician should be familiar with this benign condition in which rhythmic
movements (which occur only during sleep) mimic seizures. The condition can be
alarming and may occur focally during non-rapid eye movement (REM) sleep. Video
EEG monitoring shows no electrographic seizures.
Abnormal Neonatal EEG
Benign Neonatal Convulsions
Cerebellar Hemorrhage
EEG Seizure Monitoring
EEG in Common Epilepsy Syndromes
Early Myoclonic Encephalopathy
Epileptiform Discharges
Herpes Simplex Encephalitis
Neonatal Injuries in Child Abuse
Neonatal Meningitis
Seizures and Epilepsy: Overview and Classification
Shuddering Attacks
Subarachnoid Hemorrhage
Subdural Hematoma
Tuberous Sclerosis
Vein of Galen Malformation
Viral Encephalitis
Viral Meningitis
Other Problems to be Considered:
Anoxia
Benign epilepsy syndromes
Mitochondrial cytopathies
Myoclonic epilepsy
Myoclonus
Organic acidurias
Lab Studies:
Serum glucose and electrolytes, including calcium: Transient
neonatal hypocalcemia is a cause of neonatal seizures
during the first 3 weeks of life.
CSF analysis: This should include tests checking for pleocytosis, xanthochromia
(suggestive of blood breakdown products, particularly if jaundice is not
present), lactic acid and pyruvate (for evidence of
mitochondrial cytopathies), polymerase chain reaction
(PCR) for herpes virus, and glucose concentration (low glucose concentration is
suggestive of bacterial meningitis). In the absence of bacterial meningitis,
persistently low CSF glucose concentrations may suggest a glucose transporter
defect.
TORCH (toxoplasmosis, rubella, CMV, herpes) infection
studies
Urine organic acids
Serum amino acid assay
Renal function tests: These tests rule out posthypoxic renal dysfunction.
Imaging Studies:
Cranial ultrasound
Cranial ultrasound is performed readily at the bedside; it
is a valuable tool to quickly ascertain whether intracranial hemorrhage,
particularly intraventricular hemorrhage, has
occurred.
A limitation of this study is the poor detection rate of
cortical lesions or subarachnoid blood.
Cranial CT scan
The disadvantage is that the sick neonate must be
transported to the imaging site.
A distinct advantage is that with modern CT techniques, a
study can be obtained in approximately 10 minutes.
MRI
Cranial MRI is the most sensitive test in determining the
etiology of neonatal seizures, particularly when electrolyte imbalance has been
excluded as a cause for seizures.
A major disadvantage is that it cannot be performed quickly
and, in an unstable infant, it is best deferred until the acute clinical
situation resolves.
Other Tests:
EEG plays a vital role in properly identifying and
differentiating neonatal seizures from nonepileptic
events (see Images 1-3).
Video EEG monitoring may be helpful when infrequent neonatal
seizures persist.
Echocardiography: This study can rule out cardiac hypomotility as a result of more diffuse hypoxia.
Treatment
Medical Care:
Acute neonatal seizures should be treated aggressively. When
clinical seizures are present, a rigorous workup to determine an underlying
etiologic cause should be initiated quickly. The following points should be
attended to:
Electrolyte imbalances should be corrected through a central
venous site. Hypocalcemia should be treated
cautiously with calcium, since leakage of calcium into subcutaneous tissue can
cause scarring.
Obtain EEG when uncertain as to whether the observed events
are epileptic or nonepileptic.
When an inborn error of metabolism is suspected, discontinue
feeding since feeding may exacerbate the seizures and encephalopathy. Institute intravenous solutions.
Once these issues have been addressed, antiepileptic drug
(AED) therapy should be considered. Phenobarbital is the initial drug of
choice. If seizures persist, the use of phenytoin
should be considered.
Consultations:
Neurology consultation is recommended to help with the
evaluation of seizures, EEG, video EEG monitoring, and management of
anticonvulsant medications.
Medication
Antiepileptic
medications should be instituted in an orderly and efficient manner. Correct
hypoglycemia, if present. Initial treatment with phenobarbital
should be considered. If seizures persist, phenytoin
should be added. Persistent seizures may require use of an intravenous
benzodiazepine such as lorazepam or midazolam.
Drug Category:
Anticonvulsants -- These agents prevent seizure recurrence
and terminate clinical and electrical seizure activity.Drug
Name
Phenobarbital
(Luminal, Barbita) -- Important to use minimal amount
required and to wait for anticonvulsant effect to develop before giving second
dose. Start with loading dose and continue with maintenance dosage.
Pediatric Dose Loading dose: 20 mg/kg/d
Maintenance dose: 5-8 mg/kg/d
Contraindications No known contraindications for use in
neonates
Interactions May decrease phenytoin
effects
Pregnancy C - Safety for use during pregnancy has not been
established.
Precautions In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems;
exercise caution in fever, hyperthyroidism, diabetes mellitus, and severe
anemia, since adverse reactions can occur; exercise caution in patients with
myasthenia gravis or myxedema
Drug Name:
Phenytoin (Dilantin)
-- Should be added to phenobarbital if seizures
persist. May act in motor cortex where may inhibit spread of seizure activity.
Activity of brainstem centers responsible for tonic phase of grand mal seizures
also may be inhibited.
Pediatric Dose Initial dose: 20 mg/kg/d
Maintenance dose: 5-8 mg/kg/d
Contraindications No known contraindications for use in
neonates
Interactions Barbiturates may decrease effects
Pregnancy C - Safety for use during pregnancy has not been
established.
Precautions Hemodynamic stability
should be monitored during IV administration
Drug Name
Lorazepam
(Ativan) -- Benzodiazepine anticonvulsant; use in
cases refractory to phenobarbital and phenytoin. By increasing action of GABA, which is major
inhibitory neurotransmitter in brain, may depress all levels of CNS, including
limbic and reticular formation.
Pediatric Dose 0.05-0.1 mg/kg IV, followed by 0.05 mg/kg
increments until seizures controlled
Contraindications No known contraindications for use in
neonates
Interactions Barbiturates may increase CNS toxicity
Pregnancy C - Safety for use during pregnancy has not been
established.
Precautions With concurrent phenobarbital,
monitor blood pressure and respiration
Drug Category: Vitamins -- This agent may be effective in
seizures refractory to medications already discussed. It is essential for
normal DNA synthesis and cell function.Drug Name
Pyridoxine (Nestrex) -- Should be tried in patients not responding to
above regimen. Patients with pyridoxine-dependent seizures respond immediately
to pyridoxine.
Pediatric Dose 50-100 mg IV with EEG monitoring to determine
response
Contraindications No known contraindications for use in
neonates
Interactions None reported
Pregnancy B - Usually safe but benefits must outweigh the
risks.
Precautions None in neonates
Follow-up
Further Inpatient
Care:
Patients with seizures resulting from intracranial
hemorrhage should have head circumference measurements performed daily. A rapid
increase in head circumference may indicate hydrocephalus.
Seizure medication concentrations should be monitored during
the acute period. These drugs often are discontinued between ages 3 and 6
months if further seizures have not occurred. A trend toward earlier discontinuation
has met with good results.
EEG may be helpful in deciding when to stop AEDs.
A general recommendation is to use AEDs
for 3 months.
If the patient remains seizure free then
medications may be tapered gradually.
If the patient is on 2 AEDs then
one should be tapered first before considering withdrawing the other.
If seizures recur, then the patient should be placed back on
AEDs. The patient may be placed on the original AED,
or carbamazepine may be considered.
Further Outpatient
Care:
Neurology outpatient evaluation and follow-up are needed to
decide when to discontinue seizure medications.
Patients require developmental evaluation for early
identification of physical or cognitive deficits. Enrollment in a "birth
to 3" program may be indicated. Patients must be monitored carefully for
development of contractures; strongly consider a physical medicine/physical
therapy referral.
Orthopedic evaluations may be appropriate in infants with
joint deformities.
Transfer:
Mothers in premature labor ideally should be transferred to
a facility with a tertiary neonatal intensive care unit. This is more desirable
than transfer after birth, since later transfers more commonly result in
morbidity.
Complications:
Cerebral palsy
Hydrocephalus
Epilepsy
Spasticity
Feeding difficulties
Prognosis:
Prognosis is determined by etiology for neonatal seizures.
If EEG background is normal, the prognosis is excellent for
seizures to resolve; normal development is likely.
Severe EEG background abnormalities indicate poor prognosis;
such patients frequently have cerebral palsy and epilepsy.
The presence of spikes on EEG is associated with a 30% risk
of developing future epilepsy.
The prognosis following neonatal seizures that result from
isolated subarachnoid hemorrhage is excellent, with
90% of children not having residual neurological deficits.
Patient Education:
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is generally accepted within medical standards at the time of publication.
However, as medical science is constantly changing and human error is always
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Author: Raj D
Raj D Sheth,
MD, is a member of the following medical societies:
Editor(s): Robert
S Rust, Jr, MD, Thomas E Worrell Jr
Professor of Epileptology and Neurology, Co-Director
of FE Dreifuss Child Neurology and Epilepsy Clinics,
University of Virginia School; Clinical and Residency Training, Child
Neurology, University of Virginia Hospital and Clinics; Francisco Talavera, PharmD, PhD, Senior
Pharmacy Editor, eMedicine; Kenneth J Mack, MD, PhD,
Visiting Associate Professor, Department of Neurology, University of Wisconsin
at Madison; Associate Professor and Consultant, Department of Neurology,
Division of Child and Adolescent Neurology, Mayo Medical School; Matthew J
Baker, MD, Consulting Staff, Collier Neurologic
Specialists, Naples Community Hospital; and Nicholas Lorenzo, MD, Chief Editor,
eMedicine Neurology; Consulting Staff, Neurology
Specialists and Consultants
Links:
http://www.emedicine.com/NEURO/topic240.htm
http://professionals.epilepsy.com/page/syndromes_benignseizures.html