Neonatal Seizures: A Comprehensive

Review
Abstract
Neonatal seizures are a significant neurological emergency, often indicating underlying conditions that
can lead to long-term consequences if not promptly identified and managed. This review examines the
various etiologies, including hypoxic-ischemic encephalopathy (HIE), intracranial hemorrhage, stroke,
infections, metabolic disturbances, congenital brain malformations, and genetic syndromes. A systematic
approach to both the workup and management of neonatal seizures is provided, with a focus on
stabilization, comprehensive diagnostic testing, targeted treatment, and continuous monitoring. The
review aims to equip healthcare providers with the knowledge necessary to effectively diagnose and
manage neonatal seizures, ultimately improving outcomes for affected infants.

Introduction
Neonatal seizures are a critical indicator of neurological dysfunction, occurring in approximately 1 to 5
per 1,000 live births. The highest incidence is within the first week of life, making early detection and
intervention crucial. Seizures in neonates often signal underlying conditions such as hypoxic-ischemic
encephalopathy (HIE), intracranial hemorrhage, or metabolic disturbances. Proper identification and
management are essential to mitigate potential brain injury and optimize long-term
neurodevelopmental outcomes.

Etiology of Neonatal Seizures

Neonatal seizures can arise from a wide range of etiologies, each with distinct clinical implications.
Understanding these underlying causes is essential for targeted diagnosis and treatment. The following
table outlines the primary etiologies in descending order of frequency, along with estimated relative
frequencies.

Table 1: Etiologies of Neonatal Seizures in Descending Order of Frequency

Estimated Relative
Category Specific Causes Frequency

Hypoxic-Ischemic Perinatal asphyxia, leading to brain injury and seizures ~40-60%

Encephalopathy

Intracranial Hemorrhage Intraventricular hemorrhage, subdural hemorrhage, ~15-20%

subarachnoid hemorrhage

Stroke Perinatal arterial ischemic stroke, cerebral sinovenous ~10-15%

thrombosis

Infections Meningitis, encephalitis, congenital infections (e.g., TORCH ~10-15%

infections)

Metabolic Disturbances Hypoglycemia, hypocalcemia, hypomagnesemia, inborn ~5-10%

errors of metabolism

Congenital Brain Lissencephaly, polymicrogyria, agenesis of the corpus ~5%

Malformations callosum

Genetic and Epileptic Ohtahara syndrome, Early Infantile Epileptic ~2-5%

Syndromes Encephalopathy, benign familial neonatal convulsions
Hypoxic-Ischemic Encephalopathy (HIE) remains the most common cause of neonatal seizures, typically
presenting within the first few days of life. Intracranial hemorrhage, particularly in preterm infants, is
another frequent cause, often presenting with tonic or clonic seizures. Stroke, including perinatal arterial
ischemic stroke and cerebral sinovenous thrombosis, is a significant cause in term infants, often leading
to focal seizures. Infections, such as meningitis or encephalitis, and metabolic disturbances like
hypoglycemia, are also common causes that can be treated effectively if identified early. Congenital
brain malformations and genetic syndromes, though less common, are critical to consider, especially in
cases of recurrent or refractory seizures.

Seizure Types and Associated Conditions

Neonatal seizures can be categorized into several types, each associated with specific underlying
conditions. Recognizing the type of seizure can provide valuable diagnostic clues and guide treatment
decisions.
Tonic Seizures: Frequently associated with HIE, tonic seizures are common in the first few days
following a hypoxic event. They can also be seen in severe intracranial hemorrhage, particularly
involving the brainstem, and in early-onset epileptic encephalopathies like Ohtahara syndrome,
where they are often accompanied by a burst-suppression pattern on EEG.
Clonic Seizures: These are often related to focal cerebral lesions, such as stroke or localized
intracranial hemorrhage. Clonic seizures may also be a sign of metabolic disturbances like
hypoglycemia or hypocalcemia, where they can be generalized or multifocal.
Myoclonic Seizures: Myoclonic seizures are commonly seen in inborn errors of metabolism, such as
nonketotic hyperglycinemia and mitochondrial disorders. They are characteristic of metabolic
encephalopathies and severe neonatal epilepsy, such as Early Myoclonic Encephalopathy (EME).
Subtle Seizures: Subtle seizures, which can manifest as eye deviations, chewing movements, or
autonomic signs like apnea, are often seen in HIE. They can also be present in CNS infections, such
as meningitis or encephalitis, and in genetic epileptic syndromes, where EEG can provide additional
diagnostic information.
Atonic Seizures: Characterized by a sudden loss of muscle tone, atonic seizures are frequently seen
in genetic epileptic syndromes like West syndrome or Lennox-Gastaut syndrome and may also
occur in metabolic encephalopathies.
Mixed Seizure Types: These are often observed in severe epileptic encephalopathies, such as
Ohtahara syndrome and EME, where a combination of tonic, clonic, and myoclonic seizures occurs.
Mixed seizure types can also be seen in metabolic disorders, often accompanied by signs of
metabolic dysfunction such as lactic acidosis or hyperammonemia.

Stepwise Approach to the Workup of Neonatal Seizures

A thorough and systematic workup is essential for identifying the underlying cause of neonatal seizures
and guiding appropriate treatment. The following table provides a stepwise approach to the diagnostic
workup of neonatal seizures.

Table 2: Diagnostic Steps in the Workup of Neonatal Seizures

Step Investigations Purpose

Initial Assessment ABC stabilization, neurological Stabilize the neonate and assess the
and Stabilization examination immediate neurological condition.

Blood Glucose Point-of-care blood glucose test Identify and correct hypoglycemia, a
Measurement common cause of neonatal seizures.

Electrolytes and Serum electrolytes, blood gas analysis Detect electrolyte imbalances (e.g.,
Blood Gas Analysis hypocalcemia) and metabolic acidosis.
Step Investigations Purpose

Complete Blood Blood sample for CBC Evaluate for signs of infection, anemia, or
Count (CBC) thrombocytopenia.

Sepsis Workup Blood cultures, urine cultures, lumbar Rule out sepsis or meningitis as potential
puncture if indicated causes of seizures.

Neuroimaging Cranial ultrasound, MRI, or CT scan Identify structural brain abnormalities,

hemorrhage, or stroke.

EEG Continuous video EEG monitoring, Confirm diagnosis of seizures, differentiate

amplitude-integrated EEG (aEEG) from non-epileptic events, assess seizure
burden.

Metabolic and Expanded metabolic panel, genetic Identify inborn errors of metabolism or
Genetic Testing testing (chromosomal microarray, genetic causes of seizures.
targeted epilepsy gene panels)

Lumbar Puncture Cerebrospinal fluid analysis (glucose, Diagnose or rule out meningitis,
protein, cell count, culture, viral PCR) encephalitis, or metabolic disturbances
affecting the CNS.

The initial steps in the workup of neonatal seizures involve stabilizing the infant and conducting a
detailed neurological examination. Hypoglycemia, a common and treatable cause of seizures, must be
assessed and corrected immediately. Electrolyte and blood gas analyses are crucial for detecting
metabolic disturbances that can precipitate seizures. A complete blood count and sepsis workup are
necessary to rule out infections, which are significant contributors to neonatal seizures. Neuroimaging,
such as cranial ultrasound or MRI, is vital for identifying structural abnormalities like hemorrhage or
stroke. Continuous EEG monitoring is essential for confirming the presence of seizures and
differentiating them from non-epileptic events. Metabolic and genetic testing should be considered in
cases where the cause is not immediately apparent, as these can reveal inborn errors of metabolism or
genetic syndromes. A lumbar puncture may be necessary if CNS infection is suspected.

Stepwise Approach to the Management of Neonatal Seizures

Managing neonatal seizures requires a comprehensive approach that addresses both the immediate
seizure activity and the underlying cause. The following table outlines the steps involved in the
management of neonatal seizures.

Table 3: Management Steps for Neonatal Seizures

Step Interventions Purpose

Stabilization and Airway management, oxygen Stabilize vital functions and correct any
Supportive Care supplementation, temperature control, metabolic derangements.
blood glucose management

First-Line Phenobarbital (20 mg/kg IV loading dose), Control seizures with first-line
Anticonvulsant Levetiracetam (10-20 mg/kg IV loading anticonvulsants.
Therapy dose)

Second-Line Phenytoin (15-20 mg/kg IV loading dose), Manage refractory seizures with
Anticonvulsant Midazolam or Lidocaine (continuous second-line agents.
Therapy infusion in refractory cases)

Treatment of Correct metabolic imbalances, treat Address the root cause of the seizures
Underlying Etiology infections, manage intracranial hemorrhage to prevent recurrence.
or stroke
Step Interventions Purpose

Ongoing Monitoring Continuous EEG monitoring, consider Monitor seizure activity and minimize
and Neuroprotection neuroprotective strategies (e.g., therapeutic further neurological damage.
hypothermia in appropriate cases)

Long-Term Weaning anticonvulsants, Ensure optimal long-term outcomes

Management and neurodevelopmental follow-up, monitoring through careful management and
Follow-Up for long-term sequelae monitoring of the neonate's
development.

Family Support and Parental counseling, providing information Support and educate the family
Education on condition, treatment, and prognosis throughout the treatment process and
long-term care of the infant.

The management of neonatal seizures begins with the stabilization of vital functions, including airway
management, oxygen supplementation, and temperature control. Phenobarbital remains the most
commonly used first-line anticonvulsant, though Levetiracetam is gaining favor due to its safety profile.
For seizures that are refractory to first-line treatment, second-line agents such as Phenytoin, Midazolam,
or Lidocaine may be required. Treating the underlying cause of the seizures, whether metabolic,
infectious, or structural, is crucial to preventing recurrence. Continuous EEG monitoring is vital for
assessing seizure activity and guiding treatment decisions. Neuroprotective strategies, such as
therapeutic hypothermia, may be considered in appropriate cases. Long-term management involves the
gradual weaning of anticonvulsants, close monitoring of neurodevelopment, and ongoing support and
education for the family to ensure the best possible outcomes for the infant.

Conclusion
Neonatal seizures are a significant indicator of neurological dysfunction, requiring prompt diagnosis and
intervention to prevent long-term neurological damage. While advances in neuroimaging, EEG
monitoring, and genetic testing have improved our ability to diagnose and manage these seizures,
continued research is needed to better understand their underlying mechanisms and to develop more
effective treatments. Early intervention, tailored treatment strategies, and comprehensive long-term
follow-up are essential in the management of neonates with seizures to optimize their developmental
outcomes.

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