Overview
Definition:
Neonatal seizures are characterized by sudden, excessive, synchronous neuronal discharge in the immature brain
They represent an abnormal paroxysmal electrical activity that may or may not be clinically evident, requiring prompt recognition and management due to their association with significant neurological morbidity and mortality.
Epidemiology:
The incidence of neonatal seizures varies widely, reported from 1.5 to 5.7 per 1,000 live births
Premature infants and those with underlying neurological insults are at higher risk
Etiologies include hypoxic-ischemic encephalopathy, stroke, infection, metabolic derangements, genetic causes, and congenital brain malformations.
Clinical Significance:
Neonatal seizures are a medical emergency
They can be a symptom of serious underlying pathology, and ongoing seizure activity can lead to excitotoxicity, neuronal damage, and long-term neurodevelopmental deficits
Accurate diagnosis and timely, effective treatment are crucial for improving outcomes in affected neonates, making this a critical topic for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Subtle seizures are the most common, characterized by ocular blinking or staring, sucking or chewing movements, lip smacking, or brief episodes of apnea
Focal clonic movements, generalized tonic seizures, or myoclonic jerks may also occur
Repetitive, brief, or prolonged episodes are typical.
Signs:
Physical examination may reveal focal clonic movements of the face, limbs, or body
Generalized tonic posturing, automatisms, or subtle changes in behavior and tone can be observed
Vital sign abnormalities such as bradycardia or hypertension may accompany seizures.
Diagnostic Criteria:
Diagnosis relies on clinical observation and confirmation with electroencephalography (EEG)
Clinical signs alone are often unreliable
A diagnosis of neonatal seizure is made when characteristic clinical events are correlated with abnormal EEG discharges
EEG is essential to confirm seizure activity, determine seizure type, and assess response to treatment.
Diagnostic Approach
History Taking:
Key history points include gestational age, perinatal events (e.g., Apgar scores, need for resuscitation), maternal history (infections, drug use), family history of seizures or neurological disorders, and any previous episodes or risk factors
Red flags include premature birth, SGA, birth asphyxia, congenital anomalies, or maternal fever.
Physical Examination:
A thorough physical examination is essential, focusing on neurological assessment (tone, reflexes, cranial nerves), dysmorphic features suggestive of genetic syndromes, signs of infection (fever, rash), and assessment for any systemic abnormalities contributing to seizures
Thorough assessment for subtle seizure manifestations is crucial.
Investigations:
Essential investigations include blood glucose, electrolytes (calcium, magnesium, phosphate), arterial blood gas, complete blood count, liver function tests, blood ammonia, urine analysis, and sepsis workup
Neuroimaging such as cranial ultrasound (initially) and MRI (for structural abnormalities) is vital
EEG is the gold standard for diagnosis and monitoring seizure activity.
Differential Diagnosis:
Conditions to consider include benign neonatal sleep myoclonus, jitteriness (exaggerated startle response), tremors, infantile spasms (if occurring later), breath-holding spells, and gastroesophageal reflux
Differentiating these from true seizures based on clinical presentation and EEG findings is critical.
Management
Initial Management:
Immediate management involves stabilization, including airway maintenance, breathing support, and circulation
Treatment of underlying causes is paramount
this includes correcting metabolic derangements (hypoglycemia, hypocalcemia, hypomagnesemia), treating infections, and managing stroke
Benzodiazepines (e.g., lorazepam) are often used for acute seizure termination.
Medical Management:
First-line antiepileptic drugs (AEDs) for ongoing seizure control include phenobarbital and levetiracetam
Phenobarbital has been historically the drug of choice, but levetiracetam is increasingly favored due to its favorable side effect profile and efficacy
Other AEDs like phenytoin, pyridoxine, and topiramate may be used in refractory cases.
Age Specific Dosing:
Phenobarbital is typically initiated at a loading dose of 15-20 mg/kg intravenously, followed by a maintenance dose of 3-5 mg/kg/day
Levetiracetam is given at a loading dose of 20-60 mg/kg and a maintenance dose of 20-40 mg/kg/day, often divided every 12 hours
Doses are adjusted based on clinical response, EEG findings, and drug levels.
Supportive Care:
Supportive care includes meticulous monitoring of vital signs, neurological status, and cardiorespiratory function
Nutritional support is provided via nasogastric or intravenous routes
Close monitoring for adverse effects of AEDs, such as respiratory depression, hypotension, and lethargy, is crucial
Management of any complications arising from seizures or their treatment is also essential.
Phenobarbital Vs Levetiracetam
Efficacy:
Both phenobarbital and levetiracetam have demonstrated efficacy in terminating neonatal seizures
Studies suggest similar rates of seizure cessation, although head-to-head comparisons with robust methodologies are limited
Levetiracetam may achieve seizure freedom more rapidly in some cases.
Side Effect Profile:
Phenobarbital is associated with significant adverse effects including sedation, respiratory depression, hypotension, and long-term neurodevelopmental concerns such as impaired cognition and behavioral issues
Levetiracetam generally has a more favorable side effect profile, with common adverse effects including irritability, vomiting, and feeding difficulties, which are typically transient and less severe.
Drug Interactions:
Phenobarbital is a potent enzyme inducer and can interact with numerous medications, affecting their metabolism and efficacy
Levetiracetam has minimal hepatic metabolism and is less likely to cause significant drug-drug interactions, making it a potentially safer option in poly-medicated neonates.
Recommendations:
Current guidelines and clinical practice are shifting towards levetiracetam as a preferred first-line agent due to its better safety profile, especially considering potential long-term neurodevelopmental outcomes
Phenobarbital remains a valuable option, particularly in resource-limited settings or when levetiracetam is contraindicated or ineffective.
Complications
Early Complications:
Early complications can include apnea, respiratory depression, hypotension, hypothermia, and recurrent seizures
Status epilepticus, a prolonged seizure episode, is a critical early complication that requires aggressive management to prevent brain injury.
Late Complications:
Long-term sequelae can include cerebral palsy, intellectual disability, epilepsy, and behavioral disorders
The underlying etiology of the seizures significantly influences the long-term prognosis and risk of these complications.
Prevention Strategies:
Prevention strategies focus on identifying and managing risk factors for neonatal seizures, such as prompt treatment of maternal infections, optimizing intrapartum care to prevent birth asphyxia, and early recognition and management of metabolic disturbances
Strict adherence to treatment protocols and monitoring can help prevent recurrent seizures.
Prognosis
Factors Affecting Prognosis:
Prognosis is primarily determined by the underlying etiology of the seizures
Neonates with severe hypoxic-ischemic encephalopathy or congenital brain malformations have a poorer prognosis compared to those with transient metabolic derangements
The duration and frequency of seizures also impact outcomes.
Outcomes:
Approximately 50% of term infants with neonatal seizures have a favorable outcome, with normal neurodevelopment
However, up to 25-30% may have significant neurodevelopmental impairments, and a similar proportion may die
The specific antiepileptic treatment and its effectiveness play a role in mitigating neurological damage.
Follow Up:
Neonates who experience seizures require long-term follow-up to monitor for neurodevelopmental delays, cognitive deficits, behavioral problems, and the development of epilepsy
This includes regular clinical assessments, developmental screening, and potential neuroimaging evaluations
Early intervention services are crucial for optimizing outcomes.
Key Points
Exam Focus:
Understand the clinical spectrum of neonatal seizures, from subtle to focal motor
Differentiate between true seizures and imitators
Know the initial management steps and the role of EEG
Compare phenobarbital and levetiracetam regarding efficacy, side effects, and indications
Identify high-risk neonates and common etiologies.
Clinical Pearls:
Always consider pyridoxine deficiency in unexplained neonatal seizures and administer pyridoxine empirically
Closely monitor for respiratory depression with phenobarbital
Levetiracetam is often the preferred first-line agent due to its better safety profile, especially in neonates with concerning neurodevelopmental trajectories
EEG is indispensable for diagnosis and management decisions.
Common Mistakes:
Mistaking jitteriness for seizures, delaying EEG confirmation, inadequate treatment of underlying metabolic causes, and not recognizing subtle seizure manifestations are common pitfalls
Over-reliance on phenobarbital without considering levetiracetam for its favorable profile is also a point of discussion in contemporary practice.