What is the diagnosis and treatment approach for neonatal convulsions?

Neonatal Convulsions: Comprehensive Management

Causes and Etiologies

Hypoxic-ischemic injury is the dominant cause of neonatal seizures, accounting for 46-65% of cases, with 90% of these seizures occurring within the first 2 days of life. 1

Primary Etiologies by Frequency:

• Hypoxic-ischemic encephalopathy (HIE): 46-65% of all cases, predominantly presenting in the first 48 hours after birth 1
• Intracranial hemorrhage and perinatal ischemic stroke: Combined 10-12% of cases 1
• Infection, genetic disorders, and cortical malformations: More likely when seizures occur beyond day 7 of life 1
• Metabolic derangements: Including hypoglycemia, hyponatremia, hypocalcemia, and hypomagnesemia 2, 3
• Inborn errors of metabolism: Particularly vitamin B6-dependent epilepsy and other metabolic disorders 4, 5
• Channelopathies: Genetic sodium or potassium channel disorders 5

Clinical Timing Patterns:

• Early-onset seizures (days 0-2): Strongly suggest perinatal asphyxia/HIE as the underlying cause 1
• Late-onset seizures (beyond day 7): Shift the differential toward infection, genetic disorders, or malformations of cortical development 1

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Differential Diagnosis

Epileptic Seizure Types (Clinical Classification):

• Subtle seizures (42%): Most common type, including eye deviation, blinking, oral-buccal movements, apnea, or autonomic changes 6
• Clonic seizures (64.3% multifocal, 10.7% focal): Rhythmic jerking movements 6
• Tonic seizures (33.9%): Sustained posturing or stiffening 6
• Myoclonic seizures (16.1% multifocal): Brief, shock-like jerks 6

Critical caveat: 55.4% of neonates present with two or more seizure types simultaneously, and 42.9% demonstrate electroclinical dissociation (clinical seizures without EEG correlate or vice versa) 6

Non-Epileptic Paroxysmal Movements (Must Exclude):

• Jitteriness: Stimulus-sensitive, stops with passive flexion, no eye deviation 3
• Benign neonatal sleep myoclonus: Only occurs during sleep, stops when awakened 3
• Hyperekplexia: Exaggerated startle response 3

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Diagnostic Approach

Immediate Bedside Assessment:

Ensure patent airway, adequate breathing, and circulation; monitor heart rate, blood pressure, temperature, and oxygen saturation continuously. 7

Urgent Laboratory Investigations:

• Point-of-care glucose: Must be checked immediately to exclude hypoglycemia 2
• Electrolytes: Sodium, calcium, magnesium 7
• Complete blood count and blood culture: If infection suspected 7
• Arterial blood gas: To assess for metabolic acidosis 2

Neuroimaging Protocol:

• Head ultrasound: Initial bedside imaging if infant is unstable or MRI unavailable 7
• MRI with diffusion-weighted imaging: Gold standard for identifying etiology; absence of major cerebral lesions is highly predictive of normal neurological outcome 7

Electroencephalography:

Continuous video-EEG monitoring is essential for confirming seizures and guiding treatment, as clinical control does not guarantee electrical seizure cessation. 6, 5

• EEG background pattern is the strongest predictor of outcome: moderately abnormal backgrounds predict 72.2% unfavorable outcomes, markedly abnormal predict 100% unfavorable outcomes 6
• Multifocal and low-frequency focal discharges correlate with worse pharmacological control and unfavorable outcomes 6

Advanced Metabolic and Genetic Testing:

• Metabolic screening: If no clear etiology identified 7
• Genetic testing: Consider if seizures are refractory or suggestive of channelopathy 7, 5
• Trial of pyridoxine (vitamin B6): In neonates with seizures unresponsive to second-line ASM and clinical features suggesting vitamin B6-dependent epilepsy 5

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Treatment Algorithm

Step 1: Stabilization and Correction of Metabolic Abnormalities

• Establish IV/IO access immediately 2
• Correct hypoglycemia: D10%-containing isotonic IV solution at maintenance rate 2
• Correct hypocalcemia and hypomagnesemia: Before initiating anticonvulsants 2
• Treat suspected infection: Begin antibiotics empirically 2

Step 2: First-Line Anticonvulsant Therapy

Phenobarbital is the first-line ASM for neonatal seizures regardless of etiology, except when channelopathy is suspected. 5

• Phenobarbital dosing: Standard loading dose (specific dosing per institutional protocol) 5
• Exception: If channelopathy is likely (e.g., positive family history), use phenytoin or carbamazepine instead 5

Step 3: Second-Line Anticonvulsant Therapy

For seizures not responding to phenobarbital, use phenytoin, levetiracetam, midazolam, or lidocaine as second-line agents. 5

• Levetiracetam: Preferred in neonates with cardiac disorders 5
• Lorazepam (for status epilepticus in infants ≥18 years): 4 mg IV slowly (2 mg/min); if seizures continue after 10-15 minutes, repeat 4 mg dose 8
  • Critical warning: Equipment for airway management must be immediately available; respiratory depression is the most important risk 8

Step 4: Adjunctive Therapies

Therapeutic hypothermia reduces seizure burden in neonates with hypoxic-ischemic encephalopathy. 5

• Initiate cooling protocol if HIE is confirmed 5
• Pentoxifylline: 5-day course (6 hours/day IV) can reverse septic shock in very low birth weight babies 2

Step 5: Refractory Seizures

• Rule out correctable causes: Pericardial effusion, pneumothorax, ongoing blood loss, hypoadrenalism, hypothyroidism, inborn errors of metabolism, congenital heart disease 2
• Hydrocortisone: If adrenal insufficiency suspected (peak cortisol after ACTH <18 μg/dL) 2
• ECMO: Consider in term newborns with refractory shock; current survival rate for newborn sepsis is 80% 2

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Duration of Treatment and Discontinuation

Following cessation of acute provoked seizures without evidence of neonatal-onset epilepsy, discontinue ASMs before discharge home, regardless of MRI or EEG findings. 5

• This applies to acute symptomatic seizures (e.g., HIE, stroke, infection) 5
• Neonatal-onset epilepsy requires long-term treatment with different considerations 9

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Seizure Burden and Outcome

Treating neonatal seizures (including electrographic-only seizures) to achieve lower seizure burden is associated with improved outcomes. 5

• Clinical control of seizures is achieved in >80% of cases, but electrical seizure control occurs in only 62.5% 6
• Higher significant association exists between favorable response to treatment and normal neurological examination at discharge and at 1 year of age 6
• Early identification and treatment are critical for long-term outcomes in acute symptomatic seizures 9

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Critical Pitfalls to Avoid

• Do not rely on clinical observation alone: 42.9% of neonates have electroclinical dissociation; continuous video-EEG is mandatory 6
• Do not assume clinical seizure cessation equals electrical seizure cessation: Only 62.5% achieve electrical control despite clinical control 6
• Do not perform lumbar puncture in comatose infants without experienced physician evaluation: Risk of herniation 2
• Do not delay airway management: Respiratory depression is the primary risk with benzodiazepines and barbiturates 8
• Do not continue ASMs indefinitely for acute symptomatic seizures: Discontinue before discharge if no evidence of neonatal-onset epilepsy 5