Treatment of Infantile Seizures
The treatment of infantile seizures depends critically on the seizure type and underlying etiology, with phenobarbital as first-line therapy for most neonatal seizures, ACTH or oral steroids for infantile spasms, and no prophylactic anticonvulsants for simple febrile seizures.
Neonatal Seizures (0-29 days)
First-Line Treatment
- Phenobarbital should be the first-line antiseizure medication for neonatal seizures regardless of etiology 1
- The exception is when a channelopathy is suspected (e.g., family history suggests genetic sodium or potassium channel disorder), in which case phenytoin or carbamazepine should be used instead 1
- Neonatal seizures most commonly result from hypoxic-ischemic injury (46-65%), intracranial hemorrhage, or perinatal stroke (10-12%) 2
Second-Line Options
- For seizures not responding to phenobarbital, use phenytoin, levetiracetam, midazolam, or lidocaine as second-line agents 1
- In neonates with cardiac disorders, levetiracetam may be preferred as the second-line medication 1
- Lidocaine is effective for refractory seizures as second- or third-line treatment, though data are limited 3
Special Considerations
- Therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy 1
- A trial of pyridoxine should be attempted in neonates with clinical features of vitamin B6-dependent epilepsy whose seizures are unresponsive to second-line medications 1
- Treating both clinical and electrographic-only seizures to achieve lower seizure burden may be associated with improved outcomes 1
Discontinuation Strategy
- Following cessation of acute provoked seizures without evidence of neonatal-onset epilepsy, antiseizure medications should be discontinued before discharge home, regardless of MRI or EEG findings 1
Infantile Spasms (Peak Incidence 4-7 Months)
Urgent Treatment Approach
- Clinical suspicion supported by EEG (ideally prolonged) is central to diagnosis 4
- ACTH is preferred for short-term control of infantile spasms 4
- Oral steroids (prednisone or prednisolone) are probably effective for short-term control 4
- A shorter interval from onset of spasms to treatment initiation may improve long-term neurodevelopmental outcome 4
Important Caveat for Cardiac Risk
- In children with infantile spasms being considered for steroid management, consult with cardiology due to risk of cardiomyopathy 2
Alternative Therapies
- Vigabatrin has been shown effective, particularly in tuberous sclerosis-associated infantile spasms 5
- Valproate has efficacy of approximately 25-40%, but carries high risk of fatal hepatotoxicity in very young infants 5
- The ketogenic diet is the treatment of choice for epilepsy related to glucose transporter 1 deficiency syndrome and pyruvate dehydrogenase deficiency 4
Prognosis Context
- 70-90% of patients with infantile spasms develop mental retardation 5
- 20-50% develop Lennox-Gastaut syndrome, one of the most difficult epilepsy syndromes to treat 5
Febrile Seizures (6-60 Months)
Acute Management
- Focus on preventing injury: help the person to the ground, place in recovery position, and clear the surrounding area 6
- Most febrile seizures are self-limited, resolving spontaneously within 1-2 minutes 6
- Activate emergency medical services for seizures lasting >5 minutes, first-time seizures, multiple seizures without return to baseline, or seizures with traumatic injuries, breathing difficulties, or choking 2, 6
Critical "Do Not" Actions
- Never restrain a person having a seizure 2
- Never put anything in the mouth or give food, liquids, or oral medicines during a seizure or when the person has decreased responsiveness after a seizure 2
Long-Term Management
- Neither continuous nor intermittent anticonvulsant therapy is recommended for children with one or more simple febrile seizures 2, 6
- This recommendation is based on the principle that potential toxicities of anticonvulsants (valproic acid's rare fatal hepatotoxicity, phenobarbital's hyperactivity and irritability, diazepam's lethargy and risk of masking evolving CNS infection) outweigh the relatively minor risks of simple febrile seizures 6
Antipyretic Use
- Antipyretics (acetaminophen, ibuprofen, paracetamol) do not prevent febrile seizures or reduce recurrence risk, though they may improve comfort during febrile illness 2, 6
- This is a common pitfall—parents often believe fever control prevents seizures, but evidence clearly shows it does not 2
Recurrence Risk
- Children younger than 12 months at first simple febrile seizure have approximately 50% probability of recurrence 2
- Children older than 12 months have approximately 30% probability of a second febrile seizure 2
- Risk of developing epilepsy is extremely low (approximately 1% by age 7), though slightly higher than the general population, and is likely due to genetic predisposition rather than structural brain damage 2, 6
General Principles for Infantile Epilepsies
Referral Timing
- Patients should be referred from primary or secondary to tertiary care after failure of one antiseizure drug (standard care), with optimal care being referral of all infants after presentation with a seizure 4
- Infants with recurrent seizures warrant urgent assessment for initiation of antiseizure drugs 4
- Infantile encephalopathies should have rapid introduction and increment of antiseizure drug dosage 4
Diagnostic Workup
- Neuroimaging is recommended at all levels of care for infants presenting with epilepsy, with MRI recommended as the standard investigation at tertiary level 4
- Brain MRI should be obtained in cases of rapid increase in head growth, infantile spasms, changes in neurologic examination, and regression of skills 2
- EEG if there is suspicion of seizure activity, with accurate seizure classification using clinical history and EEG to guide medical management 2