Management of Seizures in Pediatrics
Neonatal Seizures (Age ≤1 month)
Phenobarbital should be the first-line antiseizure medication (ASM) for neonatal seizures, regardless of etiology, with the important exception of suspected channelopathy based on family history. 1
Acute Management Algorithm for Neonates
First-Line Treatment:
- Phenobarbital is the established first-line ASM for all neonatal seizures 1
- Exception: If channelopathy is likely due to positive family history (e.g., self-limited neonatal epilepsy, KCNQ2 encephalopathy), use a sodium channel blocker (phenytoin or carbamazepine) as first-line instead 1
Second-Line Treatment (when first-line fails):
The choice depends on clinical context 1:
For most etiologies (HIE, stroke, hemorrhage): Use phenytoin or levetiracetam
- Alternative options: midazolam or lidocaine (less favorable)
If channelopathy suspected based on clinical or EEG features (even without family history): Use sodium channel blocker (phenytoin or carbamazepine) 1
- Choice between phenytoin vs carbamazepine depends on clinical state (critically ill vs stable) and regional drug availability
If cardiac disorders present: Prefer levetiracetam as second-line 1
If vitamin B6-dependent epilepsy suspected (based on clinical/EEG features) OR if seizures persist after second-line ASM without identified etiology: Trial of pyridoxine (add-on to ASM) 1
Important Caveat: The evidence for second-line ASM choice is very low quality, with no placebo-controlled studies and only add-on design trials 1. However, the consensus-based recommendations provide practical guidance for clinical decision-making.
Duration of Treatment for Neonates
Following cessation of acute provoked seizures without evidence of neonatal-onset epilepsy, discontinue ASMs before discharge home, regardless of MRI or EEG abnormalities. 1
This recommendation is critical because:
- Continuing ASM beyond the acute phase does not improve neurodevelopmental outcomes or reduce subsequent epilepsy risk 1
- Phenobarbital has potential adverse effects, so exposure should be minimized 1
- Discontinuation should occur independently of MRI or EEG background abnormalities 1
Adjunctive Neonatal Considerations
- Therapeutic hypothermia reduces seizure burden in neonates with hypoxic-ischemic encephalopathy 1
- EEG monitoring is essential for reliable diagnosis, as clinical observation alone is inadequate except for focal clonic and focal tonic seizures 1
- Treatment of all seizures (both electrographic and electroclinical) is associated with better neurodevelopmental outcomes and reduced likelihood of later epilepsy 1
Febrile Seizures (Beyond Neonatal Period)
Long-term prophylactic antiseizure medications are NOT recommended for simple febrile seizures due to the benign nature of the condition and potential medication side effects outweighing benefits. 2, 3, 4
Acute Management of Febrile Seizures
Acute treatment follows the same principles as epileptic seizures 3, but chronic preventive anticonvulsants should not be used 3, 4.
Why Prophylaxis is Not Recommended
The evidence against routine prophylaxis is compelling 2:
Phenobarbital: While effective at reducing recurrence (only 10% recurrence vs 47% with carbamazepine), it causes significant behavioral disturbances, irritability, and sleep disturbances in 20-40% of patients—severe enough to necessitate discontinuation 2
Valproic acid: Effective (4% recurrence vs 35% placebo), but carries risk of fatal hepatotoxicity (especially in children <2 years, the peak age for febrile seizures), thrombocytopenia, and gastrointestinal disturbances 2
Carbamazepine: Not effective—47% recurrence rate despite therapeutic levels 2
Phenytoin: Not effective even at therapeutic levels 2
Pharmacologic prophylaxis may only be considered for high-risk cases with complex febrile seizures, but this remains controversial given the benign prognosis and medication risks. 4
Status Epilepticus in Children (>1 month old)
For convulsive status epilepticus in children, intramuscular midazolam, intravenous lorazepam, or intravenous diazepam are established as efficacious first-line treatments. 5, 6, 7
Treatment Algorithm for Pediatric Status Epilepticus
Emergent Phase (First-line benzodiazepines): 6, 7
- Intravenous lorazepam (Level A evidence in children) 7
- Intravenous diazepam (Level A evidence in children) 7
- Intramuscular midazolam (Level B evidence in children; superior to IV lorazepam when IV access unavailable in adults) 7
- Intranasal midazolam (Level B evidence in children) 7
- Buccal midazolam (Level B evidence in children) 7
- Rectal diazepam (Level B evidence in children) 7
No significant difference in effectiveness exists between IV lorazepam and IV diazepam 7.
Urgent Phase (Second-line therapy if seizures persist): 6, 7
Options include:
- Phenytoin/fosphenytoin (fosphenytoin preferred over phenytoin based on tolerability, but phenytoin is acceptable) 7
- Phenobarbital
- Levetiracetam
- Valproate sodium
Critical Point: Second therapy is less effective than first therapy, and third therapy is substantially less effective in adults (Level A); in children, second therapy appears less effective with no data on third therapy efficacy 7.
Refractory Phase (if seizures persist): 6
Continuous infusions:
- Midazolam
- Pentobarbital
Important Safety Considerations
Respiratory and cardiac symptoms are the most common treatment-emergent adverse events with IV anticonvulsant administration. However, the rate of respiratory depression in patients treated with benzodiazepines is actually lower than in those treated with placebo, indicating that respiratory problems are an important consequence of untreated status epilepticus (Level A evidence). 7
General Pediatric Epilepsy Management
When to Initiate Maintenance Therapy
Antiepileptic medication is usually initiated after the second epileptic seizure. 3
Diagnostic Approach
Diagnosis requires 3:
- Medical history and clinical examination
- EEG (essential)
- Brain imaging
- Laboratory tests
Suspicion of epilepsy warrants urgent referral to pediatric or child neurology care. 3
Drug Selection
Drug choice is based on seizure type and epilepsy classification. 3 Recent advances include syndrome-specific ASMs 8:
- Cannabidiol for Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex
- Fenfluramine for Lennox-Gastaut and Dravet syndromes
- Everolimus for tuberous sclerosis complex
- Ganaxolone for cyclin-dependent kinase-like deficiency disorder
Alternative Therapies
For drug-resistant epilepsy 3, 8:
- Ketogenic diet may benefit some children
- Surgical treatment should be considered (including laser interstitial therapy)
- Neurostimulation modalities: VNS, responsive neurostimulation, transcutaneous VNS, transcranial direct current stimulation
Common Pitfalls to Avoid
- Do not use prophylactic ASMs for simple febrile seizures—harms outweigh benefits 2, 3, 4
- Do not continue neonatal ASMs beyond discharge for acute provoked seizures without neonatal-onset epilepsy 1
- Do not delay treatment in status epilepticus—efficacy decreases substantially with each subsequent treatment line 7
- Do not rely on clinical observation alone for neonatal seizure diagnosis—EEG confirmation is essential 1
- Do not use carbamazepine or phenytoin for febrile seizure prophylaxis—they are ineffective 2