# Febrile Seizures and Pediatric Epilepsy

## Overview

Febrile seizures are the most common seizure type in children, affecting 2-5% of children aged 6 months to 5 years. Most febrile seizures are benign, self-limited, and do not indicate epilepsy. Epilepsy affects approximately 0.5-1% of children, and multiple well-defined childhood epilepsy syndromes have been characterized. A key clinical skill is distinguishing benign febrile seizures from epilepsy and identifying which children need further workup.

## Febrile Seizures

### Definition and Classification

A febrile seizure is a seizure associated with fever (38C/100.4F or higher) in a child aged 6 months to 5 years without CNS infection or other identified cause. Simple febrile seizures account for about 75% of cases and are generalized (tonic-clonic), last fewer than 15 minutes, do not recur within 24 hours, and have no postictal focal deficits. Complex febrile seizures make up the remaining 25% and are characterized by focal features, duration of 15 minutes or longer, recurrence within 24 hours, or postictal focal deficits (Todd paralysis). Febrile status epilepticus is defined as a febrile seizure lasting 30 minutes or more.

### Evaluation

#### Simple Febrile Seizure

No routine blood work, EEG, or neuroimaging is needed per AAP guidelines. The focus should be on identifying the source of fever, with viral illness being the most common cause. Lumbar puncture is not routinely recommended but should be considered if meningeal signs are present, the child is unimmunized (especially against Hib and pneumococcus), the child was pretreated with antibiotics, or the clinical appearance is concerning. The 2011 AAP guidelines state that LP should be considered in infants 6-12 months who are deficiently immunized or not immunized.

#### Complex Febrile Seizure

EEG should be considered, though the yield is low; it may be indicated for recurrent complex febrile seizures. Neuroimaging (MRI) should be considered for prolonged focal seizures, persistent neurologic deficit, or recurrent complex seizures. There is a lower threshold for LP, particularly with prolonged postictal states.

### Prognosis and Recurrence

The recurrence risk is approximately 30-35% after a first febrile seizure. Risk factors for recurrence include age younger than 18 months at first seizure, family history of febrile seizures, lower temperature at the time of seizure, and shorter duration of fever before the seizure. The risk of subsequent epilepsy is 2-4% (compared to 1% in the general population) and is higher with complex febrile seizures, neurodevelopmental abnormalities, and family history of epilepsy.

### Management and Parent Counseling

Most febrile seizures stop spontaneously within 2-3 minutes and require only supportive care with recovery positioning. Rescue medication (rectal diazepam at 0.5 mg/kg or intranasal midazolam at 0.2 mg/kg) should be administered for seizures lasting longer than 5 minutes. Antipyretics do not prevent febrile seizure recurrence, as studies show no benefit, though they may be used for comfort. Daily anticonvulsant prophylaxis is not recommended because the risks outweigh the benefits for simple febrile seizures. Intermittent oral diazepam at fever onset reduces recurrence but is associated with sedation and is rarely used. Parent education is critical: families should be reassured about the benign nature of febrile seizures, taught seizure first aid, and told that febrile seizures do not cause brain damage, intellectual disability, or behavioral problems.

<image>Comparison of simple versus complex febrile seizures showing clinical features, evaluation recommendations (LP, EEG, imaging indications), recurrence risk factors, and long-term epilepsy risk for each type, with a decision algorithm for workup based on classification</image>

## Pediatric Epilepsy Syndromes

| Syndrome | Age of Onset | Seizure Type | EEG Pattern | First-Line Treatment | Prognosis |
|----------|-------------|-------------|-------------|---------------------|-----------|
| Childhood Absence (CAE) | 4-10 yr | Brief staring (5-30 sec) | 3 Hz spike-and-wave | Ethosuximide or valproate | 65-70% remit by adolescence |
| Juvenile Myoclonic (JME) | 12-18 yr | Morning myoclonus + GTC | 4-6 Hz polyspike-and-wave | Valproate, levetiracetam, lamotrigine | Lifelong treatment (90% relapse off meds) |
| BECTS (Rolandic) | 3-13 yr | Hemifacial twitching, nocturnal | Centrotemporal spikes | Levetiracetam or carbamazepine (may not need treatment) | Remission by 15-16 yr |
| Infantile Spasms (West) | 3-12 months | Flexor/extensor spasms in clusters | Hypsarrhythmia | ACTH (vigabatrin if TSC) | Poor (50-70% intellectual disability) |
| Lennox-Gastaut | 1-7 yr | Multiple types (tonic, atonic, atypical absence) | Slow spike-and-wave (<2.5 Hz) | Valproate, lamotrigine, clobazam, ketogenic diet | Poor, medication-resistant |

### Childhood Absence Epilepsy (CAE)

Childhood absence epilepsy has an age of onset between 4 and 10 years, peaking at 5-7 years. The seizures are absence seizures consisting of brief staring episodes lasting 5-30 seconds with behavioral arrest and automatisms such as lip smacking and eye blinking. They have abrupt onset and offset, with the child resuming activity immediately and no postictal state. Episodes may occur dozens to hundreds of times daily. The EEG shows pathognomonic 3 Hz generalized spike-and-wave discharges, and hyperventilation is a potent activator that provokes absences in more than 90% of cases. Treatment is ethosuximide (first-line for absence-only epilepsy) or valproate, with lamotrigine as an alternative. Carbamazepine and phenytoin must not be used, as they can worsen absence seizures. The prognosis is favorable, with 65-70% achieving remission by adolescence, though 15-20% develop generalized tonic-clonic seizures.

### Juvenile Myoclonic Epilepsy (JME)

JME has an onset between ages 12 and 18 years and presents with the classic triad of myoclonic jerks (especially in the morning shortly after awakening), generalized tonic-clonic seizures, and sometimes absence seizures. It is precipitated by sleep deprivation, alcohol, photic stimulation, and stress. The EEG shows 4-6 Hz generalized polyspike-and-wave discharges. Treatment is with valproate (most effective but teratogenic, so it should be avoided in females of childbearing potential), levetiracetam, or lamotrigine (which may worsen myoclonus). Seizure control with medication is excellent, but lifelong treatment is usually required because approximately 90% relapse when medication is withdrawn.

### Benign Epilepsy with Centrotemporal Spikes (BECTS/Rolandic Epilepsy)

This is the most common childhood focal epilepsy, with onset between ages 3 and 13 years (peak 7-10). Seizures involve hemifacial (mouth, tongue) twitching, drooling, and speech arrest. They are often nocturnal and may secondarily generalize. The EEG shows centrotemporal (rolandic) spikes activated by sleep. Treatment may not be required if seizures are infrequent and nocturnal only; when treatment is needed, levetiracetam or carbamazepine is used. Remission occurs by age 15-16 years in nearly all cases, hence the "benign" designation.

### Infantile Spasms (West Syndrome)

Infantile spasms onset occurs between 3 and 12 months (peak 4-6 months) and present with the triad of infantile spasms, developmental regression, and hypsarrhythmia on EEG. The spasms are sudden, brief symmetric flexion or extension of the trunk and extremities, occurring in clusters, often upon awakening. The EEG shows hypsarrhythmia, a chaotic, high-voltage, disorganized background with multifocal spikes. Etiologies include structural causes (tuberous sclerosis, cortical malformations), genetic, metabolic, or cryptogenic. Treatment is urgent because delay worsens neurodevelopmental outcomes. ACTH is the first-line treatment for most etiologies, while vigabatrin is first-line for tuberous sclerosis complex. Prednisolone is an alternative, and the ICISS trial suggests that combined ACTH plus vigabatrin may be superior. The prognosis is guarded, with 50-70% having intellectual disability, and many evolving to Lennox-Gastaut syndrome.

### Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome onsets between ages 1 and 7 years and is characterized by multiple seizure types: tonic seizures (most common, especially during sleep), atonic seizures (drop attacks), atypical absence, myoclonic, and tonic-clonic. The EEG shows slow spike-and-wave (less than 2.5 Hz) and paroxysmal fast activity during sleep. Intellectual disability is nearly universal, and the epilepsy is typically medication-resistant. Treatment options include valproate, lamotrigine, clobazam, rufinamide, the ketogenic diet, vagus nerve stimulation, cannabidiol (Epidiolex, FDA-approved), and corpus callosotomy for drop attacks. The prognosis is poor, with persistent seizures and intellectual disability in most patients.

<image>Summary table of major pediatric epilepsy syndromes showing age of onset, seizure type, EEG pattern, first-line treatment, and prognosis for childhood absence epilepsy, juvenile myoclonic epilepsy, benign rolandic epilepsy, infantile spasms (West syndrome), and Lennox-Gastaut syndrome</image>

## First-Line Anticonvulsants in Pediatrics

### Commonly Used Medications

Levetiracetam (Keppra) is a broad-spectrum agent that is well tolerated, with behavioral side effects (irritability, aggression) occurring in about 10% of patients. Valproate (Depakote) is effective for generalized epilepsies but is teratogenic (neural tube defects, contraindicated in pregnancy) and carries risks of weight gain, hepatotoxicity, and pancreatitis; it should be avoided in children under 2 years with metabolic disease due to the risk of fatal hepatotoxicity. Ethosuximide (Zarontin) is first-line for absence seizures only and has no efficacy for tonic-clonic seizures. Carbamazepine and oxcarbazepine are first-line for focal epilepsy but can worsen generalized epilepsy (absence, myoclonic); HLA-B*1502 should be checked in Southeast Asian patients due to Stevens-Johnson syndrome risk. Lamotrigine (Lamictal) is broad-spectrum and generally well tolerated but requires slow titration due to Stevens-Johnson syndrome risk. Topiramate is broad-spectrum but carries cognitive side effects, weight loss, nephrolithiasis, and metabolic acidosis. Cannabidiol (Epidiolex) is FDA-approved for Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex, with a risk of hepatotoxicity when used with concurrent valproate.

## When to Start Treatment

Treatment is generally initiated after a second unprovoked seizure, which defines epilepsy. Treatment may be considered after a first seizure if the EEG is abnormal, there is a structural brain abnormality, seizures are nocturnal, there is a family history of epilepsy, or Todd paralysis is present. The risks of medication must always be weighed against the risks of recurrence.

## Clinical Pearls

Simple febrile seizures do not cause brain damage and do not require anticonvulsant treatment; parent education and reassurance are the most important interventions. Antipyretics do not prevent febrile seizure recurrence, which is a common misconception to address with families. Absence seizures should always be provoked with 3 minutes of hyperventilation during the office visit, as it is a simple, reliable bedside test. Carbamazepine and phenytoin must not be used for absence or myoclonic epilepsies because they can worsen seizure frequency. Infantile spasms are a neurological emergency, and early treatment with ACTH or vigabatrin significantly improves developmental outcomes; referral should not be delayed. JME is a lifelong condition, and patients must be counseled that medication withdrawal almost always results in seizure recurrence.

## Key Controversy: Lumbar Puncture in Febrile Seizures

The 2011 AAP guidelines relaxed LP recommendations, making LP an "option" for febrile seizures in well-appearing children. The debate centers on children 6-12 months with a first complex febrile seizure who are well-appearing. Procalcitonin and other biomarkers may help identify those at very low risk of bacterial meningitis. Post-vaccination febrile seizures (such as after MMR or DTaP) are well recognized and generally benign, with LP rarely indicated. The widespread availability of conjugate vaccines has dramatically reduced bacterial meningitis incidence, lowering the pre-test probability. The current practice trend is to perform LP only when meningeal signs are present or the child appears ill, regardless of seizure complexity.

<image>Decision algorithm for febrile seizure evaluation showing stratification by simple versus complex seizure type, age-based LP considerations, EEG and neuroimaging indications, and the role of immunization status and clinical appearance in guiding workup decisions</image>

## References
- Subcommittee on Febrile Seizures. Febrile Seizures: Guideline for the Neurodiagnostic Evaluation of the Child with a Simple Febrile Seizure (AAP). Pediatrics. 2011;127(2):389-394.
- Shinnar S, et al. Long-Term Outcomes of Children with Febrile Status Epilepticus (FEBSTAT Study). Ann Neurol. 2014;75(2):178-185.
- Glauser T, et al. ILAE Treatment Guidelines: Evidence-Based Analysis of Antiseizure Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes. Epilepsia. 2006;47(7):1094-1120.
- Wirrell EC, et al. Optimizing the Diagnosis and Management of Dravet Syndrome. Pediatr Neurol. 2017;68:18-25.
- Berg AT, et al. Risk of Recurrence After a First Unprovoked Seizure. Epilepsia. 2008;49(Suppl 1):13-18.
- Pavone P, et al. West Syndrome: A Comprehensive Review. Neurol Sci. 2020;41(12):3547-3562.