Seizures in Children: Detailed Overview

1) Definitions and key concepts

• Seizure: transient occurrence of signs/symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
• Epilepsy (ILAE concept): usually diagnosed when any of the following apply:
  1. At least 2 unprovoked seizures >24 hr apart, or
  2. 1 unprovoked seizure with high recurrence risk, or
  3. Diagnosis of an epilepsy syndrome.
• Acute symptomatic (provoked) seizure: occurs in temporal association with CNS insult/metabolic-toxic trigger (fever, hypoglycemia, meningitis, trauma, etc.).
• Febrile seizure: seizure with fever (typically 6 months to 5 years) without CNS infection or prior afebrile seizures.

---

2) Classification (practical pediatric approach)

A. By onset

1. Focal onset
   • Aware or impaired awareness
   • Motor (clonic, tonic, automatisms, atonic, etc.) or nonmotor
   • May progress to bilateral tonic-clonic
2. Generalized onset
   • Motor: tonic-clonic, tonic, clonic, myoclonic, atonic, epileptic spasms
   • Nonmotor: absence (typical/atypical)
3. Unknown onset
   • When beginning is unwitnessed or unclear

B. Epilepsy types in children

• Focal epilepsy
• Generalized epilepsy
• Combined generalized and focal
• Unknown

C. Epilepsy syndrome framework

---

3) Etiology (age-dependent)

• Structural: malformations of cortical development, hypoxic-ischemic injury, stroke, tumor, trauma
• Genetic: channelopathies, developmental and epileptic encephalopathies
• Infectious: meningitis, encephalitis, neurocysticercosis (region-dependent)
• Metabolic: hypoglycemia, hypocalcemia, hyponatremia, inborn errors
• Immune: autoimmune encephalitis
• Unknown

• Neonate: hypoxic-ischemic encephalopathy, intracranial hemorrhage, stroke, infection, metabolic errors
• Infant: infantile spasms, genetic epilepsies, post-infectious causes
• School-age/adolescent: genetic generalized epilepsies, focal epilepsies, trauma, tumors (less common)

---

4) Clinical features

• Motor: stiffening, jerking, gaze deviation, asymmetric posturing
• Nonmotor: behavioral arrest, staring, autonomic signs, sensory phenomena
• Focal signs: head/eye version, unilateral clonic movements, speech arrest
• Postictal period: confusion, sleepiness, Todd paresis
• Mimics: syncope, breath-holding, reflux events, parasomnias, psychogenic nonepileptic events, tics, migraine phenomena

---

5) Initial evaluation of a child with seizure

A. Immediate stabilization

• Airway, breathing, circulation
• Position lateral, suction if needed
• Rapid bedside glucose
• Stop prolonged seizure promptly

B. Focused history

• Description/video of event, duration, focality, fever, trauma, toxins, sleep deprivation
• Developmental history and regression
• Family history of seizures/epilepsy
• Drug exposure/adherence

C. Examination

• Full neurologic exam
• Signs of infection/meningismus
• Neurocutaneous markers
• Head circumference in younger children

---

6) Investigations

• Glucose immediately in all prolonged/altered events
• Electrolytes, calcium, magnesium, CBC, infection workup as indicated
• EEG:
  • Usually recommended after first unprovoked seizure (timing depends on stability/resources)
  • Helps classify seizure type and estimate recurrence risk
• Neuroimaging:
  • Urgent CT/MRI if focal deficits, trauma, persistent altered state, concern for raised ICP, suspected structural lesion
  • MRI preferred nonurgent modality for focal epilepsy or abnormal neuro exam/development
• Lumbar puncture if concern for CNS infection
• Metabolic/genetic testing in selected children (early onset, developmental delay, refractory seizures, dysmorphism, family pattern)

---

7) Acute management (including status epilepticus principles)

1. First line (benzodiazepine)
   • IV lorazepam or diazepam
   • If no IV: intranasal/buccal midazolam or rectal diazepam
2. Second line (urgent control ASM)
   • Levetiracetam, fosphenytoin/phenytoin, or valproate (selection based on age/comorbidity/contraindications)
3. Refractory status
   • PICU, continuous EEG, anesthetic infusions per protocol

---

8) Long-term treatment

• Decision to start antiseizure medication (ASM) after first unprovoked seizure depends on recurrence risk, EEG, MRI, syndrome, and family preference.
• Choose ASM by seizure type/syndrome and adverse-effect profile:
  • Broad-spectrum options often used for generalized epilepsies
  • Focal-onset options for focal epilepsies
• Monitor:
  • Seizure control
  • Cognition, behavior, school performance
  • Medication adverse effects and adherence
• Drug-resistant epilepsy (failure of 2 appropriate ASMs):
  • Evaluate for epilepsy surgery
  • Consider ketogenic diet, vagus nerve stimulation, other advanced therapies

---

9) Febrile seizures (high-yield pediatric topic)

• Simple febrile seizure: generalized, <15 min, single in 24 hr, neurologically normal child
• Complex febrile seizure: focal and/or >15 min and/or recurrent within 24 hr
• Most are benign, with excellent neurodevelopmental prognosis.
• Routine neuroimaging and routine EEG generally not needed for classic simple febrile seizures.
• Counsel parents on fever management and seizure first aid; rescue plans for prolonged events in selected cases.

---

10) Counseling, safety, and prognosis

• Seizure first aid: protect from injury, side position, no objects in mouth, time the seizure, emergency plan for prolonged seizure
• Water safety, bathing supervision, heights/fire precautions, sleep hygiene
• School action plan and rescue medication instructions
• Prognosis depends on cause, syndrome, developmental status, and treatment response
• Many childhood epilepsies remit; developmental and epileptic encephalopathies carry higher morbidity

---

11) Red flags needing urgent specialist/emergency action

• First seizure with persistent altered consciousness
• Focal neurologic deficit
• Signs of CNS infection
• Head trauma or suspected toxic ingestion
• Recurrent seizures without recovery between events
• Seizure >5 minutes or respiratory compromise

---

1. Exam-oriented notes (tables and mnemonics),
2. Flowchart for first seizure workup in pediatrics, or
3. Age-wise differential diagnosis table (neonate to adolescent).

---

Status Epilepticus (SE)

---

1. Definition

For clinical practice: treat at the 5-minute mark — do not wait for 30 minutes.

---

2. Classification

By seizure type:

By treatment response:

---

3. Etiology

Common causes by age group:

General etiologic categories (ILAE):

• Structural: malformations, stroke, tumor, trauma, HIE
• Infectious: meningitis, encephalitis, NCC
• Immune: anti-NMDAR, anti-LGI1, MOG-associated
• Metabolic: hypoglycemia, hyponatremia, hypocalcemia, inborn errors
• Genetic: Dravet syndrome, POLG mutations (valproate contraindicated), FIRES
• Unknown: largest category

---

4. Pathophysiology

• Normally, seizures terminate due to inhibitory mechanisms (GABA-A receptor activity, endogenous adenosine, potassium efflux).
• In SE, these fail due to:
  • GABA-A receptor internalization (time-dependent) → benzodiazepines lose efficacy with time
  • Persistent NMDA receptor activation → excitotoxicity
  • Failure of inhibitory interneurons
• Consequences of prolonged SE:
  • Cerebral: neuronal death (hippocampus, thalamus, neocortex), excitotoxic injury
  • Systemic: hyperpyrexia, hypoxia, hypoglycemia, lactic acidosis, autonomic dysregulation, rhabdomyolysis, aspiration
• This is why time = brain — treat immediately

---

5. Clinical Phases of Convulsive SE

Key point: Cessation of motor activity does NOT mean seizure has stopped — EEG monitoring is essential in late SE.

---

6. Staged Treatment Protocol

Immediate (all stages)

• ABCs: airway, breathing, oxygenation
• Cardiac monitoring, pulse oximetry
• IV/IO access
• Fingerstick glucose immediately — treat hypoglycemia
• Vitals, temperature

---

Stage 1: First-line — Benzodiazepines (0–5 min)

Give 2 doses maximum before advancing — each with 5 min gap if seizure persists.

---

Stage 2: Second-line — Established SE (20–40 min)

Evidence (ECLIPSE trial, KONECT trial): Levetiracetam, valproate, and fosphenytoin have comparable efficacy (~50%) for established SE — choice should be guided by context.

---

Stage 3: Refractory SE (>40–60 min, after 2nd-line failure)

---

Stage 4: Super-Refractory SE (≥24 hr despite anesthesia)

• Pyridoxine/pyridoxal phosphate (especially in infants — rule out B6-dependent epilepsy)
• Ketogenic diet (via nasogastric tube)
• Immunotherapy if autoimmune SE suspected (IVIG, steroids, rituximab)
• Hypothermia (investigational)
• Surgical intervention (in selected structural causes)
• Continuous EEG-guided management

---

7. Special Considerations

Febrile Status Epilepticus

• Most common SE in children under 5
• Generally good prognosis for simple febrile SE
• Prolonged febrile SE associated with hippocampal injury and mesial temporal lobe epilepsy (MTLE) later
• Treat with same protocol; LP if CNS infection suspected

Neonatal SE

• Often subtle (eye deviation, lip smacking, cycling movements)
• First line: Phenobarbital 20 mg/kg
• Treat underlying cause aggressively (glucose, calcium, pyridoxine)

Dravet Syndrome

• Avoid phenytoin/fosphenytoin (sodium channel blocker — worsens)
• Benzodiazepines + stiripentol/clobazam; ketamine for RSE

FIRES (Febrile Infection-Related Epilepsy Syndrome)

• Rare, devastating new-onset RSE in previously healthy school-age child
• Preceded by febrile illness
• Ketogenic diet, anakinra, and immunotherapy may be beneficial

---

8. Investigations During SE

---

9. Complications

---

10. Prognosis

• Mortality of CSE in children: ~3–5% overall; higher in symptomatic etiology
• Morbidity: depends on etiology (febrile SE has good prognosis; structural/infectious SE carries worse outcomes)
• Recurrence risk: up to 30–40% in symptomatic cases
• Long-term epilepsy: higher risk after SE, especially prolonged febrile SE or structural etiology

---

Quick-Reference Algorithm

Seizure ≥ 5 min
        ↓
ABCs + glucose + monitor
        ↓
Benzodiazepine (×2 doses, 5 min apart)
  → IV lorazepam 0.1 mg/kg OR IM midazolam 0.2 mg/kg
        ↓ fails
2nd-line ASM (choose one):
  → Levetiracetam 40–60 mg/kg IV  [preferred]
  → Valproate 20–40 mg/kg IV
  → Fosphenytoin 20 mgPE/kg IV
        ↓ fails
PICU + continuous EEG
  → Midazolam infusion / Propofol / Pentobarbital
        ↓ fails ≥24 hr
Super-refractory SE protocol:
  → Ketogenic diet, immunotherapy, ketamine, pyridoxine

---