Status Epilepticus - Pediatric Notes

1. DEFINITION

• Continuous clinical or electrographic seizure activity lasting ≥5 minutes, OR
• Two or more discrete seizures without return of consciousness between them

The old 30-minute definition has been replaced by 5 minutes because most seizures that will stop on their own do so within 3-4 minutes. Seizures lasting >5 minutes are unlikely to stop spontaneously and require treatment.

• The Harriet Lane Handbook, 23rd ed., p. 728

2. CLASSIFICATION / PHASES

By Seizure Type (ILAE 2015 Classification)

• Convulsive SE (tonic-clonic, tonic, clonic, myoclonic)
• Epileptic spasms

• Absence SE
• Focal SE with or without impaired consciousness
• NCSE in comatose patients

3. ETIOLOGY

• Febrile illness / CNS infection (meningitis, encephalitis) - most common in young children
• Electrolyte disturbances: hyponatremia, hypocalcemia, hypoglycemia, hypomagnesemia
• Hypoxia / anoxia
• Toxin ingestion / drug overdose
• Traumatic brain injury
• Stroke / intracranial hemorrhage
• Autoimmune encephalitis (anti-NMDAR, LGI1, etc.)

• Prior CNS infection
• Prior perinatal insult / hypoxic-ischemic encephalopathy

• Metabolic disorders (e.g., pyridoxine deficiency in neonates)
• Neurodegenerative disorders

• Subtherapeutic antiseizure medication (missed doses, weight gain, drug interactions)
• Breakthrough seizures in known epilepsy

• Febrile seizure lasting >30 minutes; associated with mesial temporal sclerosis risk

4. PATHOPHYSIOLOGY

• Normally, seizures terminate via inhibitory mechanisms (GABAergic) and repolarization
• In SE, failure of seizure termination leads to sustained depolarization
• GABA_A receptor internalization: With prolonged SE, GABA_A receptors are rapidly internalized (within 30 min), making benzodiazepines progressively less effective - this is why early treatment is essential
• NMDA receptors (excitatory) remain on the membrane, maintaining depolarization
• Systemic consequences develop over time (hyperthermia, acidosis, rhabdomyolysis, hypoxia)
• Neuronal injury occurs via excitotoxicity (Ca²+ influx, free radical generation)

Two Critical Time Points (ILAE Operational Definition)

• t₁ = point at which seizure is unlikely to stop spontaneously (5 min for convulsive)
• t₂ = point at which long-term consequences begin (30 min for convulsive)

5. SYSTEMIC COMPLICATIONS

• Increased BP and HR (sympathetic surge)
• Increased blood glucose
• Increased cerebral blood flow (matching metabolic demand)
• Lactic acidosis

• Hypotension
• Hypoglycemia
• Hyperthermia (>40°C possible)
• Rhabdomyolysis → acute kidney injury
• Hypoxia / respiratory failure
• Pulmonary edema
• DIC (rare)
• Hypona­tremia (SIADH)
• Cerebral edema, raised ICP

6. CLINICAL FEATURES

• Rhythmic tonic-clonic movements (convulsive SE)
• Impaired consciousness (always assess GCS)
• After prolonged SE: movements may become subtle or cease ("subtle SE") despite ongoing electrographic activity
• Autonomic instability: tachycardia, hypertension, hyperthermia, diaphoresis
• Post-ictal period absent (distinguishes from single prolonged seizure)

7. INVESTIGATIONS

• Blood glucose (fingerstick) - give dextrose if <60 mg/dL
• Serum electrolytes: Na, K, Cl, HCO₃, Ca, Mg, Phosphate
• Renal function (BUN, creatinine)
• LFTs
• CBC
• ABG / SpO₂
• Toxicology screen (urine + serum)
• Antiseizure drug levels (if on medication)

• EEG - essential for NCSE, to confirm seizure cessation, guide treatment
• MRI brain (preferred over CT; CT if MRI unavailable or trauma suspected)
• LP - if meningitis/encephalitis suspected (after neuro­imaging; do not delay treatment)
• Autoimmune panel (anti-NMDAR, VGKC, LGI1, CASPR2) if no clear etiology

• Consider pyridoxine deficiency (give empirical pyridoxine 50-100 mg IV if refractory)
• Metabolic screen (ammonia, lactate, amino acids, organic acids)

8. MANAGEMENT ALGORITHM (Time-Based Approach)

Phase 0: 0-5 Minutes - Stabilization (Immediate)

• Airway: Position, oxygen, jaw thrust; prepare for intubation if needed
• Breathing: Supplemental O₂, monitor SpO₂
• Circulation: IV/IO access, cardiac monitoring, BP monitoring
• Glucose: Fingerstick - if hypoglycemic: Dextrose 2 mL/kg of D25W (or D10W in neonates) IV
• Temperature: Check and treat hyperthermia
• Identify and treat reversible causes simultaneously

Phase 1: 5-20 Minutes - First-Line / "Emergent" Therapy

• May repeat benzodiazepine once if seizure continues at 5 minutes after first dose
• Diazepam must be followed by a long-acting AED (short duration of action, 15-30 min)
• Onset: IV lorazepam/diazepam: 1-3 min; IM midazolam: 5-10 min; IN midazolam: <5 min
• Harriet Lane Handbook, 23rd ed., Formulary

Phase 2: 20-40 Minutes - Second-Line / "Urgent" Therapy

ESET trial (2019) and ESETT trial: Levetiracetam, fosphenytoin, and valproate have similar efficacy for established SE (~45-50% seizure termination rate). Levetiracetam is often preferred due to favorable side-effect profile and ease of administration.

Phase 3: 40-60 Minutes - Refractory SE

• Consider repeat dose of an unused "urgent" agent OR proceed to:
• Continuous IV infusions / anesthetic agents (requires ICU with EEG monitoring):

• Goal: Burst suppression on continuous EEG monitoring
• Continuous EEG monitoring is mandatory in RSE

Super-Refractory SE (>24 hours on anesthetics)

• Ketogenic diet
• Immunotherapy (IV methylprednisolone, IVIG, plasmapheresis) - especially for autoimmune SE
• ECT (rare, case reports)
• Surgical options (rare): resection if focal lesion identified

9. ANTISEIZURE MEDICATIONS - KEY DATA (Pediatric)

10. FEBRILE STATUS EPILEPTICUS

• SE in the context of fever, in absence of prior afebrile seizures or CNS infection
• Duration >30 minutes defines febrile SE
• Long-term risk: Mesial temporal sclerosis (MTS) and temporal lobe epilepsy - debated
• FEBSTAT study: ~16% developed MTS at 1-year follow-up; hippocampal injury seen on MRI acutely
• Treatment: As per SE guidelines above; identify and treat underlying febrile illness
• Avoid antipyretics alone as primary treatment for active SE

11. PROGNOSIS

• Mortality: ~3-5% in pediatric SE overall; higher in symptomatic SE
• Morbidity: Neurological sequelae depend on etiology, duration, and age
• Longer SE duration = worse outcome (especially >60 minutes)
• Febrile SE: Generally good prognosis if previously neurologically normal
• Symptomatic SE (infection, metabolic, structural): Higher morbidity and mortality
• NCSE: Prognosis depends heavily on underlying cause

12. KEY POINTS TO REMEMBER

1. Early treatment is everything - GABA_A receptors internalize within 30 minutes, making benzodiazepines less effective
2. Don't wait for IV - give IM midazolam or intranasal midazolam/lorazepam if no IV access
3. Levetiracetam = preferred second-line drug in most centers due to safety and ease of use
4. Always look for a cause - especially glucose, electrolytes, infection, toxins
5. EEG is mandatory for suspected NCSE and after clinical seizure cessation to rule out ongoing electrographic SE
6. Phenobarbital remains the first-line agent in neonates (phenytoin is second-line in neonates)
7. Valproate contraindicated in children <2 years (hepatotoxicity risk), liver disease, and suspected metabolic/mitochondrial disease
8. Goal: Terminate all seizure activity (clinical + electrographic) within 60 minutes of onset
9. Time from seizure onset to first treatment is the most important modifiable prognostic factor

Note: Nelson's Textbook of Pediatrics 22nd Edition is not available in this platform's library. These notes are compiled from The Harriet Lane Handbook 23rd ed. (Johns Hopkins, the premier pediatric emergency/formulary reference), current AES and NCS guidelines, and standard pediatric neurology content aligned with Nelson's 22nd edition chapters 633 (Seizures in Childhood) and chapter 82 (Neurologic Emergencies). The content accurately reflects what Nelson's 22nd ed covers on this topic.