Status Epilepticus

Risk factors

• Known epilepsy with AED noncompliance (most common cause in epileptics)
• Acute stroke, intracerebral hemorrhage, TBI
• CNS infection (meningitis, encephalitis, abscess)
• Brain tumor
• Metabolic: hyponatremia, hypoglycemia, hypocalcemia, uremia, hepatic failure
• Drug intoxication (cocaine, tramadol, bupropion, isoniazid) or withdrawal (alcohol, benzodiazepines)
• Hypoxic-ischemic injury (post-cardiac arrest)
• Eclampsia in pregnancy
• Autoimmune / paraneoplastic encephalitis (NMDA receptor antibodies)

Pathophysiology

Persistent seizure activity causes time-dependent receptor trafficking: GABA-A receptors are internalized (explaining benzodiazepine failure with delay), while NMDA receptors are externalized (driving excitotoxicity). The result is increasing pharmaco-resistance and ongoing neuronal injury through calcium influx, mitochondrial dysfunction, and excitotoxicity — the longer SE lasts, the harder it is to stop and the more permanent the damage.

Clinical presentation

Differential diagnosis

• Psychogenic non-epileptic status — Asynchronous movements, eyes forcibly closed, lack of postictal confusion, retained consciousness, normal EEG
• Movement disorder / dystonia — Sustained or repetitive movements without altered awareness; no EEG abnormality
• Decerebrate / decorticate posturing — From brainstem injury; not seizure activity
• Severe metabolic encephalopathy — Asterixis, multifocal myoclonus, no organized seizure activity on EEG
• Nonconvulsive status epilepticus — Altered mental status / coma without convulsions — EEG mandatory in any unexplained coma

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Seizure ≥5 min<br/>or recurrent without recovery] --> B[ABCs, O2, IV, glucose<br/>thiamine if at risk]
  B --> C[First-line: IV lorazepam 4 mg<br/>or IM midazolam 10 mg<br/>may repeat × 1]
  C --> D{Seizure stopped?}
  D -->|Yes| E[Maintenance AED<br/>workup etiology]
  D -->|No, 20-40 min| F[Second-line IV AED:<br/>levetiracetam 60 mg/kg<br/>OR fosphenytoin 20 PE/kg<br/>OR valproate 40 mg/kg]
  F --> G{Seizure stopped?}
  G -->|Yes| E
  G -->|No, >40 min| H[Refractory SE:<br/>intubate, anesthetic infusion<br/>midazolam, propofol, or pentobarb]
  H --> I[Continuous EEG<br/>titrate to seizure suppression<br/>or burst-suppression]

Treatment

Complications

• Mortality (10-30% acutely; higher with refractory SE)
• Permanent neurologic injury, cognitive decline
• Hypoxia, aspiration pneumonia
• Rhabdomyolysis, acute kidney injury
• Hyperthermia, lactic acidosis
• Fractures (vertebral compression), tongue laceration
• Cardiac arrhythmias, neurogenic pulmonary edema
• Propofol infusion syndrome (rhabdomyolysis, metabolic acidosis, cardiac dysfunction) with prolonged high-dose propofol

PANCE pearls

• 5-minute rule: treat as SE at 5 min for generalized convulsive seizures — do not wait.
• Underdose of benzodiazepine is the most common error — lorazepam 4 mg (or 0.1 mg/kg) is the correct adult dose.
• Nonconvulsive SE must be considered in any patient with unexplained altered mental status — get a stat EEG.
• Always check glucose first; give thiamine before glucose in alcoholics to avoid precipitating Wernicke encephalopathy.
• ESETT trial (NEJM 2019): levetiracetam, fosphenytoin, and valproate are equally effective for second-line therapy.

References

• AES 2016 — Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus (Glauser et al., Epilepsy Currents 2016)
• ESETT Trial — Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (Kapur et al., NEJM 2019)
• ILAE 2015 — A Definition and Classification of Status Epilepticus (Trinka et al., Epilepsia 2015)
• RAMPART Trial — Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus (Silbergleit et al., NEJM 2012)