What is the appropriate management for a patient experiencing random seizures?

Management of Random Seizures

For patients experiencing random (unprovoked) seizures, initiate antiepileptic drug (AED) therapy after a first seizure if they have high-risk features including prior brain injury, epileptiform abnormalities on EEG, or structural lesions on neuroimaging; otherwise, treatment can be deferred until a second seizure occurs. 1

Initial Assessment and Risk Stratification

When evaluating a patient with random seizures, the critical first step is determining whether the seizure was provoked or unprovoked:

• Provoked seizures result from acute reversible causes (hypoglycemia, hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, hemorrhage, withdrawal syndromes) and require treatment of the underlying cause rather than chronic AED therapy 1, 2
• Unprovoked seizures occur without an identifiable acute precipitant and carry higher risk for recurrence, particularly with certain risk factors 1, 3

High-Risk Features Warranting Immediate AED Therapy After First Seizure

The number needed to treat (NNT) to prevent one additional seizure in the first year is approximately 5 for patients with either provoked or unprovoked seizures 1. However, immediate treatment after a first unprovoked seizure is indicated when:

• History of prior brain insult (stroke, traumatic brain injury, CNS infection) - these provide anatomic substrate for recurrent seizures 1, 3
• Epileptiform abnormalities on EEG 1, 3
• Structural lesion on MRI 1, 3
• Situations where a second seizure would have devastating psychosocial consequences (e.g., commercial drivers, pilots) 1

Patients without these high-risk features who have returned to clinical baseline in the ED do not require hospital admission and can be discharged with neurology follow-up. 1

Acute Seizure Management

Active Seizure Treatment

If the patient presents with ongoing seizure activity:

First-line treatment: Administer IV lorazepam 4 mg at 2 mg/min immediately, with 65% efficacy in terminating seizures 1, 4

• Lorazepam is superior to diazepam (65% vs 56% success rate) with longer duration of action 4
• Have airway equipment immediately available before administration due to respiratory depression risk 4
• Check fingerstick glucose simultaneously and correct hypoglycemia 4

Second-line treatment (if seizures continue after adequate benzodiazepine dosing):

The 2024 American Heart Association guidelines and recent high-quality evidence support three equally effective options 1, 4, 5:

• Levetiracetam 30 mg/kg IV (maximum 2500-3000 mg) over 5 minutes: 68-73% efficacy, minimal cardiovascular effects, no cardiac monitoring required 1, 4, 5
• Valproate 20-30 mg/kg IV over 5-20 minutes: 88% efficacy, 0% hypotension risk 1, 4, 5
• Fosphenytoin 20 mg PE/kg IV at maximum rate of 150 PE/min: 84% efficacy but 12% hypotension risk requiring continuous cardiac monitoring 1, 4, 5

The ESETT trial (Class I evidence) found no significant difference in efficacy between these three agents, with seizure cessation rates of 47% for levetiracetam, 45% for fosphenytoin, and 46% for valproate 5. Levetiracetam offers the most favorable safety profile with life-threatening hypotension in only 0.7% versus 3.2% with fosphenytoin and 1.6% with valproate. 5

Status Epilepticus (Seizures >5 minutes)

Refractory status epilepticus (continuing despite benzodiazepines and one second-line agent) requires anesthetic agents 1, 4:

• Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion (80% efficacy, 30% hypotension risk) 1, 4
• Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion (73% efficacy, 42% hypotension risk, requires mechanical ventilation) 1, 4
• Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion (92% efficacy but 77% hypotension risk) 1, 4

Long-Term AED Selection for Epilepsy

Once the decision is made to initiate chronic AED therapy (after second unprovoked seizure or first seizure with high-risk features):

For Partial (Focal) Onset Seizures

Levetiracetam is the preferred initial monotherapy due to:

• Effectiveness as initial monotherapy for partial seizures 3
• Minimal drug interactions 3
• Favorable side effect profile 5, 3
• No requirement for blood level monitoring 3

Starting dose: 500 mg twice daily, titrate by 500 mg every 2 weeks to target 1000-1500 mg twice daily 6

For Generalized Seizures

Valproate, lamotrigine, or topiramate are preferred as they are more effective for generalized seizures than agents targeting partial seizures 3

Critical caveat: Valproate must be avoided in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay 1, 4

Treatment Failure and Referral

If trials of more than two AEDs at adequate doses fail to control seizures, refer to an epilepsy center for surgical evaluation. 3

• Additional AEDs beyond two failed trials are unlikely to be effective 3
• Epilepsy surgery renders 60-70% of patients with temporal lobe epilepsy free of disabling seizures 3
• Mortality rates are 4-7 times higher in people with medically refractory seizures 7

Special Considerations

Seizures in Specific Contexts

Intracerebral hemorrhage (ICH):

• Treat clinical seizures with antiseizure drugs to improve functional outcomes 1
• For impaired consciousness with confirmed electrographic seizures, administer antiseizure drugs to reduce morbidity 1
• Prophylactic antiseizure medication is NOT beneficial in ICH patients without evidence of seizures 1
• Consider continuous EEG monitoring for ≥24 hours in ICH patients with unexplained altered mental status 1

Post-cardiac arrest:

• Treat clinically apparent seizures immediately 1
• Perform EEG promptly for patients not following commands after ROSC 1
• Treatment of nonconvulsive seizures (diagnosed by EEG only) is reasonable 1
• Seizure prophylaxis is NOT recommended in cardiac arrest survivors 1

Common Pitfalls to Avoid

• Do not use phenytoin for alcohol withdrawal seizures - it is ineffective 2
• Do not skip directly to third-line anesthetic agents without trying benzodiazepines and a second-line agent 4
• Do not use neuromuscular blockers alone - they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 4
• Do not assume altered mental status is post-ictal - obtain urgent EEG if patient doesn't awaken within expected timeframe, as nonconvulsive status epilepticus occurs in >50% of cases 4
• Do not delay anticonvulsant administration for neuroimaging in active status epilepticus 4

Monitoring and Follow-Up

• Question patients about seizure occurrences at each follow-up visit 4
• Check serum drug levels to assess compliance if breakthrough seizures occur 4
• Search for precipitating factors (sleep deprivation, alcohol use, medication non-compliance, intercurrent illness) that can trigger breakthrough seizures 4
• Consider EEG to distinguish true epileptic seizures from psychogenic seizures or detect subclinical activity 4

The consequences of uncontrolled seizures are severe, including shortened lifespan, excessive bodily injury, neuropsychological impairment, and social disability. 7 Complete seizure control should be the goal, as the risks of uncontrolled seizures outweigh the risks of aggressive medical or surgical therapy. 7