What is the recommended evaluation and treatment plan after a first unprovoked seizure in an adult, including choice of antiepileptic drug and duration of therapy?

Treatment After First Seizure

For adults with a first unprovoked seizure who have returned to baseline without evidence of brain disease or injury, antiepileptic medication should NOT be initiated in the emergency department. 1, 2

Risk Stratification Framework

The decision to treat hinges on distinguishing between provoked versus unprovoked seizures and identifying risk factors for recurrence:

Provoked Seizures

• Do not initiate antiepileptic drugs for provoked seizures (metabolic derangement, drug/alcohol intoxication or withdrawal, acute systemic illness). 1
• Treat the underlying precipitating condition only. 1
• Note that even provoked seizures carry an 11.2% risk of subsequent unprovoked seizure at 2 years, higher than the general population, but this still does not warrant immediate treatment. 3

Unprovoked Seizures Without Risk Factors

• Do not initiate antiepileptic drugs in the ED for patients with normal neurologic exam, no history of brain disease/injury. 1, 2
• The WHO explicitly recommends against routine prescription of antiepileptic drugs after a first unprovoked seizure. 2
• Recurrence risk is approximately 30-40% within 5 years, but immediate treatment only prolongs time to second seizure without changing 5-year outcomes. 1, 4
• The number needed to treat to prevent one recurrence in the first 2 years is 14 patients. 1, 2

Unprovoked Seizures With Risk Factors

• May initiate antiepileptic medication in the ED or defer in coordination with neurology for patients with remote history of brain disease or injury (stroke, traumatic brain injury, tumor, CNS infection). 1
• Risk factors that substantially increase recurrence risk to 60-70% include: 4
  • Remote neurologic insult or structural brain lesion on imaging 4
  • Epileptiform abnormalities on EEG 4
  • Age ≥40 years 2
  • History of alcoholism 2
  • Glasgow Coma Scale <15 2

Required Evaluation

Immediate Assessment

• Glucose level is essential, as hyperglycemia increases early recurrence risk. 2
• Electrolytes only if history/exam suggests metabolic derangement (vomiting, diarrhea, dehydration, failure to return to baseline). 1
• Toxicology screening if drug exposure or substance abuse suspected. 1

Neuroimaging

• Brain MRI is preferred over CT for characterizing epileptogenic lesions. 1
• Emergent imaging indicated if focal deficit persists or patient has not returned to baseline within several hours. 1
• Non-urgent MRI should be obtained for all first seizures to identify structural abnormalities that modify recurrence risk. 4

EEG

• Outpatient EEG is recommended as part of the neurodiagnostic evaluation. 1
• Epileptiform abnormalities increase recurrence risk even with normal imaging (hazard ratio 2.2). 3

Observation Period

• Patients should be observed for at least 6 hours after the seizure, as 85% of early recurrences occur within this timeframe (mean time to recurrence 121 minutes). 2
• Patients who return to baseline need not be admitted unless risk factors are present. 1

When Treatment IS Initiated

First-Line Medication Selection

• Levetiracetam 500 mg twice daily is recommended as first-line monotherapy for its favorable pharmacokinetic profile and fewer adverse effects. 5, 4
• Alternative standard options include carbamazepine, phenytoin, or lamotrigine for partial-onset seizures. 4
• Valproate must be avoided in women of childbearing potential due to teratogenicity. 2, 5

Duration of Therapy

• If a second seizure never occurs, the question of treatment duration becomes moot—the patient had a single seizure, not epilepsy. 6
• If a second seizure occurs (confirming epilepsy diagnosis), treatment duration is typically 2+ years of seizure freedom before considering withdrawal, but this decision requires neurology follow-up. 4

Critical Pitfalls to Avoid

• The default should be observation and neurology follow-up, not immediate treatment, as per WHO guidelines. 2
• Do not treat based solely on patient/family anxiety—treatment does not improve long-term prognosis and exposes patients to medication risks. 1, 4
• Do not confuse "high recurrence risk" with "need for immediate ED treatment"—even high-risk patients can have treatment deferred to outpatient neurology within days to weeks. 1
• Recognize that treating 14 patients to prevent one recurrence in 2 years means 13 patients receive unnecessary medication with potential adverse effects. 1, 2

Disposition and Counseling

• Arrange outpatient neurology follow-up within 1-2 weeks for all first seizures. 5
• Counsel about driving restrictions per local laws (typically 3-12 months seizure-free required). 4, 7
• Advise about safety precautions: avoid swimming alone, heights, operating heavy machinery, and sleep deprivation. 4, 7
• Provide seizure first-aid education to patient and family. 4