What is the appropriate acute and follow‑up management for an 18‑40‑year‑old patient presenting with a first generalized tonic‑clonic seizure?

Management of a Single Episode of GTCS in Younger Adults

Do not routinely initiate antiepileptic drugs after a first unprovoked generalized tonic-clonic seizure in patients aged 18–40 who have returned to baseline neurologic status. 1, 2

Acute Emergency Department Management

Immediate Actions if Patient is Still Seizing

• Administer lorazepam 4 mg IV at 2 mg/min immediately for any actively seizing patient, which terminates status epilepticus in approximately 65% of cases 3
• Have airway equipment immediately available before giving benzodiazepines due to respiratory depression risk 3
• If seizures persist after adequate benzodiazepine dosing, escalate to second-line agents: valproate 30 mg/kg IV (88% efficacy, 0% hypotension), levetiracetam 30 mg/kg IV (68–73% efficacy), or fosphenytoin 20 mg PE/kg IV (84% efficacy but 12% hypotension risk) 3

Evaluation for Reversible Causes

• Check fingerstick glucose immediately and correct hypoglycemia—a rapidly reversible cause 3
• Assess for hyponatremia (the most common electrolyte disturbance precipitating seizures), hypoxia, drug toxicity or withdrawal (especially alcohol, benzodiazepines), and CNS infection 3
• Obtain serum glucose and sodium as the only laboratory tests that consistently change acute management of a first unprovoked seizure 3
• Perform pregnancy test in patients of childbearing potential 3

Neuroimaging Strategy

• Obtain emergent non-contrast head CT if any high-risk features are present: age >40 years, recent head trauma, focal seizure onset, fever or persistent headache, anticoagulation use, known malignancy or immunocompromised state, focal neurologic deficit, or persistent altered mental status 3
• CT abnormalities are identified in 23–41% of first-time seizure presentations with high-risk features 3
• If the patient has returned to baseline with normal neurologic exam, no high-risk features, and reliable outpatient follow-up, defer neuroimaging to outpatient MRI, which is more sensitive for epileptogenic lesions 3

EEG Recommendations

• Arrange outpatient EEG for every patient after a first unprovoked seizure, as an abnormal EEG predicts higher risk of seizure recurrence 3
• Obtain emergent EEG only if altered consciousness persists after the seizure to detect non-convulsive status epilepticus 3

Disposition and Follow-Up

Discharge Criteria

• Patients who have returned to their clinical baseline in the emergency department can be safely discharged without admission 3
• Admit if: persistent abnormal neurologic examination, abnormal investigation results requiring inpatient management, failure to return to baseline, or unreliable follow-up 3

Observation Period

• Patients should remain under observation during the highest risk period for early recurrence: more than 85% of early recurrences happen within 6 hours (mean time 121 minutes) 2
• Patients with history of alcohol use disorder combined with prior seizure episodes have the highest early recurrence rate (approximately 25%) 3

Decision Regarding Antiepileptic Drug Initiation

Evidence Against Routine Treatment

The World Health Organization explicitly recommends against routine prescription of antiepileptic drugs after a first unprovoked seizure in both adults and children. 1, 2 This represents the clearest guideline-level recommendation.

• Seizure recurrence risk is only 20–30% in unselected patients, and treatment does not improve long-term outcomes at 5 years 1
• Approximately one-third to one-half of patients with a first unprovoked seizure will have recurrence within 5 years, even with normal MRI and EEG 2
• The number needed to treat (NNT) to prevent a single seizure recurrence within the first 2 years is 14 patients 1, 2
• The majority of recurrences occur in the first year (89% of all recurrences in one prospective study) 4

When to Consider Treatment

Emergency physicians may initiate AED therapy or defer in coordination with neurology when high-risk features are present, as seizure recurrence risk increases to 60–70% in these patients: 1

• Age ≥40 years 2
• History of alcoholism 2
• Hyperglycemia 2
• Glasgow Coma Scale score <15 2
• Abnormal EEG showing generalized spike-wave discharges 5
• Structural brain lesion on imaging 1

Medication Selection IF Treatment Is Indicated

If the decision is made to treat (in consultation with neurology), medication selection depends on seizure type and patient characteristics:

For Primary Generalized Tonic-Clonic Seizures

• Valproate is first-line in males or menopausal women without weight concerns, but is absolutely contraindicated in women of childbearing potential due to teratogenicity and neurodevelopmental risks 1, 6, 7
• Levetiracetam or lamotrigine are viable first-line alternatives, particularly in women of childbearing potential 6, 7
• Topiramate is effective but concerns arise from potential cognitive and memory adverse effects 6, 7
• There is class 1 evidence of efficacy for only four AEDs in controlling primary GTCSs: lamotrigine, levetiracetam, perampanel, and topiramate 6

For Secondarily Generalized Tonic-Clonic Seizures

• Levetiracetam, perampanel, topiramate, and (with less robust data) lamotrigine are supported by pooled analyses or meta-analyses 6

Critical Pitfalls to Avoid

• Do not default to immediate treatment—the guideline-based approach is observation and neurology follow-up, not automatic AED initiation 1, 2
• Do not use valproate in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay 1, 6, 7
• Do not delay anticonvulsant administration if the patient is actively seizing to obtain neuroimaging—CT scanning can be performed after seizure control 3
• Do not skip second-line agents and jump to third-line anesthetic agents (pentobarbital, propofol) until benzodiazepines and a second-line agent have been tried 3

Prognosis and Counseling

• Overall mortality for status epilepticus ranges from 5% to 22%, but this applies to prolonged seizures, not single brief GTCSs 3
• In patients with epilepsy with generalized tonic-clonic seizures alone (EGTCA) who are eventually treated, 14% have seizure recurrence on medication compared with 73% of untreated patients 5
• For patients who remain seizure-free on medication for at least 2 years with absence of generalized spike-wave discharges on EEG, approximately 56% maintain seizure freedom after medication withdrawal 5