What is the initial approach for an outpatient seizure workup?

Outpatient Seizure Workup

For adults and adolescents with new-onset seizures presenting in the outpatient setting, obtain serum glucose and sodium levels, perform an EEG, and arrange MRI brain imaging as the core diagnostic triad. 1

Initial Laboratory Testing

The laboratory workup should be targeted and efficient:

• Check serum glucose and sodium levels in all patients, as these are the most frequent metabolic abnormalities that directly cause seizures and alter acute management 1, 2
• Obtain a pregnancy test for all women of childbearing age, as this affects diagnostic testing, medication selection, and disposition decisions 1, 2
• Consider toxicology screening if drug exposure or substance abuse is suspected, particularly in adolescents and young adults 1
• Additional tests (CBC, comprehensive metabolic panel, calcium, magnesium) should only be obtained when specific clinical findings suggest them—routine broad laboratory panels are not evidence-based 1

Neuroimaging

MRI is the preferred imaging modality for outpatient seizure evaluation 1, 2. This provides superior detection of structural abnormalities including cortical malformations, mesial temporal sclerosis, and subtle lesions that CT may miss.

However, emergent CT head without contrast is indicated if any high-risk features are present 1:

• Recent head trauma
• Persistent altered mental status or failure to return to baseline
• New focal neurological deficits
• Persistent headache
• History of cancer or immunocompromised state
• Anticoagulation use
• Age >40 years
• Focal onset seizure before generalization
• Fever suggesting CNS infection

Approximately 22% of patients with normal neurologic examinations still have abnormal imaging, so neuroimaging should not be deferred based solely on normal examination 1.

Electroencephalography (EEG)

EEG is recommended as part of the neurodiagnostic evaluation for all patients with apparent first unprovoked seizure 1. Abnormal EEG findings predict increased risk of seizure recurrence and help classify seizure type and epilepsy syndrome 1, 3.

Lumbar Puncture

Lumbar puncture is NOT routinely indicated for uncomplicated first-time seizures 1. It should be reserved for:

• Concern for meningitis or encephalitis (fever, persistent headache, meningismus) 1
• Immunocompromised patients 1, 2

Risk Stratification for Recurrence

The decision to initiate antiepileptic medication depends on recurrence risk assessment:

High-risk features for recurrence include 1:

• Abnormal neurological examination
• Abnormal EEG with epileptiform discharges
• Structural brain lesion on imaging
• Remote symptomatic seizures (prior brain insult)
• Todd's paralysis

Low-risk patients (normal examination, normal EEG, no structural lesion) have a 1-year recurrence risk of 14-36% 1. The mean time to first recurrence is 121 minutes (median 90 minutes), with 85% occurring within 6 hours 1, 2.

Antiepileptic Drug Initiation

Antiepileptic drug treatment after a single seizure reduces 1-2 year recurrence risk but does not affect long-term recurrence rates or remission rates 1. Starting treatment for a single seizure exposes patients to medication adverse effects without proven mortality or morbidity benefit 1.

Therefore, patients with a first unprovoked seizure who have returned to baseline, have normal neurologic examination, and normal initial workup do not require immediate antiepileptic medication 1, 2. Treatment decisions should be made in consultation with neurology based on individual recurrence risk.

Common Pitfalls to Avoid

• Failing to identify hypoglycemia or hyponatremia as reversible causes of seizures 1
• Assuming all seizure-like events are epileptic seizures—syncope, psychogenic non-epileptic seizures, and other conditions can mimic seizures 4, 5
• Overlooking alcohol withdrawal as a cause, especially in first-time seizures 4
• Missing subtle focal features that suggest structural brain abnormalities requiring imaging 4
• Incomplete medication history leading to failure to identify drugs that lower seizure threshold 4

Disposition

Patients who have returned to clinical baseline with normal neurologic examination may be managed as outpatients with close neurology follow-up 1, 2. Admission should be considered if abnormal neurologic examination persists, investigation results are abnormal, or the patient has not returned to baseline 1, 2.