How should a new‑onset seizure be assessed, worked up, and managed acutely, including stabilization, laboratory and imaging studies, electroencephalogram, and decisions about initiating antiepileptic therapy?

New-Onset Seizure: Assessment, Workup, and Acute Management

For patients presenting with a new-onset seizure who have returned to baseline, perform neuroimaging when feasible in the ED (preferably CT for rapid assessment), obtain serum glucose and sodium levels, and defer antiepileptic drug initiation unless there is a remote history of brain disease or injury. 1, 2

Initial Stabilization and Assessment

Immediate Actions

• Ensure airway patency, breathing, and circulation while assessing for ongoing seizure activity 3
• Check fingerstick glucose immediately at bedside, as hypoglycemia is a rapidly reversible cause requiring immediate intervention 2, 4
• Obtain IV access and draw initial laboratory studies during stabilization 2

Confirm the Event Was Actually a Seizure

• Look for tonic-clonic movements that are prolonged and begin simultaneously with loss of consciousness, which strongly suggest true seizure 2
• Be aware that 28-48% of suspected first seizures have alternative diagnoses including syncope, nonepileptic seizures, or panic attacks 2
• Document whether the patient has truly returned to baseline neurologic status, as this guides all subsequent decisions 1

Laboratory Evaluation

Essential Tests for All Patients

• Serum glucose and sodium are the only laboratory tests that consistently alter acute management and should be obtained in all patients 2, 4
• Pregnancy test for all women of childbearing age (reached menarche), as this affects testing, disposition, and antiepileptic drug selection 2, 4

Selective Additional Testing Based on Clinical Context

• Calcium and magnesium levels in patients with known cancer, renal failure, or alcohol-related seizures 2, 4
• Toxicology screening if drug exposure or substance abuse is suspected, though routine screening has not proven beneficial 2, 4
• Complete metabolic panel only when specific clinical findings suggest metabolic abnormalities (vomiting, diarrhea, dehydration, failure to return to baseline) 1, 4

Common Pitfall: Avoid ordering extensive laboratory panels routinely, as only glucose and sodium abnormalities consistently require immediate intervention in the ED. 2

Neuroimaging Strategy

Emergent CT Head Without Contrast Indicated For:

Perform emergent non-contrast head CT when any of the following high-risk features are present: 1, 2

• Age >40 years
• Focal neurologic deficits (including Todd's paralysis)
• Persistent altered mental status or failure to return to baseline
• Recent head trauma
• History of malignancy or immunocompromised state
• Fever or persistent headache
• Anticoagulation use
• Focal seizure onset before generalization

CT rapidly identifies structural pathology requiring urgent intervention including intracranial hemorrhage, stroke, mass lesions, and hydrocephalus, with 23-41% of first-time seizure patients having abnormal findings. 1, 2

Deferred Outpatient MRI Acceptable For:

Low-risk patients may have neuroimaging deferred to outpatient setting when ALL of the following are met: 1, 2

• Returned to baseline neurologic status
• Normal neurologic examination
• No high-risk features listed above
• Reliable follow-up arrangements confirmed

MRI is the preferred imaging modality for non-emergent evaluation as it is more sensitive than CT for detecting epileptogenic lesions, particularly in temporal and orbitofrontal regions. 1, 2, 4

Important Caveat: Even with normal neurologic examination, 22% of patients still have abnormal imaging, so outpatient MRI should be arranged for all first-seizure patients. 2

Electroencephalography (EEG)

Emergent EEG Indications:

• Persistent altered consciousness after seizure to detect nonconvulsive status epilepticus 2
• Refractory status epilepticus for treatment monitoring 2

Non-Emergent EEG:

• EEG is recommended as part of the neurodiagnostic evaluation for all patients with apparent first unprovoked seizure, though this can be arranged as outpatient 1, 2
• Abnormal EEG findings predict increased risk of seizure recurrence and should influence treatment decisions 2

Lumbar Puncture

Lumbar puncture should be performed primarily when there is concern for meningitis or encephalitis, particularly in patients with: 1, 2

• Fever with meningeal signs
• Immunocompromised state (after head CT to exclude mass effect)
• Persistent altered mental status without alternative explanation

Routine lumbar puncture is NOT indicated for uncomplicated first-time seizures. 2

Disposition Decisions

Safe for Discharge When:

Emergency physicians need not admit patients with a first unprovoked seizure who have returned to their clinical baseline in the ED. 1, 2

Consider Admission For:

• Persistent abnormal neurologic examination 2
• Abnormal investigation results requiring inpatient management 2
• Patient has not returned to baseline 2
• Unreliable follow-up or social concerns 1

Seizure Recurrence Risk Data:

• Overall 24-hour recurrence rate is 19%, decreasing to 9% when alcohol-related events and focal CT lesions are excluded 2
• Mean time to first recurrence is 121 minutes (median 90 minutes), with >85% of early recurrences occurring within 6 hours 2
• Nonalcoholic patients with new-onset seizures have the lowest recurrence rate (9.4%) 2

Antiepileptic Drug Initiation

Do NOT Initiate AED in ED For:

Emergency physicians need not initiate antiepileptic medication in the ED for: 1

• Provoked seizures (treat the precipitating medical condition instead)
• First unprovoked seizure without evidence of brain disease or injury

MAY Initiate AED in ED For:

Emergency physicians may initiate antiepileptic medication, or defer in coordination with other providers, for: 1

• First unprovoked seizure WITH remote history of brain disease or injury (stroke, traumatic brain injury, tumor, CNS disease >7 days prior)

Rationale:

• Approximately one-third to one-half of patients with first unprovoked seizure will have recurrence within 5 years 1
• Initiating treatment after first seizure prolongs time to subsequent event, but outcomes at 5 years are no different 1
• Number needed to treat is 14 patients to prevent a single seizure recurrence within first 2 years 1
• For patients with remote symptomatic seizures (history of CNS injury), seizure recurrence rate is higher and treatment is considered appropriate after one seizure 1

Critical Point: Starting antiepileptic drugs for a single seizure exposes patients to medication adverse effects without proven mortality or morbidity benefit. 2

Special Populations and Considerations

Alcohol-Related Seizures:

Alcohol withdrawal seizures should be a diagnosis of exclusion, especially in first-time seizures—always search for symptomatic causes before labeling as withdrawal seizures. 2

Classification for Documentation:

Classify seizures as either provoked or unprovoked: 2

• Provoked: occurring within 7 days of acute insult (electrolyte abnormalities, withdrawal, toxic ingestions, encephalitis, CNS mass)
• Unprovoked: occurring without acute precipitating factors
• Remote symptomatic: from CNS/systemic insults >7 days prior (stroke, traumatic brain injury)

Driving Restrictions:

Counsel patients against driving until seizure-free for at least 3 months (specific restrictions vary by state). 5