What is the clinical approach for a patient with a new onset unprovoked seizure?

Clinical Approach to New-Onset Unprovoked Seizure

Patients with a first unprovoked seizure who have returned to their clinical baseline in the emergency department do not require hospital admission and should not be started on antiepileptic medications immediately. 1

Initial Assessment and Risk Stratification

History and Physical Examination

The evaluation must distinguish between provoked (acute symptomatic) and unprovoked seizures, as this fundamentally changes management. 1

Key historical elements to document:

• Pre-ictal warning signs or aura 2
• Duration of seizure activity (critical for severity assessment) 2
• Post-ictal state and time to return to baseline 2
• Recent illness, fever, head trauma, sleep deprivation 2
• Alcohol use/withdrawal or drug use 2
• Past history of stroke, traumatic brain injury, or CNS disease (these convert the seizure to "remote symptomatic" and increase recurrence risk) 1

Physical examination priorities:

• Complete neurological examination with attention to focal deficits 2
• Vital signs, particularly fever suggesting infection 2
• Signs of intoxication or withdrawal 2

Laboratory Testing

Mandatory for all patients:

• Serum glucose 3, 4
• Serum sodium 3, 4
• Pregnancy test for all women of childbearing age 3, 4

Additional testing based on clinical context:

• Complete blood count if infection suspected 3
• Basic metabolic panel including BUN, creatinine, electrolytes 3
• Calcium and magnesium, especially in older adults or those on diuretics 3
• Magnesium level specifically for suspected alcohol-related seizures 3, 4
• Extended electrolyte panel (including phosphate) for patients with renal insufficiency, malnutrition, or diuretic use 3
• Drug screen for first-time seizures with suspected substance use 3
• Toxicology screening if medication toxicity suspected 3

Important caveat: Laboratory testing has low yield in patients who have returned to baseline neurological status, with most abnormalities predictable by history and physical examination. 4

Neuroimaging

Head CT scan is recommended for all older adults with new-onset seizures to evaluate for structural lesions. 3

MRI is preferred over CT when available, particularly for:

• Patients with focal neurological deficits 3
• When CT is negative but clinical suspicion for structural abnormality remains high 3
• All patients with first unprovoked seizure as part of outpatient workup 5

Emergent neuroimaging required for:

• Postictal focal deficits that do not quickly resolve 4
• Immunocompromised patients 3
• Fever or signs of meningeal irritation (after head CT, proceed to lumbar puncture) 3, 4

Disposition and Admission Decisions

Discharge is appropriate when:

• Patient has returned to clinical baseline (GCS 15) 1
• No concerning features on history or examination 1
• First unprovoked seizure with no high-risk features 1

Risk factors requiring more extensive evaluation or admission consideration:

• Age ≥40 years 1
• Alcoholism 1
• Hyperglycemia 1
• GCS <15 1
• Abnormal neurological examination or focal deficits 3
• Fever or signs of infection 3
• Immunocompromised status 3

Early seizure recurrence data: Most early recurrences (>85%) occur within 360 minutes (6 hours), with mean time of 121 minutes. Nonalcoholic patients with new-onset seizures have the lowest early recurrence rate (9.4%). 1

Antiepileptic Medication Decision

For first unprovoked seizure, the strategy of waiting until a second seizure before initiating antiepileptic medication is considered appropriate. 1

Rationale: While treatment within days to weeks after a first seizure prolongs time to subsequent event, outcomes at 5 years are no different. The number needed to treat to prevent a single seizure recurrence within the first 2 years is 14 patients. 1

Exceptions where treatment after first seizure is appropriate:

• History of CNS injury (stroke, traumatic brain injury) - these patients have higher recurrence rates 1
• Remote symptomatic seizures (CNS insult >7 days prior) 1
• Structural brain lesions identified on imaging 6
• Epileptiform abnormalities on EEG 6

For provoked seizures: Treat the underlying cause; antiepileptic drugs are not indicated. 6

Outpatient Follow-up

All patients with first unprovoked seizure require:

• Electroencephalography (EEG) 7, 5
• Epilepsy protocol-specific MRI with thin-cut coronal slices 5
• Referral to epilepsy specialist or neurology 8
• Screening for mental health conditions 8
• Neurocognitive testing when deficits suspected or MRI shows involvement of cognitive brain regions 8

Driving restrictions: A seizure diagnosis severely limits driving privileges, though laws vary by state. 7

Critical Pitfalls to Avoid

• Do not assume alcohol withdrawal seizures without thorough evaluation - this should be a diagnosis of exclusion, especially in first-time seizures. 3, 4
• Do not routinely start antiepileptic medications after first unprovoked seizure - this does not affect long-term outcomes or remission rates. 1, 7
• Do not discharge patients with persistent altered mental status or focal deficits - these require admission and further workup. 1, 3
• Do not miss structural lesions - neuroimaging is essential in adults with new-onset seizures. 3, 7