What is the differential diagnosis and plan for a patient with a history (Hx) of seizures, who had their last seizure episode 2 years ago and presented with a new 2-minute seizure episode today?

Differential Diagnosis and Management Plan for Recurrent Seizure After 2-Year Seizure-Free Period

Immediate Differential Diagnosis

The differential diagnosis must distinguish between provoked (acute symptomatic) seizures requiring urgent intervention versus unprovoked seizures representing breakthrough epilepsy. 1, 2

Provoked (Acute Symptomatic) Seizures - Rule Out First:

• Metabolic derangements: Hypoglycemia, hyponatremia, hypocalcemia, hypomagnesemia 1, 2
• Acute intracranial pathology: Intracranial hemorrhage, stroke, new mass lesion, CNS infection (meningitis/encephalitis) 3, 1
• Toxic/withdrawal states: Alcohol withdrawal, drug intoxication or withdrawal, medication changes 3, 4
• Systemic illness: Sepsis, uremia, hepatic encephalopathy, hypoxia 5
• Medication non-compliance: If patient was on antiepileptic drugs (AEDs), abrupt discontinuation or subtherapeutic levels 6
• Rare presentations: Pulmonary embolism (though <1% of cases) 7

Unprovoked Seizures:

• Breakthrough seizure in known epilepsy: Progression of underlying epileptogenic substrate 3, 1
• New structural lesion: Tumor, vascular malformation, progressive brain injury 3, 8

Immediate Management Plan

Step 1: Initial Stabilization and Assessment (First 30 Minutes)

Ensure patient has returned to clinical baseline with complete neurological examination, as this determines disposition. 3, 1

• Vital signs and airway assessment: Document complete return to baseline mental status 1
• Focused neurological examination: Look specifically for new focal deficits, persistent altered mental status, or signs of increased intracranial pressure 3, 1
• Detailed seizure characterization: Duration (already documented as 2 minutes), focal vs. generalized onset, post-ictal state duration, tongue biting, incontinence 4

Step 2: Mandatory Laboratory Testing

Only glucose and sodium consistently alter acute management and must be checked immediately. 2

• Mandatory for all patients: Serum glucose, serum sodium, pregnancy test (if woman of childbearing age) 1, 2
• Additional testing based on clinical context:
  • Complete metabolic panel if history suggests metabolic derangement (vomiting, diarrhea, dehydration) 2
  • Calcium and magnesium if known cancer or renal failure 2
  • Drug screen if substance abuse suspected 4
  • AED levels if patient was on maintenance therapy 3

Step 3: Neuroimaging Decision Algorithm

Emergent head CT without contrast is required if ANY high-risk features are present: 3, 1, 2

High-risk features requiring emergent CT:

• Age >40 years 3
• New focal neurological deficits that don't rapidly resolve 1, 2
• Persistent altered mental status (not returned to baseline) 1, 2
• History of malignancy or immunocompromised state 3, 2
• Fever or signs of meningeal irritation 3, 1
• Recent head trauma 3
• Anticoagulation use 3
• Persistent headache 3
• Focal seizure onset before generalization 3

For patients without high-risk features who have returned to baseline: Deferred outpatient MRI is acceptable if reliable follow-up is ensured 3, 1

Step 4: Lumbar Puncture Indications

Perform lumbar puncture (after head CT) only when specific concerns exist: 1, 2

• Fever with meningeal signs suggesting meningitis/encephalitis 1, 2
• Immunocompromised patients to rule out CNS infection 1, 2
• Not indicated for routine uncomplicated seizure evaluation 2

Step 5: Seizure Recurrence Risk Assessment

The mean time to seizure recurrence is 121 minutes (median 90 minutes), with >85% of early recurrences occurring within 6 hours of ED presentation. 3, 1, 2

Risk stratification for early recurrence (within 24 hours): 3, 1

• Overall 24-hour recurrence rate: 19% 3, 2
• Nonalcoholic patients with new-onset seizures: 9.4% (lowest risk) 3, 1
• Alcoholic patients with seizure history: 25.2% (highest risk) 3, 1
• Excluding alcohol-related events and focal CT lesions: 9% recurrence 3, 2

Additional risk factors for recurrence: 3, 1

• Age >40 years
• Alcoholism
• Hyperglycemia
• Glasgow Coma Scale <15
• Abnormal neurological examination

Step 6: Disposition Decision

Emergency physicians need not admit patients with unprovoked seizures who have returned to their clinical baseline in the ED. 3, 1

Discharge criteria (all must be met): 3, 1, 2

• Patient has returned to clinical baseline
• Normal neurological examination
• No high-risk features identified
• Reliable follow-up arranged
• No concerning laboratory or imaging findings requiring inpatient management

Admission criteria (any present): 3, 1, 2

• Persistent abnormal neurological examination or focal deficits
• Not returned to baseline mental status
• Abnormal investigation results requiring inpatient management
• Identified acute symptomatic cause requiring hospitalization
• Social concerns preventing safe discharge

Step 7: Antiepileptic Drug Decision

For this patient with history of seizures (last episode 2 years ago), the decision depends on whether they were previously on AEDs: 3, 1

If patient was on AEDs and stopped:

• Restart previous AED immediately as this represents breakthrough seizure in known epilepsy 3
• Check AED levels if available to assess compliance 3
• Counsel on gradual withdrawal risks 6

If patient was never on AEDs (had single seizure 2 years ago):

• This second unprovoked seizure now meets criteria for epilepsy diagnosis 3, 8
• Initiate AED therapy as risk of recurrence increases substantially from one-third to three-quarters after 2-3 seizures 3
• Number needed to treat to prevent single seizure in first year: approximately 5 3

If acute symptomatic (provoked) seizure identified:

• Do not start AEDs - treat underlying cause only 3, 9
• AEDs are not indicated for provoked seizures 9, 5

Step 8: Outpatient Follow-Up Arrangements

Arrange neurology follow-up within 1-2 weeks for: 1

• EEG (if not done emergently)
• MRI brain with epilepsy protocol (if deferred from ED)
• AED selection and titration if indicated
• Driving restrictions counseling
• Seizure precautions education

Critical Pitfalls to Avoid

• Do not assume alcohol withdrawal seizures without thorough evaluation - this should be a diagnosis of exclusion, especially in patients with prior seizure history 1, 2
• Do not miss alternative diagnoses - approximately 28-48% of suspected seizures have alternative diagnoses including syncope, nonepileptic seizures, or panic attacks 2
• Do not discharge patients with persistent altered mental status or focal deficits - these require admission and further workup 1, 2
• Do not start AEDs for provoked seizures - treat the underlying cause only 3, 9
• Do not miss structural lesions - neuroimaging is essential, though timing can be deferred if low-risk 3, 1
• Do not overlook medication non-compliance - if patient was on AEDs, check levels and assess adherence 3
• Do not forget pregnancy testing - mandatory for all women of childbearing age 1, 2