What serum studies should be included in the workup of a patient presenting with a seizure and no known medical history?

Serum Studies in Seizure Workup

Essential Laboratory Tests for All Patients

For any adult patient presenting with a seizure and no known medical history, obtain serum glucose and sodium levels immediately—these are the only two laboratory tests with sufficient evidence to warrant routine use and are the most frequent metabolic abnormalities that require immediate intervention. 1, 2, 3, 4

Core Mandatory Tests

• Serum glucose: Hypoglycemia is the most commonly identified unsuspected metabolic cause of seizures, though rare (1-2 cases per 163-247 patients studied). However, when present, it requires immediate correction and is often not predicted by history and physical examination alone. 1, 5

• Serum sodium: Hyponatremia is the second most common metabolic abnormality, with approximately 1 unsuspected case per 98-247 patients. Like hypoglycemia, it may not be clinically apparent and requires specific treatment. 1, 3

• Pregnancy test: Mandatory for all women of childbearing age, as pregnancy fundamentally alters diagnostic approach, treatment decisions, and disposition planning. 1, 2, 3

Additional Testing Based on Specific Clinical Contexts

When to Expand Laboratory Workup

The evidence strongly indicates that routine comprehensive metabolic panels have extremely low yield in patients who have returned to baseline neurologic status. 1, 5 However, expand testing in these specific scenarios:

• Complete blood count (CBC): Order when infection is suspected based on fever, altered mental status, or clinical signs of systemic illness. 2

• Calcium and magnesium: Check only in patients with known renal insufficiency, malnutrition, chronic diuretic use, known malignancy, or suspected alcohol-related seizures. The evidence shows hypocalcemia was found in only 2 of 136 patients with new-onset seizures, both of whom had known predisposing conditions (cancer and renal failure). 1, 2, 4

• Basic metabolic panel (BUN, creatinine, additional electrolytes): Reserve for patients with known renal disease, signs of dehydration, or when history suggests metabolic derangement. 2, 3

Toxicology and Drug Screening

• Drug/toxicology screen: Consider in first-time seizures when substance use is suspected, but recognize there are no prospective studies demonstrating benefit of routine screening. Alcohol withdrawal is the most common cause of acute symptomatic seizures (74.1% in one study), but this should be a diagnosis of exclusion. 1, 2, 3, 6

Critical Clinical Pitfalls to Avoid

The Low-Yield Laboratory Trap

Do not order comprehensive metabolic panels routinely. A landmark prospective study of 163 patients found that clinical examination successfully predicted laboratory abnormalities in all but 2 cases (one hyperglycemia, one subdural hematoma on imaging). Only 3 of 163 patients had significant laboratory abnormalities: 2 with hypoglycemia and 1 with hyperglycemia. 5

High-Risk Features Requiring Expanded Evaluation

Obtain more extensive laboratory testing when patients present with:

• Altered mental status that persists: Requires expanded metabolic panel, consideration of lumbar puncture after neuroimaging. 1, 3

• Fever: Mandates CBC, consideration of lumbar puncture to exclude CNS infection after head CT. 1, 3, 4

• Immunocompromised state: Requires lumbar puncture after head CT to exclude opportunistic CNS infections. 1, 2, 3, 4

• New focal neurologic deficit: Necessitates immediate neuroimaging and expanded laboratory evaluation. 1

Special Population Considerations

Older Adults (Age >40 Years)

• Maintain the same core laboratory approach (glucose, sodium, pregnancy test if applicable). 4
• Lower threshold for expanded metabolic panel given higher prevalence of comorbidities. 4
• Age >40 is an independent indication for emergent neuroimaging due to high risk of structural lesions (stroke, tumor), but does not change the core laboratory recommendations. 3, 4

Alcohol-Related Presentations

• Check magnesium level specifically in suspected alcohol withdrawal seizures, as hypomagnesemia is common in this population. 2
• Remember that alcohol withdrawal seizures should be a diagnosis of exclusion, especially in first-time presentations—always search for alternative symptomatic causes. 1, 3

What NOT to Order Routinely

There is no evidence supporting routine measurement of:

• Serum calcium, magnesium, or phosphate in otherwise healthy patients without specific risk factors. 1
• Comprehensive drug screens in all patients (reserve for those with clinical suspicion). 1
• Prolactin or creatine kinase for diagnostic purposes in the emergency setting (these may help differentiate epileptic from non-epileptic events but do not guide acute management). 7

Algorithm Summary

1. All patients: Glucose, sodium, pregnancy test (if applicable)
2. Add CBC + expanded metabolics if: fever, persistent altered mental status, known comorbidities (renal disease, malnutrition, diuretic use)
3. Add calcium/magnesium if: known malignancy, renal failure, chronic alcohol use, or on medications affecting these electrolytes
4. Consider toxicology screen if: clinical suspicion of substance use or first-time seizure in appropriate demographic
5. Lumbar puncture (after CT): if immunocompromised, fever with meningeal signs, or persistent altered mental status concerning for CNS infection

The key principle is that history and physical examination predict the vast majority of laboratory abnormalities, and only glucose and sodium have sufficient evidence for routine testing in all patients. 1, 5