Which labs are indicated for a patient with severe migraines, persistent headache, and neuropathic pain?

Laboratory Testing for Severe Migraines and Headache

Routine laboratory testing is not indicated for patients with migraine, severe headache, or neuropathic pain who have a normal neurological examination. 1, 2

When Laboratory Testing is NOT Needed

The diagnosis of migraine is clinical and does not require laboratory confirmation. 1, 3 The most important determinant of whether any testing is warranted is the neurological examination—when normal, the probability of clinically significant pathology is approximately 0.2%, equivalent to the general asymptomatic population. 2, 3

Laboratory work-up should be avoided if it will not lead to a change in management. 1, 2

Red Flags That Warrant Investigation

Laboratory testing should be considered only when specific red flags are present in the history or physical examination: 1, 3

• Unexplained fever with headache (concern for meningitis or infection) 1, 3
• New-onset headache after age 50 (concern for giant cell arteritis) 1, 3, 4
• Focal neurological symptoms or abnormal neurological examination 1, 2
• Thunderclap headache ("worst headache of life") 1, 3, 4
• Progressive worsening over weeks 2, 3
• Headache awakening patient from sleep 1, 3, 4

Specific Laboratory Tests Based on Clinical Suspicion

For Suspected Giant Cell Arteritis (Age >50 with new headache)

• ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) are indicated when temporal arteritis is suspected, though ESR can be normal in 10-36% of cases. 3
• Scalp tenderness or jaw claudication increases suspicion. 3

For Suspected Metabolic or Endocrine Causes

• Morning TSH and free T4 if cold intolerance or lightheadedness is present (hypothyroidism). 3
• Thyroid peroxidase (TPO) antibodies if biochemical hypothyroidism is confirmed. 3
• Serum calcium and phosphate only if there is specific clinical suspicion for metabolic disorder (e.g., incidental basal ganglia calcifications on imaging). 2

For Suspected Infection

• Blood cultures, complete blood count, and inflammatory markers if meningitis or systemic infection is suspected based on fever and neck stiffness. 3

What NOT to Order

Do not order "routine labs" such as CBC, CMP, or metabolic panels in patients with typical migraine features and normal neurological examination. 1, 2 While research has identified metabolic profiles and biomarkers in migraine patients 5, 6, these are not clinically validated for diagnosis or management and should not be ordered in routine practice.

The Diagnostic Approach

The diagnosis of migraine relies on: 1, 3

• Detailed headache history including frequency, duration, location, quality, associated symptoms (nausea, photophobia, phonophobia)
• Headache diary to document pattern and medication use 1
• Screening questionnaires such as ID-Migraine (sensitivity 0.81, specificity 0.75) or Migraine Screen Questionnaire (sensitivity 0.93, specificity 0.81) 1, 3
• Thorough neurological examination 2, 3

Common Pitfalls to Avoid

• Ordering labs "just to be safe" in patients with classic migraine and normal exam—this does not improve outcomes and increases costs. 1, 2
• Assuming neuropathic pain requires different lab work-up—the same principles apply; testing is guided by red flags, not pain type. 3, 7
• Conflating the need for neuroimaging with laboratory testing—neuroimaging may be indicated when labs are not, and vice versa. 1, 2