What laboratory tests are recommended for the initial workup of a headache?

Laboratory Tests for Initial Headache Workup

For the initial workup of a headache, laboratory tests are generally not indicated unless specific red flags are present that suggest a secondary headache disorder.

When Laboratory Tests Are Indicated

Laboratory testing should be performed when there are specific signs or symptoms suggesting a secondary headache disorder:

1. Suspected infection:

   • Complete blood count (CBC)
   • Erythrocyte sedimentation rate (ESR)
   • C-reactive protein (CRP)
   • Blood cultures if fever present

2. Suspected temporal arteritis (especially in patients over 50):

   • ESR
   • CRP
   • Consider temporal artery biopsy if ESR/CRP elevated 1

3. Suspected metabolic/systemic causes:

   • Basic metabolic panel
   • Liver function tests
   • Thyroid function tests

4. Suspected intracranial hypertension or hypotension:

   • Lumbar puncture with opening pressure measurement and CSF analysis 2

Red Flags That Warrant Laboratory Testing

Laboratory testing should be considered when the following red flags are present:

• Sudden severe (thunderclap) headache
• Headache with persistent vomiting
• Headache with fever or signs of infection
• New-onset headache in patients over 50 years
• Headache in immunocompromised patients
• Headache in patients with cancer history
• Headache in pregnant women with atypical features 2

Decision Algorithm for Laboratory Testing

1. Primary headache pattern with normal neurological exam and no red flags:

   • No laboratory testing needed 1, 2

2. Headache with abnormal neurological exam:

   • Neuroimaging (preferably MRI) first
   • Laboratory tests based on neuroimaging findings 1, 2

3. Headache with systemic symptoms (fever, weight loss, malaise):

   • CBC, ESR, CRP
   • Additional tests based on specific symptoms 3

4. Thunderclap headache:

   • Immediate CT or MRI
   • If imaging normal, proceed to lumbar puncture to rule out subarachnoid hemorrhage 4

Common Pitfalls to Avoid

• Overreliance on laboratory testing: Most primary headaches (migraine, tension-type) can be diagnosed based on history and examination alone 1, 5

• Failure to recognize temporal arteritis: In patients over 50 with new-onset headache, always consider temporal arteritis and check ESR/CRP, as missing this diagnosis can lead to blindness 6

• Misdiagnosing "sinus headache": Approximately 62% of migraineurs have cranial autonomic symptoms that can mimic sinusitis; unnecessary sinus imaging and testing should be avoided 2

• Neglecting lumbar puncture after negative imaging: When thunderclap headache is present, a normal CT/MRI does not rule out subarachnoid hemorrhage; lumbar puncture is still indicated 4

Laboratory testing should be targeted based on clinical suspicion rather than performed as a routine battery of tests. The yield of extensive laboratory testing in patients with typical features of primary headache disorders and normal neurological examinations is extremely low 5.

Emerging Laboratory Tests

While not yet part of routine clinical practice, research is exploring several promising laboratory tests for headache diagnosis:

• Palpometer testing and quantitative sensory testing for migraine and tension-type headache
• Nociceptive blink reflex and autonomic tests for trigeminal autonomic cephalalgias
• Provocation tests with glyceryl trinitrate (GTN) and calcitonin gene-related peptide (CGRP) 7

These tests remain primarily research tools and are not currently recommended for routine clinical use.