What is the appropriate work‑up for a patient presenting with a headache?

Headache Work-Up: A Structured Approach

Begin by immediately assessing for red-flag features that mandate urgent neuroimaging or emergency referral, as these indicate potentially life-threatening conditions requiring immediate intervention. 1

Red-Flag Assessment (Immediate Evaluation Required)

Perform a focused history and neurological examination specifically targeting these critical features:

• Thunderclap headache (maximal intensity within seconds) – indicates possible subarachnoid hemorrhage requiring non-contrast CT within 6 hours (sensitivity 95% on day 0, falling to 74% by day 3) 1, 2
• New-onset headache after age 50 – carries approximately 12-fold higher risk of serious intracranial pathology 1
• Headache awakening patient from sleep – suggests increased intracranial pressure from mass lesion 1, 3
• Progressive worsening over weeks to months – concerning for tumor or subdural hematoma 1
• Headache triggered by Valsalva, coughing, or exertion – may indicate increased intracranial pressure 1
• Focal neurological deficits on examination – suggests structural lesion 1
• Neck stiffness with unexplained fever – meningitis until proven otherwise, requires immediate evaluation 1
• Altered consciousness, memory, or personality changes – indicates serious intracranial pathology 1
• Recent head or neck trauma – risk of subdural hematoma or arterial dissection 1
• Atypical aura lasting >60 minutes or with focal neurological symptoms – may represent stroke or TIA 1

Critical Physical Examination Elements

• Fundoscopic examination is mandatory to detect papilledema indicating increased intracranial pressure 3, 4
• Complete neurological examination including cranial nerves, motor/sensory testing, cerebellar function, gait, and mental status 3
• Vital signs with blood pressure measurement 3
• Pupil examination for size, shape, reactivity, and relative afferent pupillary defect 4

Neuroimaging Algorithm

If ANY red flag is present or neurological examination is abnormal, neuroimaging is mandatory: 1, 3

• Non-contrast CT head – first-line only for suspected subarachnoid hemorrhage presenting within 6 hours, or acute trauma 1
• MRI brain with and without gadolinium contrast – preferred modality for all other scenarios; superior sensitivity for tumors, stroke, inflammatory processes, and parenchymal abnormalities 1, 3, 4
• CT head without contrast – acceptable substitute only if MRI unavailable or contraindicated, but less sensitive 4

If initial CT is negative for subarachnoid hemorrhage but clinical suspicion remains high, perform lumbar puncture with spectrophotometric analysis for xanthochromia (100% sensitive from 12 hours to 2 weeks post-bleed). 1

Laboratory Testing (When Indicated)

• ESR and CRP – mandatory if patient >50 years with new-onset headache to exclude giant cell arteritis (note: ESR normal in 10-36% of cases) 1, 4
• Morning TSH and free T4 – if cold intolerance or lightheadedness present 1
• Complete blood count and basic metabolic panel – in patients with systemic symptoms 4

Primary Headache Diagnosis (After Excluding Red Flags)

Migraine Without Aura Criteria

Requires all of the following 1:

• ≥5 lifetime attacks lasting 4-72 hours (2-72 hours in children <18 years) 1
• ≥2 pain characteristics: unilateral location, pulsating quality, moderate-to-severe intensity, or aggravation by routine activity 1
• ≥1 associated symptom: nausea/vomiting OR both photophobia and phonophobia 1

The combined presence of photophobia with nausea strongly supports migraine diagnosis. 1

Tension-Type Headache Criteria

• Bilateral, pressing/tightening pain of mild-to-moderate intensity 1
• Not aggravated by routine physical activity 1
• Lacks nausea/vomiting and the combination of photophobia plus phonophobia 1
• Duration: 30 minutes to 7 days (highly variable) 1

Cluster Headache Criteria

• Strictly unilateral severe pain lasting 15-180 minutes 1
• Ipsilateral autonomic symptoms: lacrimation, conjunctival injection, nasal congestion, ptosis, miosis, eyelid edema 1
• Frequency: 1-8 attacks daily during cluster periods 1
• Prevalence: approximately 0.1% of population 1

Chronic Migraine

• ≥15 headache days per month for >3 months 1
• ≥8 days per month meeting migraine criteria 1
• Requires preventive therapy and neurology referral 1

Medication-Overuse Headache

• ≥15 headache days per month with regular overuse of: 1
  • Non-opioid analgesics ≥15 days/month, OR
  • Other acute medications ≥10 days/month
• Duration: >3 months 1

Diagnostic Tools for Primary Headache

• ID-Migraine questionnaire (3-item): sensitivity 0.81, specificity 0.75, positive predictive value 0.93 1
• Headache diary: document frequency, duration, character, triggers, accompanying symptoms, medication use – reduces recall bias and increases diagnostic accuracy 1

When Neuroimaging Is NOT Indicated

Neuroimaging is not routinely indicated for patients with typical migraine features and completely normal neurological examination, even after failed first-line treatments. 1 The yield in this population is 0.2% (2/1086), no higher than the 0.4% rate in asymptomatic volunteers 1.

Referral Pathways

• Emergency admission: any red flag present, patient unable to self-care without help 1
• Urgent neurology referral (within 48 hours): suspected spontaneous intracranial hypotension 1
• Urgent ophthalmology referral: papilledema identified, suspected acute angle-closure glaucoma, uveitis 4
• Routine neurology referral (2-4 weeks): suspected primary headache disorder, diagnosis uncertain, first-line treatments fail 1
• Rheumatology referral: suspected giant cell arteritis 1

Common Pitfalls to Avoid

• Do not skip fundoscopic examination – essential for detecting papilledema and increased intracranial pressure 3
• Do not dismiss sleep-disrupting headaches – this pattern specifically suggests increased intracranial pressure 3
• Do not order CT when MRI is available for non-emergent evaluation – MRI is superior for detecting mass lesions 3, 4
• Do not assume patients report all medications – many do not consider over-the-counter analgesics as "real" medications, leading to under-recognition of medication-overuse headache 1
• Do not order neuroimaging for typical migraine with normal exam – adds cost without influencing management 1