What is the appropriate workup and differential diagnosis for a 47-year-old patient presenting with new onset headache?

Emergency Department Workup and Differential Diagnosis for New Onset Headache in a 47-Year-Old

For a 47-year-old presenting with new onset headache, immediately assess for life-threatening secondary causes using red flag criteria, obtain non-contrast head CT if any red flags are present, and consider subarachnoid hemorrhage as the most critical diagnosis to exclude given the patient's age and new symptom onset. 1, 2

Immediate Red Flag Assessment

The Ottawa SAH Rule must be applied first, as this patient meets criterion #1 (age ≥40 years), automatically placing them in the high-risk category requiring additional investigation 1, 2. Additional red flags to assess include:

Critical Historical Red Flags

• Thunderclap headache (sudden onset reaching maximum intensity within seconds to minutes) - suggests subarachnoid hemorrhage 1, 2
• "Worst headache of life" with abrupt onset - indicates possible vascular pathology 2
• Onset during exertion - part of Ottawa SAH criteria 1, 2
• Witnessed loss of consciousness - part of Ottawa SAH criteria 1, 2
• Progressive worsening pattern - suggests intracranial space-occupying lesion 2, 3
• Headache awakening patient from sleep - indicates possible increased intracranial pressure 2, 3
• Aggravation by Valsalva, coughing, sneezing, or exercise - suggests intracranial hypertension 2, 3
• Associated weight loss, memory changes, or personality changes - strongly suggests secondary headache 2, 3
• Atypical aura - may indicate TIA, stroke, or arteriovenous malformation 2, 3

Physical Examination Red Flags

• Neck stiffness or limited neck flexion - suggests meningitis or subarachnoid hemorrhage 1, 2
• Focal neurological symptoms or signs - indicates secondary headache requiring immediate imaging 2, 3
• Unexplained fever - suggests meningitis 2, 3
• Papilledema - indicates increased intracranial pressure 3
• Impaired memory, altered consciousness, or personality changes - suggests secondary headache 2, 3

Diagnostic Algorithm Based on Timing and Presentation

If Presenting <6 Hours from Symptom Onset WITHOUT Neurological Deficit

Obtain non-contrast head CT on a high-quality scanner interpreted by a board-certified neuroradiologist - this is sufficient to exclude subarachnoid hemorrhage with 98.7% sensitivity, missing <1.5 in 1000 cases 1. If CT is negative and clinical suspicion remains low, no further workup may be needed 1.

If Presenting >6 Hours from Symptom Onset OR WITH Neurological Deficit

Obtain non-contrast head CT followed by lumbar puncture if CT is negative - LP for xanthochromia evaluation is mandatory in this scenario as CT sensitivity decreases after 6 hours 1. This is a Class 1, Level B recommendation 1.

If SAH is Confirmed on CT

Proceed immediately to CTA to identify aneurysm source, followed by digital subtraction angiography (DSA) if CTA is negative or inconclusive, as CTA sensitivity for aneurysms <3mm is only 61% 1.

Key Differential Diagnoses by Priority

Life-Threatening (Rule Out First)

1. Subarachnoid hemorrhage - especially given age ≥40 years 1, 2
2. Bacterial meningitis - if fever and neck stiffness present 2, 3
3. Intracranial hemorrhage - if focal neurological signs 1
4. Cerebral venous thrombosis - can present with progressive headache 1
5. Giant cell arteritis - critical in patients approaching or over age 50; obtain ESR and CRP 3

Serious Secondary Causes

1. Intracranial mass/tumor - if progressive worsening, personality changes, or morning headaches 2, 3
2. Idiopathic intracranial hypertension - particularly with obesity, visual disturbances, or papilledema 3
3. Spontaneous intracranial hypotension - if orthostatic headache pattern present 1

Primary Headache Disorders (Diagnosis of Exclusion)

1. Migraine without aura - requires ≥5 attacks lasting 4-72 hours with specific characteristics 4
2. Migraine with aura - requires ≥2 attacks with reversible aura symptoms 4
3. Tension-type headache - bilateral, pressing quality, mild-moderate intensity 1, 4
4. Cluster headache - strictly unilateral, 15-180 minutes, with autonomic symptoms 1

Imaging Selection

MRI is preferred over CT for definitive evaluation when secondary causes are suspected but not emergent, as it offers higher resolution without radiation exposure 1, 2. However, non-contrast CT is the first-line test for suspected acute hemorrhage 1, 5.

Critical Pitfalls to Avoid

• Do not rely on CT alone if presentation is >6 hours from onset - LP is mandatory even with negative CT 1
• Do not dismiss atypical presentations such as primary neck pain, syncope, or seizure - these still warrant full workup 1
• Do not assume normal neurological exam excludes secondary causes - many dangerous conditions present without focal findings initially 2, 6
• Do not order MRI first if acute hemorrhage is suspected - CT is faster and more sensitive for acute blood 5
• Do not forget temporal arteritis workup in patients ≥50 years - this is a medical emergency requiring immediate ESR/CRP and consideration of empiric steroids 3

Additional Laboratory Evaluation

• ESR and CRP if age >50 or temporal arteritis suspected 3
• Complete blood count if infection suspected 6
• Metabolic panel to assess for electrolyte abnormalities 1
• Lumbar puncture with opening pressure, cell count, glucose, protein, xanthochromia if SAH suspected with negative CT 1