In a patient >6 hours after onset of acute severe headache with a negative non‑contrast head CT, should I obtain a CT angiography or perform a lumbar puncture to rule out subarachnoid hemorrhage?

Ruling Out Subarachnoid Hemorrhage After 6 Hours: LP vs CTA

Perform a lumbar puncture (LP) with spectrophotometric analysis for xanthochromia in patients presenting >6 hours after headache onset with a negative non-contrast head CT and high clinical suspicion for SAH. CTA should not be used as an alternative to LP in this scenario because it only evaluates cerebrovascular anatomy, not the presence of blood in the subarachnoid space 1.

Why LP is the Correct Next Step After 6 Hours

The fundamental issue is that CTA and LP answer different diagnostic questions. CTA detects aneurysms and vascular abnormalities with approximately 97.2% sensitivity overall, but drops to only 61% sensitivity for aneurysms <3 mm 1. More critically, **CTA does not directly evaluate for SAH itself—it only identifies potential bleeding sources** 1. In contrast, LP with spectrophotometric xanthochromia analysis has 100% sensitivity and 95.2% specificity for detecting SAH when performed >6 hours after symptom onset 1.

The 6-Hour Threshold Matters

• Within 6 hours: A negative high-quality CT scan interpreted by a fellowship-trained neuroradiologist is sufficient to exclude SAH, with sensitivity of 98.7-99.9%, missing fewer than 1.5 in 1000 cases 1, 2
• Beyond 6 hours: CT sensitivity declines significantly (93% at 24 hours, 57-85% at 6 days), making LP mandatory if clinical suspicion remains high 1, 2, 3

The 2023 American Heart Association/American Stroke Association guidelines explicitly state: "LP for xanthochromia evaluation should be performed in patients presenting >6 hours from ictus in whom there is high suspicion for SAH" 1.

Proper LP Technique and Timing

• Wait at least 6-12 hours after symptom onset before performing LP to allow xanthochromia to develop, though xanthochromia may be more sensitive after 12 hours 1, 3
• Spectrophotometric analysis is mandatory—visual inspection alone is insufficient 4, 3
• CSF analysis must include cell count with differential, xanthochromia testing, protein, and glucose 3

When CTA Becomes Relevant

CTA is the appropriate next step after SAH has been confirmed on either CT or LP, not as a replacement for LP in ruling out SAH 4, 2. Once blood is detected:

• CTA provides rapid, non-invasive aneurysm detection with >90% sensitivity for most aneurysms 4, 2
• Digital subtraction angiography (DSA) remains the gold standard with >98% sensitivity and is required for small aneurysms or when CTA is negative but diffuse SAH pattern is present 1, 4, 3

Clinical Decision Framework

The 2015 Canadian Stroke Best Practice guidelines provide clear algorithmic guidance 1:

1. Third-generation or higher CT within 6 hours + neuroradiologist interpretation = negative: LP not required 1, 2
2. CT performed >6 hours after onset: LP required regardless of CT result 1, 2, 3
3. No experienced neuroradiologist available: LP required even if CT is within 6 hours 1
4. Lower generation CT scanner used: LP required 1
5. Patient in altered consciousness: LP required 1

Critical Pitfalls to Avoid

• Never skip LP after negative CT >6 hours from onset—this is the most common diagnostic error, as CT sensitivity declines significantly after this window 4, 2, 3
• Do not use CTA as a substitute for LP when ruling out SAH—no study has validated this approach, and the American College of Emergency Physicians provides only Level C evidence for CTA as an alternative, specifically noting it does not directly evaluate for SAH 1
• Do not dismiss severe headache based solely on negative CT when clinical suspicion remains high—misdiagnosis increases mortality four-fold 3
• Recent systematic review data (2025) confirms that if LP were removed from the diagnostic pathway for negative CT >6 hours, approximately 24 SAH cases per year would be missed in the UK alone (95% CI 0-278) 5

The Evidence Gap

No study has directly compared CTA versus LP as the next diagnostic step in patients with high suspicion for SAH and a normal head CT 1. Given the severe morbidity and potential mortality of missed SAH, and the fact that CTA and LP evaluate fundamentally different aspects of the disease (vascular anatomy vs. presence of blood), the guideline consensus strongly favors LP for ruling out SAH after 6 hours 1, 4.