What is the most appropriate diagnostic test for a patient with sudden-onset severe headache, photophobia, nausea, and vomiting after physical exertion, with a normal initial computed tomography (CT) head scan?

Lumbar Puncture for Xanthochromia

Lumbar puncture with cerebrospinal fluid analysis for xanthochromia is the most appropriate next diagnostic test for this patient with suspected subarachnoid hemorrhage and a normal initial CT scan. 1, 2

Clinical Reasoning

This patient presents with classic features of subarachnoid hemorrhage (SAH):

• Sudden-onset severe "thunderclap" headache triggered by physical exertion (lifting heavy box) 1, 2
• Associated symptoms: photophobia, nausea, and vomiting 1
• First occurrence of these symptoms (critical historical feature) 1

The normal CT scan does not exclude SAH in this clinical context, particularly because:

• CT sensitivity for SAH decreases significantly after 6 hours from symptom onset 1, 2
• Even third-generation CT scans have limitations, especially in detecting small bleeds 1, 2
• This patient presented within 2 hours, but CT sensitivity is not 100% even in the hyperacute period 2, 3

Why Lumbar Puncture is Required

The Canadian Stroke Best Practice Recommendations explicitly state: When CT is performed after 6 hours, is not read by an experienced neuroradiologist, or clinical suspicion remains high despite negative CT, lumbar puncture should be performed 1. The American Heart Association similarly recommends lumbar puncture when there is high clinical suspicion with negative or non-conclusive CT 2.

Xanthochromia Detection

• Xanthochromia (yellow discoloration of CSF from bilirubin breakdown) is the key diagnostic finding, not just bloodstained CSF 4
• Spectrophotometric analysis has 100% sensitivity when performed 12 hours to 2 weeks after symptom onset 4, 5
• Visual inspection alone has lower sensitivity (83%) compared to spectrophotometry (87%) 6
• Timing is critical: Xanthochromia evaluation is most sensitive after a minimum delay of 12 hours from headache onset, though earlier testing may still be clinically appropriate 1

Clinical Outcomes Data

• In one audit, CSF xanthochromia testing had 100% sensitivity and 98.1% specificity for SAH, with 100% negative predictive value 5
• A negative xanthochromia result (when properly timed and analyzed) effectively excludes ruptured aneurysm 4
• Lumbar puncture has high diagnostic yield, eliminating need for further neurosurgical investigation in almost 90% of cases when negative 3

Why Other Options Are Inappropriate

MRI brain with SWI: While MRI sequences (FLAIR, SWI/GRE) can detect SAH, they are less sensitive than CT for acute SAH (50-94% sensitivity vs 98% for CT) and are not the recommended second-line test after negative CT 1. MRI is also time-consuming in an emergency setting 1.

CRP bloodwork: Has no role in diagnosing SAH 1, 2.

No diagnostic test: This is dangerous—SAH has >40% mortality within 30 days if untreated, with high early rebleeding risk 1. Missing this diagnosis has catastrophic consequences for morbidity and mortality 1, 2.

Critical Pitfalls to Avoid

• Do not rely on CT alone when clinical suspicion is high—CT sensitivity decreases over time and is not 100% even acutely 1, 2
• Wait at least 12 hours from symptom onset before performing LP when possible for optimal xanthochromia detection, though clinical urgency may necessitate earlier testing 1, 4
• Request spectrophotometric analysis, not just visual inspection, for maximum sensitivity 4, 6
• Beware of traumatic tap: Xanthochromia distinguishes true SAH from traumatic LP—xanthochromia takes hours to develop and indicates genuine hemorrhage 4
• Remember that bloodstained CSF without xanthochromia (when LP performed >12 hours after ictus) likely represents traumatic tap, not SAH 4