Why does the CT scan show no evidence of hemorrhage in a patient with seizure, headache, stiff neck, and non-responsiveness, with cerebrospinal fluid (CSF) analysis showing elevated red blood cells (RBC), protein, and white blood cells (WBC), and yellow discoloration?

CT-Negative Subarachnoid Hemorrhage with Elevated CSF Parameters

The patient's clinical presentation and CSF findings strongly suggest subarachnoid hemorrhage (SAH) despite a negative CT scan, which can occur in up to 15% of SAH cases, particularly in anemic patients or when imaging is performed after the first 24 hours of symptom onset. 1, 2

Clinical Presentation Analysis

The patient presents with classic signs of SAH:

• Seizure
• Headache preceding seizure (possible sentinel headache)
• Stiff neck (nuchal rigidity)
• Non-responsiveness
• CSF with yellow discoloration (xanthochromia)
• Elevated CSF protein, RBCs, and WBCs

Why CT May Be Negative Despite SAH

1. Timing of CT scan:

   • CT sensitivity decreases significantly with time:
     • 98-100% sensitive within first 12 hours
     • 93% sensitive at 24 hours
     • Only 57-85% sensitive by day 6 1, 3

2. Blood volume and distribution:

   • Small-volume hemorrhages may be below CT detection threshold
   • Blood may have already begun to clear from subarachnoid space

3. Patient factors:

   • Anemia can significantly reduce CT sensitivity for SAH 2
   • Hydration status affects blood density on imaging

4. Technical factors:

   • CT scanner generation/quality
   • Slice thickness
   • Radiologist experience 3

CSF Findings Interpretation

The CSF findings strongly support SAH diagnosis:

• Xanthochromia: Yellow discoloration of CSF is highly specific for SAH when present after 12 hours from symptom onset 1, 3
• Elevated RBCs: Consistent with blood in subarachnoid space 4
• Elevated protein: Common in SAH due to blood breakdown products 4
• Elevated WBCs: Inflammatory response to blood in subarachnoid space

Diagnostic Algorithm for Suspected SAH

1. Initial presentation with thunderclap headache, seizure, or altered mental status:

   • Immediate non-contrast head CT

2. If CT is negative but clinical suspicion remains high:

   • Proceed to lumbar puncture (LP) for CSF analysis
   • Look for xanthochromia, RBC count, protein levels

3. If LP shows xanthochromia and/or elevated RBCs:

   • Proceed to vascular imaging (CTA or DSA)
   • DSA with 3D rotational angiography is the gold standard 1

4. If initial vascular imaging is negative:

   • Consider repeat DSA in 1-2 weeks (to detect initially undetectable aneurysms)
   • Consider MRI with FLAIR sequences which may detect SAH missed on CT 1, 3

Clinical Pitfalls to Avoid

1. Misinterpreting xanthochromia:

   • While traumatic LP can cause xanthochromia in samples with >10,000 RBCs/μL within 2 hours, true SAH typically shows xanthochromia with proportionally lower RBC counts 5
   • Other causes of xanthochromia include hyperbilirubinemia, elevated CSF protein, and certain viral infections 6

2. Relying solely on CT:

   • Even modern CT scanners can miss SAH, particularly in anemic patients 2
   • The Ottawa SAH Rule helps identify patients requiring further workup 1

3. Dismissing sentinel headaches:

   • 10-43% of SAH patients report warning headaches before major rupture
   • Sentinel headaches increase rebleeding risk 10-fold 1

4. Delaying treatment:

   • Rebleeding risk is highest in first 24 hours (particularly first 6 hours)
   • Early aneurysm treatment significantly reduces mortality 1

Management Recommendations

Given the clinical presentation and CSF findings:

1. Immediate vascular imaging:

   • CTA initially, followed by DSA if CTA is inconclusive 1
   • Search for aneurysm or other vascular malformation

2. Blood pressure management:

   • Control acute hypertension to reduce rebleeding risk
   • Use titratable medications (nicardipine preferred over labetalol) 1

3. Neurosurgical/neurointerventional consultation:

   • Early treatment of identified aneurysms reduces rebleeding risk
   • Treatment within 72 hours is associated with better outcomes 1

4. Seizure management:

   • Treat seizures appropriately as they occur in up to 20% of SAH patients 1

This patient's presentation represents a classic but challenging diagnostic scenario that highlights the importance of CSF analysis when clinical suspicion for SAH remains high despite negative CT imaging.