Abstract
Background and Purpose
Patients suspected of having aneurysmal subarachnoid hemorrhage (SAH) are initially evaluated with noncontrast head computed tomography (CT). If the CT is negative, but clinical concern for SAH is high, a lumbar puncture (LP) with cerebrospinal fluid (CSF) analysis is typically performed. The purpose of this study was to evaluate the accuracy of CSF xanthochromia and erythrocytosis for aneurysmal SAH.
Methods
Medical records of all patients who underwent catheter angiography at Barnes Jewish Hospital between July 2002 and April 2012 for clinical suspicion of a ruptured brain aneurysm after a negative CT scan and an LP suspicious for SAH were reviewed. The CSF analysis results, angiographic findings and outcomes of each case were recorded.
Results
Fifty nine patients were identified. Two angiographic lesions were identified in patients with xanthochromia was 8.3% (2/24), both of which were confirmed to have ruptured. The diagnostic yield in patients with non-clearing erythrocytosis and no xanthrochromia was 6.3% (1/16), though this lesion was not considered the source of SAH.
Conclusion
Catheter angiography should be performed in patients with CT negative but suspicious LP, particularly in the presence of xanthrochromia. The benefit of angiography in patients with erythrocytosis only is unclear and deserves future study.
Keywords: Angiography, aneurysm, computed tomography, lumbar puncture, subarachnoid hemorrhage
Introduction
Computed tomography (CT) is 93% sensitive for subarachnoid hemorrhage (SAH) within the first 24 hours, but falls to 50% after one week due to resorption of subarachnoid blood 1. Because catheter angiography often identifies incidental aneurysms which may not require treatment lumbar puncture (LP) for cerebrospinal fluid (CSF) analysis 2 is typically performed. The purpose of this study was to evaluate the accuracy of CSF xanthochromia and erythrocytosis for aneurysmal SAH.
Methods
Institutional review board approval was obtained to retrospectively review the medical records of all patients who underwent catheter angiography at Barnes Jewish Hospital between July 2002 and April 2012. Patients included in the study had a negative noncontrast head CT at initial assessment at our institution, but an LP suspicious for SAH based on the presence of CSF erythrocytosis or visual xanthochromia. Cerebrospinal fluid samples were centrifuged at 11,000 rpm for 5 minutes and visually inspected for xanthochromia. Non-clearing erythrocytosis was defined as a cell count that decreased less than 25% over three to four serial samples of XX mL. Dictated reports of catheter angiography were reviewed. The images for patients identified with brain aneurysms were reviewed, as well as their hospital course. We attempted to determine whether the aneurysm was responsible for SAH or an incidental finding based on observation at surgery (if operated) or clinical course. The diagnostic yield was calculated for the entire cohort. Subgroups of patients were defined by CSF analysis results and the diagnostic yield for each was calculated
Results
Our cohort included 57 patients. The duration between symptom onset and CT scanning could be retrospectively determined for 46 patients (81%; 46/57). Of these patients, 35% (20/57) were scanned within 24 hours, 49% (28/57) were scanned within 3 days, and 8.8% (5/57) were scanned more than one week after ictus.
Xanthochromia was visualized in 42% (24/57) of cases. Patients with CSF samples that were negative (24/57; 42%) or not inspected for xanthochromia (11/57; 19%) went to catheter angiography based on the presence of CSF erythrocytosis. Table 1 summarizes CSF erythrocytosis results. Serial sampling was performed in 44 patients (77%; 44/57). Non-clearing erythrocytosis was observed in 89% (16/18) of serial samples that were negative for xanthochromia.
Table 1.
Summary of CSF erythrocyte counts.
| Maximum Cell Count (cells/mm3) | Serial Sampling | ||||||||
|---|---|---|---|---|---|---|---|---|---|
|
|
|||||||||
| Patients | < 1k | 1-5k | 5-10k | >10k | Obtained | Cell Count Increased > 25% | Cell Count Changed <25% | Cell Count Decreased >25% | |
| Total | 59 | 14 (24%) | 17 (29%) | 3 (5.1%) | 25 (42%) | 44 (76%) | 16 (36%) | 13 (30%) | 15 (34%) |
| Xanthochromia + | 24 (41%) | 3 (13%) | 7 (29%) | 2 (8.3%) | 12 (50%) | 17 (71%) | 3 (18%) | 4 (24%) | 10 (59%) |
| Xanthochromia – | 24 (41%) | 7 (29%) | 5 (21%) | 1 (4.1%) | 11 (46%) | 18 (75%) | 9 (50%) | 7 (39%) | 2 (11%) |
| Xanthochromia Not Evaluated | 11 (18%) | 4 (36%) | 5 (45%) | 0 (0%) | 2 (18%) | 9 (82%) | 4 (44%) | 2 (22%) | 3 (33%) |
Angiography identified three lesions (5.3%; 3/57) (Table 2). The diagnostic yield in patients with xanthochromia was 8.3% (2/24). Considering only the subgroup of patients with positive xanthochromia where serial samples were obtained and non-clearing erythrocytosis was present, the diagnostic yield was 29% (2/7). One patient had a vertebral artery dissection that progressed to a pseudoaneurysm prompting vertebral artery coil embolization. The second patient had a 2 mm carotid bifurcation aneurysm that was successfully treated with surgical clipping. Yellow-tinged subarachnoid fluid was noted during surgery consistent with SAH. The interval between symptom onset and clinical evaluation was 5 days for both these patients.
Table 2.
Clinical features and CSF analysis results of patients with positive angiograms.
| Serial Sampling Erythrocyte Cell Count | |||||||
|---|---|---|---|---|---|---|---|
|
| |||||||
| Patient | Time to Presentation | Xanthochromia | First Tube | Last Tube | Δ | Angiography | Rupture Confirmed? |
| 37/M | 5 days | + | 1,118 | 3,268 | + 192% | Distal VA dissection. | Y |
| 23/W | < 24 hours | - | 27 | 163 | +504% | 1.5 mm Acomm aneurysm | N |
| 51/W | 5 days | + | 13,378 | 13,289 | - 0.67% | 2 mm ICA bifurcation aneurysm | Y |
CSF, cerebrospinal fluid; VA, vertebral artery; Acomm, anterior communicating artery; ICA, internal carotid artery.
Considering only the subgroup of patients with negative xanthochromia where serial samples were obtained and non-clearing erythrocytosis was present, the diagnostic yield was 6.3% (1/16). This patient was found to have a 1.5 mm anterior communicating artery aneurysm, which was left untreated and remained stable over a 1 year angiographic and 5.5 year clinical follow-up period.
Discussion
Xanthochromia is produced by hemolysis of subarachnoid erythrocytes which releases oxyhemoglobin that is gradually converted into bilirubin by macrophages and other cells in the leptomeninges (Ref:Vindlacheruvu). Xanthochromia becomes apparent approximately 12 hours after SAH and persists for at least two weeks 12. Aneurysms were identified in 8.3% (2/22) patients with xanthochromia, both of which were proven to have ruptured. These findings suggest that CSF xanthochromia warrants further evaluation with catheter angiography to exclude a ruptured aneurysm.
Many institutions use non-clearing erythrocytosis in addition to or instead of xanthochromia to determine whether further evaluation for a ruptured aneurysm is necessary. Considering only the subgroup of patients with positive xanthochromia where serial samples were obtained and non-clearing erythrocytosis was present, the diagnostic yield was 29% (2/7). These findings suggest that patients with xanthrochromia and non-clearing erythrocytosis are at greatest risk for having a ruptured aneurysm. Within our subgroup of 16 patients with negative xanthochromia where serial samples were obtained and non-clearing erythrocytosis was present, one aneurysm (6.2%) was identified which was most likely incidental. Thus, the value of angiography in these patients may be limited.
Only one other study has addressed the prevalence of angiographic lesions in patients with negative CT, but positive LP for SAH. Horstman et al. reported an overall diagnostic yield of 53% (16/30) 7. The lower yield in our study likely reflects multiple factors. First, 59% (35/59) of our patients were diagnosed with SAH based on the presence of CSF erythrocytosis alone. In contrast, Horstman's cohort only included patients with CSF xanthochromia. Second, while xanthochromia was identified visually in our study, Horstman et al. identified xanthochromia using spectrophotometry. Spectrophotometry is more specific for SAH because it can differentiate between in vivo blood degradation products and in vitro lysis of erythrocytes following a traumatic tap 9, but is unavailable in the United States. Finally, 93% (28/30) of Horstman's cohort presented more than 3 days after ictus compared to 51% (29/57) of patients in our study. Both of our patients with proven aneurysms presented five days after the onset of symptoms.
There are several limitations of this study. This study is small and retrospective. Data collection regarding presence of xanthrochromia is incomplete. This analysis was limited to imaging and laboratory aspects of presentation. Patients with severe neurological injury and a poor prognosis or large parenchymal hematomas and acute neurological decline may not undergo catheter angiography, thus introducing selection bias into the data. However, neither of these groups of patients is likely to be CT negative.
Conclusion
Catheter angiography should be performed in patients with CT negative but suspicious LP, particularly in the presence of xanthrochromia. The benefit of angiography in patients with erythrocytosis only is unclear and deserves future study.
Figure 1A.
Dissecting vertebral artery aneurysm in a patient with xanthochromia. B. Carotid bifurcation aneurysm in a second patient with visual xanthochromia. C. Anterior communicating artery aneurysm in a patient with negative xanthochromia and non-clearing erythrocytosis.
Imaging of the brain and arteries: angiography
Diagnostic testing: CT and MRI
Acknowledgments
Funding, Conflicts: None.
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