A recent BMJ paper represents the largest prospective study to date aiming to differentiate a traumatic tap from true subarachnoid hemorrhage in ED patients presenting with an acute headache and a GCS of 15. But is it conclusive enough to change practice?
Aneurysmal subarachnoid hemorrhage (aSAH) is a rare disorder. Only 30,000 cases a year are reported in the United States . Of those cases, over half will have neurological symptoms or focal deficits that would prompt neuroimaging, while 40% (12,000 cases), have an isolated complaint of headache . With three million annual visits to US emergency departments for headache (the haystack) , and with only a small proportion of patients with a ‘thunderclap’ headache having an aSAH, the implication of missing the diagnosis aSAH (the needle) is readily apparent.
Past and Current Practices
In the 80s, up to 37% of patients referred to a tertiary facility for aSAH were initially misdiagnosed on their first physician visit . By the 1990s, 25% of aSAH patients treated at four neurosurgical centers were initially misdiagnosed . In a British study in the 1990s, 51% of aSAH patients were initially misdiagnosed, and 65% of those experienced rebleeding or died . The most recent estimates suggest misdiagnosis may be down to 5-12% [7,8]. In a seminal review article in 2000, Edlow and Caplan highlighted three correctable patterns that continually contribute to misdiagnosis of aSAH: “failure to appreciate the spectrum of clinical presentation, failure to understand the limitations of computed tomography (CT), and failure to perform and correctly interpret the results of lumbar puncture .” At that time, a lumbar puncture was strongly recommended by the American Heart Association in patients with a suspicion for aSAH with negative head CT .
Since the 1990s, however, the sensitivity of CT scanning has improved dramatically so the old 10mm CT slices are now replaced by modern machines with 1.25mm slices. In a Canadian prospective multicenter cohort study of 3132 patients including 240 (7.7%) with aSAH, the sensitivity of CT for diagnosing aSAH was 93% (95% confidence interval 89%-96%), the specificity was 100% (99.9%-100%), the negative predictive value was 99.4% (99.1%-99.6%), and the positive predictive value was 100% (98.3%-100%) . In 953 patients in whom CT was performed within 6 hours of headache onset, sensitivity was 100% (97%-100%), while sensitivity dropped to 86% (78%-91%) beyond six hours  However, because only one third of patients in that study had CT within six hours, we can conclude that a long delay from headache onset to ED arrival is probably common. So, lumbar puncture remains a staple and is recommended by recent guidelines  for ruling out aSAH in patients with negative head CT and clinical suspicion for aSAH.
Unfortunately, a “traumatic tap” occurs in up to 30% of lumbar punctures  prompting clinical uncertainty and additional testing in the perpetual search for the needle in the haystack. This is the context in which Perry and colleagues seek to differentiate traumatic taps from aSAH in their prospective cohort study published in the British Medical Journal in 2015 .
BMJ Study Methods
The BMJ publication was a substudy of data obtained from a prospective multicenter cohort study at 12 Canadian academic EDs from November 2000 to December 2009 used to derive the Ottawa subarachnoid hemorrhage rule . Included patients had to: be alert (defined as Glasgow coma scale (GCS) score of 15); be over 15 years old; have an “acute headache” (defined as reaching maximum intensity within an hour of onset); present to the ED within 14 days of symptom onset; and, not have recurrent headaches (defined as three or more similar headaches over six months. CTs and lumbar punctures were performed at the discretion of the treating physician.
For cerebrospinal fluid (CSF) analyses, study physicians recorded the presence of visual xanthochromia, red and white blood cell counts in the first and last tubes, and glucose and protein concentrations. Any presence of xanthochromia was considered abnormal, and increased white cell count with normal red cell counts and no xanthochromia was considered normal.
The primary outcome was aSAH. This was determined by final reports by radiologists of an aneurysm identified on neuroimaging (digital subtraction angiography or axial imaging) plus SAH on CT or xanthochromia or red cells in the final CSF tube. Non-aneurysmal SAH was not included in the primary outcome definition. Since CTs and lumbar punctures were at the discretion of the treating physician, not all enrolled patients had imaging and/or a procedure. In an attempt to capture any missed cases of aSAH, discharged patients were called at one and six months after the ED visit and a structured telephone interview and medical record review were used to assess the possibility of missed aSAH.
Of 1739 patients who underwent lumbar puncture and were included in this substudy, 641 (37%) had red blood cells (>1×106/L) in the final CSF tube or visual xanthochromia in any tube. Median time from headache onset to lumbar puncture was 17 hours.
Xanthrochromia is yellow discoloration of the CSF. After aSAH, free hemoglobin is converted to oxyhemoglobin, and after 6-12 hours is metabolized by macrophages to bilirubin. Visual differentiaion between oxyhemoglobin and bilirubin seems to be poor, but it is xanthrochomia from bilirubin that is associated with aSAH. In the UK, spectrophotometry is used to identify xanthrochromia, but in North America, visual inspection is used. There are pro and con arguments for both methods, without any clear answer about which method is better .
aSAH was identified in 15 of the 641 patients (2.3%). Seven had visual xanthochromia (32-299,365 x 106/L) and the rest had abnormal CSF red cell count (9750-600,000 x 106/L). Median red cell count in the last tube was higher in patients with aSAH (28,741 x 106/L) than in those without (20 x 106/L) (P < 0.001). The optimal cut point for aSAH was assessed with a receiver operating characteristic curve. A cut point of <2000 x 106/L had 93.3% (95% CI 66.0%-99.7%) sensitivity and 92.8% (95% CI 90.5%-94.6%) specificity for aSAH. When the absence of xanthochromia was added to red cell count <2000 x 106/L in the last tube, sensitivity was 100% (74.7%-100%) and specificity was 91.2% (88.6%-93.3%). The authors concluded that aSAH may be excluded as a cause of headache in patients who have no xanthochromia and meet this cell count cut off.
But this wasn’t enough, this very well written paper represents the largest prospective study to date aiming to differentiate a traumatic tap from true aSAH in ED patients presenting with an acute headache and a GCS of 15. The use of (mostly) visual xanthochromia plus a cut off of <2000 x 106/L red cells in the final CSF tube had acceptable test characteristics to enhance clinical decision making. The fact that only 15 cases of aSAH were diagnosed by lumbar puncture at 12 academic medical centers over a 10 year period highlights the “needle in a haystack” challenge of avoiding misdiagnosis of aSAH. The 2.3% event rate among those with abnormal CSF also results in wide 95% confidence intervals for the reported point estimate of sensitivity of 100% (74.7%-100%). The authors also cautioned that while their conclusions may be appropriate for ~90% of patients, further investigation is warranted for those with a high pretest probability.
There are many challenges for changing clinical practice based on the findings from the paper. A change in routine ED practice would entail potentially discharging patients with no xanthochromia and red cell counts <2000 x 106/L. Given the absence of data and long term follow-up in patients discharged from routine ED practice using these criteria, a change in practice is premature. The primary outcome of aSAH required the presence of an aneurysm on angiography (digital subtraction, CT or magnetic resonance) requiring neurosurgical intervention or resulting in death. As such, non-aneurysmal SAH was not included in the outcome. Clinically, it would be useful to know what proportion of patients had non-aneurysmal SAH since those patients often require additional testing to rule out an aneurysmal source. Patients with elevated white cells but normal red cells and no xanthochromia were also considered “normal” in the assessment of the primary outcome. In these cases of non-aneurysmal SAH and potential meningitis/encephalitis, hospital admission and additional testing are required, and not “unnecessary.”
Lastly, practice at academic medical centers does not reflect community practice. Even in the study’s academic settings, eight of the 15 cases identified by lumbar puncture in fact had SAH on baseline CT that was originally missed. It’s unclear from the paper if the initial interpretation of these CTs was primarily by emergency physicians or radiology residents, fellows or non-neuroradiology faculty. This emphasizes the prematurity of translating the findings of the paper to clinical practice, especially in non-academic ED settings. The authors recommend having an experienced radiologist assess CTs when feasible prior to lumbar puncture. In clinical practice, you get what you get. Just as radiologists do not get to pick their ED physician, it’s impractical for ED physicians to specify radiologists to interpret their CTs. As such, a future study of routine ED practice involving a myriad of ED practice environments is warranted prior to changing current practice.
In conclusion, this seminal report is not sufficient to solve the never-ending search for the needle in the haystack. A luta continua. Victoria ascerta.
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