Diffuse Angiogram-Negative Subarachnoid Hemorrhage is Associated with an Intermediate Clinical Course

Background: The cerebral angiography result is negative for an underlying vascular lesion in 15-20% of patients with nontraumatic subarachnoid hemorrhage (SAH). Patients with angiogram-negative SAH include those with perimesencephalic SAH and diffuse SAH. Consensus suggests that perimesencephalic SAH confers a more favorable prognosis than diffuse SAH. Limited data exist to contextualize the clinical course and prognosis of diffuse SAH in relation to aneurysmal SAH in terms of critical care complications, neurologic complications, and functional outcomes. Here we compare the clinical course and functional outcomes of patients with perimesencephalic SAH, diffuse SAH, and aneurysmal SAH to better characterize the prognostic implications of each SAH subtype. Methods: We conducted a retrospective cohort study that included all patients with nontraumatic SAH admitted to a tertiary care referral center between January 1, 2012, and December 31, 2017. Bleed patterns were radiographically adjudicated, and patients were assigned to three groups: perimesencephalic SAH, diffuse SAH, and aneurysmal SAH. Patient demographics, complications, and clinical outcomes were reported and compared. Results: Eighty-six patients with perimesencephalic SAH, 174 with diffuse SAH, and 998 with aneurysmal SAH presented during the study period. Patients with aneurysmal SAH were significantly more likely to be female, White, and active smokers. There were no significant differences between patients with diffuse SAH and perimesencephalic SAH patterns. Critical care complications were compared across all three groups, with significant between-group differences in hypotension and shock (3.5% vs. 16.1% vs. 38.4% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01) and endotracheal intubation (0% vs. 26.4% vs. 48.8% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.01). Similar trends were noted with long-term supportive care with tracheostomy and gastrostomy tubes and length of stay. Cerebrospinal fluid diversion was increasingly required across bleed types (9.3% vs. 54.6% vs. 76.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively, p < 0.001). Vasospasm and delayed cerebral ischemia were comparable between perimesencephalic SAH and diffuse SAH but significantly lower than aneurysmal SAH. Patients with diffuse SAH had intermediate functional outcomes, with significant rates of nonhome discharge (23.0%) and poor functional status on discharge (26.4%), significantly higher than patients with perimesencephalic SAH and lower than patients with aneurysmal SAH. Diffuse SAH similarly conferred an intermediate rate of good functional outcomes at 1-6 months post discharge (92.3% vs. 78.6% vs. 47.3% for perimesencephalic SAH vs. diffuse SAH vs. aneurysmal SAH, respectively; p < 0.016). Conclusions: We confirm the consensus data that perimesencephalic SAH is associated with a more benign clinical course but demonstrate that diffuse SAH confers an intermediate prognosis, more malignant than perimesencephalic SAH but not as morbid as aneurysmal SAH. These results highlight the significant morbidity associated with diffuse SAH and emphasize need for vigilance in the acute care of these patients. These patients will likely benefit from continued high-acuity observation and potential support to avert significant risk of morbidity and neurologic compromise.