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

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Abstract

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.

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References

  1. Kassell NF, Torner JC, Jane JA, Haley EC Jr, Adams HP. The international cooperative study on the timing of aneurysm surgery. Part 2: surgical results. J Neurosurg. 1990;73:37–47.

    Article  CAS  Google Scholar 

  2. Rinkel GJ, van Gijn J, Wijdicks EF. Subarachnoid hemorrhage without detectable aneurysm. A review of the causes. Stroke. 1993;24:1403–9.

    Article  CAS  Google Scholar 

  3. Elhadi AM, Zabramski JM, Almefty KK, et al. Spontaneous subarachnoid hemorrhage of unknown origin: hospital course and long-term clinical and angiographic follow-up. J Neurosurg. 2015;122:663–70.

    Article  Google Scholar 

  4. Rinkel GJ, Wijdicks EF, Vermeulen M, Hasan D, Brouwers PJ, van Gijn J. The clinical course of perimesencephalic nonaneurysmal subarachnoid hemorrhage. Ann Neurol. 1991;29:463–8.

    Article  CAS  Google Scholar 

  5. van Gijn J, van Dongen KJ, Vermeulen M, Hijdra A. Perimesencephalic hemorrhage: a nonaneurysmal and benign form of subarachnoid hemorrhage. Neurology. 1985;35:493–7.

    Article  Google Scholar 

  6. Nesvick CL, Oushy S, Rinaldo L, Wijdicks EF, Lanzino G, Rabinstein AA. Clinical complications and outcomes of angiographically negative subarachnoid hemorrhage. Neurology. 2019;92:e2385–94.

    Article  Google Scholar 

  7. Mensing LA, Vergouwen MDI, Laban KG, et al. Perimesencephalic hemorrhage: a review of epidemiology, risk factors, presumed cause, clinical course, and outcome. Stroke. 2018;49:1363–70.

    Article  Google Scholar 

  8. Akcakaya MO, Aydoseli A, Aras Y, et al. Clinical course of non-traumatic non-aneurysmal subarachnoid hemorrhage: a single institution experience over 10 years and review of the contemporary literature. Turk Neurosurg. 2017;27:732–42.

    PubMed  Google Scholar 

  9. Al-Mufti F, Merkler AE, Boehme AK, et al. Functional outcomes and delayed cerebral ischemia following nonperimesencephalic angiogram-negative subarachnoid hemorrhage similar to aneurysmal subarachnoid hemorrhage. Neurosurgery. 2018;82:359–64.

    Article  Google Scholar 

  10. Hui FK, Tumialan LM, Tanaka T, Cawley CM, Zhang YJ. Clinical differences between angiographically negative, diffuse subarachnoid hemorrhage and perimesencephalic subarachnoid hemorrhage. Neurocrit Care. 2009;11:64–70.

    Article  Google Scholar 

  11. Lin N, Zenonos G, Kim AH, et al. Angiogram-negative subarachnoid hemorrhage: relationship between bleeding pattern and clinical outcome. Neurocrit Care. 2012;16:389–98.

    Article  Google Scholar 

  12. Walcott BP, Stapleton CJ, Koch MJ, Ogilvy CS. Diffuse patterns of nonaneurysmal subarachnoid hemorrhage originating from the Basal cisterns have predictable vasospasm rates similar to aneurysmal subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2015;24:795–801.

    Article  Google Scholar 

  13. Samuels OB, Sadan O, Feng C, et al. Aneurysmal subarachnoid hemorrhage: trends, outcomes, and predictions from a 15-year perspective of a single neurocritical care unit. Neurosurgery. 2021;88:574–83.

    Article  Google Scholar 

  14. Rinkel GJ, Wijdicks EF, Hasan D, et al. Outcome in patients with subarachnoid haemorrhage and negative angiography according to pattern of haemorrhage on computed tomography. Lancet. 1991;338:964–8.

    Article  CAS  Google Scholar 

  15. Frontera JA, Claassen J, Schmidt JM, et al. Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale. Neurosurgery. 2006;59:21–7 (discussion-7).

    Article  Google Scholar 

  16. Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41:2391–5.

    Article  Google Scholar 

  17. Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg. 1968;28:14–20.

    Article  CAS  Google Scholar 

  18. Catapano JS, Lang MJ, Koester SW, et al. Digital subtraction cerebral angiography after negative computed tomography angiography findings in non-traumatic subarachnoid hemorrhage. J Neurointerv Surg. 2020;12:526–30.

    Article  Google Scholar 

  19. Diringer MN, Bleck TP, Claude Hemphill J, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.

    Article  Google Scholar 

  20. Ray WZ, Strom RG, Blackburn SL, Ashley WW, Sicard GA, Rich KM. Incidence of deep venous thrombosis after subarachnoid hemorrhage. J Neurosurg. 2009;110:1010–4.

    Article  Google Scholar 

  21. Kshettry VR, Rosenbaum BP, Seicean A, Kelly ML, Schiltz NK, Weil RJ. Incidence and risk factors associated with in-hospital venous thromboembolism after aneurysmal subarachnoid hemorrhage. J Clin Neurosci. 2014;21:282–6.

    Article  Google Scholar 

  22. Stein PD, Beemath A, Olson RE. Trends in the incidence of pulmonary embolism and deep venous thrombosis in hospitalized patients. Am J Cardiol. 2005;95:1525–6.

    Article  Google Scholar 

  23. Liu V, Kipnis P, Rizk NW, Escobar GJ. Adverse outcomes associated with delayed intensive care unit transfers in an integrated healthcare system. J Hosp Med. 2012;7:224–30.

    Article  Google Scholar 

  24. Escobar GJ, Greene JD, Gardner MN, Marelich GP, Quick B, Kipnis P. Intra-hospital transfers to a higher level of care: contribution to total hospital and intensive care unit (ICU) mortality and length of stay (LOS). J Hosp Med. 2011;6:74–80.

    Article  Google Scholar 

  25. Macdonald RL, Jaja B, Cusimano MD, et al. SAHIT Investigators–on the outcome of some subarachnoid hemorrhage clinical trials. Transl Stroke Res. 2013;4:286–96.

    Article  Google Scholar 

  26. Dorhout Mees SM, Kerr RS, Rinkel GJ, Algra A, Molyneux AJ. Occurrence and impact of delayed cerebral ischemia after coiling and after clipping in the International Subarachnoid Aneurysm Trial (ISAT). J Neurol. 2012;259:679–83.

    Article  Google Scholar 

  27. Sadan OWH, Moore R, Feng C, Mei Y, Pearce D, Kraft J, Pimentel C, Mathew S, Akbik F, Ameli P, Taylor A, Danyluk L, Martin KS, Garner K, Kolenda J, Pujari A, Asbury W, Jaja B, Macdonald RL, Cawley CM, Barrow DL, Samuels O. Intrathecal nicardipine for cerebral vasospasm post subarachnoid hemorrhage is correlated with reduced delayed cerebral ischemia–a retrospective propensity score-based analysis. J Neurosurg. 2021.

  28. Darsaut TE, Derksen C, Farzin B, et al. Reliability of the diagnosis of cerebral vasospasm using catheter cerebral angiography: a systematic review and inter- and intraobserver study. AJNR Am J Neuroradiol. 2021;42(3):501–7.

    Article  CAS  Google Scholar 

Download references

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Division of Neurocritical Care, Departments of Neurology and Neurosurgery, Emory University School of Medicine, 1364 Clifton Rd NE, Atlanta, GA, 30322, USA

    Feras Akbik, Cederic Pimentel-Farias, Owen B. Samuels & Ofer Sadan

  2. Emory University, Atlanta, GA, USA

    Di’Jonai A. Press, Niara E. Foster, Kevin Luu, Merin G. Williams, Sena G. Andea, Regina K. Kyei & Grace M. Wetsel

  3. Neuroscience Intensive Care Unit, Emory Healthcare, Atlanta, GA, USA

    Feras Akbik, Cederic Pimentel-Farias, Di’Jonai A. Press, Niara E. Foster, Kevin Luu, Merin G. Williams, Sena G. Andea, Regina K. Kyei, Grace M. Wetsel, Jonathan A. Grossberg, Brian M. Howard, Frank Tong, C. Michael Cawley, Owen B. Samuels & Ofer Sadan

  4. Department of Neurosurgery, Emory University Hospital and Emory University School of Medicine, Atlanta, GA, USA

    Jonathan A. Grossberg, Brian M. Howard, Frank Tong & C. Michael Cawley

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  1. Feras Akbik
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  2. Cederic Pimentel-Farias
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  15. Ofer Sadan
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Contributions

FA, CPF, and OS designed the project. FA, CPF, DJAP, NEF, KL, MGW, SGA, RKK, GMW, JAG, BMH, and OS were involved in primary data collection, data analysis, and manuscript preparation. FT, CMC, and OBS were involved in data analysis and critical review of the manuscript. All authors meet established authorship criteria. All authors have reviewed and approved the final manuscript.

Corresponding author

Correspondence to Feras Akbik.

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Akbik, F., Pimentel-Farias, C., Press, D.A. et al. Diffuse Angiogram-Negative Subarachnoid Hemorrhage is Associated with an Intermediate Clinical Course. Neurocrit Care 36, 1002–1010 (2022). https://doi.org/10.1007/s12028-021-01413-y

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