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Zerega M, et al. Hemorragia Subaracnoídea no Traumática con Angiografía por tomografía computada inicial “Ne-gativa”. Rev Chil Radiol 2018; 24(3): 94-104.Correspondence: Juan Pablo Cruz Quiroga / jpcruz@med.puc.clWork sent 07 september 2018. Accepted for publication 28 september 2018.

IntroductionNon-traumatic subarachnoid hemorrhage (SAH)

is a subtype of hemorrhagic stroke that accounts for

approximately 5% of all cerebrovascular accidents (CVA). 80-85% of cases of SAH are secondary to a ruptured intracranial aneurysm and 10% to non-

Non-Traumatic Subarachnoid Hemorrhage with “Negative” Initial Computed Tomography Angiography

Mario Zerega Ruiz1, Karin Müller Campos1, Rodrigo Rivera Miranda2, Sebastián Bravo Grau3, Juan Pablo Cruz Quiroga3.

1. Resident of Subspecialty in Diagnostic Neuroradiology, Radiology Department, Medical Faculty, Pontificia Universidad Católica de Chile. Santiago, Chile.

2. Neuroradiology Service, Institute of Neurosurgery Dr. Alfonso Asenjo. Santiago, Chile.3. Radiology Department, Medical Faculty, Pontificia Universidad Católica de Chile. Santiago, Chile.

Hemorragia Subaracnoídea no Traumática con Angiografía por tomografía computada inicial “Negativa”

ResumenLa hemorragia subaracnoidea (HSA) no traumática es un subtipo de ictus hemorrágico que representa aproximadamente el 5% de todos los accidentes vasculares encefálicos (AVE). El 85% de los casos de HSA espontánea (no traumática) son secundarios a un aneurisma intracraneano roto, el 10% a hemorragia perimesencefálica no aneurismática y el otro 5% a otras causas. Entre estas se incluyen malformaciones arterio-venosas, fístulas durales, vasculits, trombosis de vena cortical, síndrome de vasoconstricción reversible, angiopatía amiloidea y síndrome de encefalopatía posterior reversible.La aproximación inicial a una HSA no traumática requiere un estudio angiográfico no invasivo con tomogra-fía computada para la toma de decisiones terapéuticas. Si no se detecta un aneurisma sacular intradural que explique el sangrado, las conductas a seguir dependerán del patrón de distribución de la sangre. En esta revisión sugerimos una aproximación basada en 1) revisar el estudio inicial tomando en cuenta los puntos ciegos para la detección de aneurismas, 2) analizar el patrón de distribución de la sangre y 3) analizar los hallazgos en imágenes de acuerdo a las posibles causas según patrón.Palabras clave: hemorragia subaracnoidea, angio TC, vasculitis, vasoconstricción cerebral reversible, trombosis venosa cortical, angiopatía amiloidea.

AbstractNon-traumatic subarachnoid hemorrhage represents approximately 5% of strokes. From these, 85% of nontraumatic subarachnoid hemorrhage are secondary to a ruptured aneurysm, 10% to nonaneurysmal perimesencephalic hemorrhage and the other 5% to other causes. These include but are not limited to arteriovenous malformations, dural fistulae, vasculitis, cortical vein thrombosis, reversible cerebral vaso-constriction syndrome, amyloid angiopathy and posterior reversible encephalopathy syndrome.Initial workup of nontraumatic subarachnoid hemorrhage requires a non-enhanced CT and CT angiography for decision making and management. If there is no aneurysm as a source of hemorrhage, subsequent imaging studies will depend on blood distribution pattern. In this review we suggest an approach: 1) review blind spots for aneurysm detection in the initial CT angiography, 2) analyze blood distribution pattern and 3) evaluate imaging findings and possible causes according to each pattern.Keywords: subarachnoid hemorrhage, CT angiography, vasculitis, reversible cerebral vasoconstriction syndrome, cortical vein thrombosis, amyloid angiopathy.

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aneurysmal perimesencephalic hemorrhage(1). 5% is secondary to other causes(2), including arterio-venous malformations, dural fistulas, vasculitis, cortical vein thrombosis and reversible vasoconstriction syndrome.

The initial approach to a non-traumatic SAH requires a non-invasive angiographic study with computed tomography (CT) for therapeutic decision making and risk stratification. In cases in which the CT angiography does not show an intradural saccular aneurysm that explains the bleeding, the course of action will depend on the blood distribution pattern (aneurysmal, perimesencephalic, convexal).

The concept of “negative” CT angiography is not synonymous with an examination without visible aneurysms. There are multiple other causes of non-traumatic SAH with associated findings in CT and magnetic resonance imaging (MRI) studies(3), which may be subtle and require a clinical suspicion to im-prove their diagnostic investigation by the radiologist.

In this review we suggest an approach based on 1) review the initial study taking into account the blind spots for the detection of aneurysms, 2) analyze the blood distribution pattern and 3) analyze the imaging findings for possible causes according to the pattern.

1. Blind spots of aneurysmsAs stated in the introduction, all non-traumatic

SAH should be evaluated initially with a CT angiogram (CTA) to look for a possible aneurysm. The sensitivity of CT angiography for the detection of aneurysms is 98% with a specificity close to 100%(4).

The typical locations of ruptured saccular aneu-rysms are(5,6): 1) anterior communicating artery system (~ 30%), 2) posterior communicating artery (~ 20%), 3) “top” of the basilar artery (~ 15%) and 4) middle cerebral artery (~ 12%). Other locations

include the ICA bifurcation and ophthalmic carotid, which are more common sites in populations with unruptured aneurysms.

False negative interpretations of a CTA are more frequent in the following situations(4,7): 1) small aneurysms

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Figure 3: SAH secondary to ruptured dissecting aneurysm of right vertebral artery. Axial slice (A) of CT shows SAH in prebulbar cisterns. The coronal MIP reconstructions (B) and 3D CT angiography MIP show SAH in the posterior fossa and alternating fusiform dilation with areas of stenosis of the right intracranial vertebral artery, characteristic findings for a transmural dissection.

Figure 2: Partial thrombosed saccular aneurysm of left supraclinoid ICA. Coronal MIP reconstructions (A) of CT angiography, 3D contrast-enhanced MR angiography MIP image (B) and coronal TSE T2 MRI slice. The opacification of the partially thrombosed aneurysm is barely visible in CT angiography and evident in MR angiography. However, none of these techniques allows visualization of the complete aneurysmal sac. The coronal TSE T2 MRI sequence shows a predominantly hypointense thrombus inside the sac.

Figure 4: “Blister” type aneurysm. The axial slice (A) in CT shows SAH in basal cisterns and hydrocephalus with ventricular dilation and collapse of the convexity sulci. Axial (B) and sagittal (C) CT angiography reconstructions show an irregular surfaced sessile projection of left clinoid ICA with lateral and caudal orientation.

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Figure 6: Blood distribution patterns in non-traumatic SAH. A perimesencefálico pattern. B aneurysmal pattern. C convexal pattern.

Figure 5: Axial CT slices (A, B and C) of a patient with a history of bacterial endocarditis show SAHs of the left convexity and sylvian fissure, and an ipsilateral frontoparietal parenchymal hematoma. Axial reconstructions (D) and coronal CT angiogram MIP (E) show a small 2 mm ruptured mycotic aneurysm of the precentral branch of the left superior MCA division. 3D MIP reconstruction shows absence of proximal saccular aneurysms.

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2. Extension only to the posterior aspect of the interhemispheric fissure.

3. Extension only to the medial aspect of the silvian fissures.

4. Absence of intraventricular clot. Small volume of blood is accepted in dependent portions of the occipital horns.

5. Absence of parenchymal hematoma.6. Good negative quality angiographic study.

this is negative, it is not necessary to perform more tests, since patients do not benefit from repeating both invasive and non-invasive studies.

Patients presenting with clinical findings attributable to myelopathy should be studied with MRI and cervical MR angiography to rule out a cervical dural fistula. This can simulate a perimesencephalic hemorrhage in images (Figure 8)(15,16).

2.2. Aneurysmal patternAn aneurysmal pattern is any non-traumatic SAH

with compromise of the basal cisterns that does not meet the criteria for a perimesencephalic pattern (Figure 9). These patients should be considered and managed under the assumption that they have a rup-tured aneurysm, so performing a diagnostic cerebral DSA is mandatory in this subgroup. Up to 46% of these patients will have an aneurysm on angiogra-phy repeated at 7 days and in 1/3 of these cases the aneurysm was visible in the initial study(7). They tend to be aneurysms

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2.3. Convexal patternIt is defined as an SAH limited to the convexity

sulci, without compromise of the basal cisterns. The differential diagnosis is broad and the most relevant

diseases that can give this pattern include:• Reversible vasoconstriction syndrome (RVCS).

RVCS is a noninflammatory arteriopathy that presents as a clinical manifestation common

Figure 9: Aneurysmal pattern SAH. Axial CT slices without contrast (A and B) show SAH in suprasellar, silvian, anterior interhemispheric, cranial and interpeduncular cisterns, blood content in the IV ventricle and prepontine cisterns. The sagittal CT angiography MIP reconstruction shows a small anterior communicating complex aneurysm smaller than 2 mm (white arrow).

Figure 10: Axial (A, C) and sagittal (B) slices of non-contrasted computed tomography show an aneurysmal pattern SAH predominantly in the posterior fossa. At the level of C1-C2 (C) a clot is observed in the right lateralized spinal canal, which displaces the spinal cord to the left. The coronal MIP (D) and 3D MIP (E) reconstructions of the CT angiogram show an arteriovenous fistula of the right craniofacial cervical junction C1-C2 that is the cause of the SAH.

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to several disease processes, characterized by ictal headache and multifocal vasocons-triction, which by definition resolves within a period of 3 months(20). Convexal SAH is the most common hemorrhagic manifestation of this condition. CT angiography and DSA show multifocal stenosis of small vessels(21), which evolves with a centripetal migration of the alterations during the first week(22). The control tests show normalization of the caliber at 3 months.

• Posterior Reversible Encephalopathy Syndrome (PRES). PRES is a clinical profile characteri-zed by encephalopathy associated with areas of cerebral parenchymal edema in areas of borderline territory, which predominate in the posterior territory(23). Patients with hyperten-sive PRES may present with convexal SAH in 5-17% due to rupture of pial vessels due to loss of self-regulation of cerebral blood flow. Associated findings in CT include bilateral cortical subcortical multifocal hypodensities in superficial border territory (parieto-occipital, superior frontal paramedians), which can be better evaluated with MRI, where parenchy-matous edema is identified, with hyper-signal in DWI and positive values in the ADC map (vasogenic edema), and there may be areas of associated cytotoxic edema (low values in the ADC map)(24) (Figure 11).

• Cortical vein thrombosis. Sulcal SAH is pro-gressively recognized as presenting cortical or dural venous sinus thrombosis, although the mechanism is not clearly elucidated(25). 6.4% present with isolated SAH and 4.6% have associated parenchymal abnormalities (subcortical cortical edema with or without hemorrhagic infarction)(26). These alterations

are better evaluated with MRI because of the intrinsic advantages of contrast resolution. In case of doubt, the elective examination is MR venography with the use of contrast medium(27) (Figure 12).

• CNS Vasculitis (primary or secondary). This is a heterogeneous and infrequent group of SAH. They represent

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with inflammatory changes associated with amyloid β deposition) (Figure 14).

• Recreational drugs use. The use of recrea-tional drugs usually triggers the rupture of a pre-existing lesion. Any sympathomimetic drug can induce hypertension and convexal SAH. Cocaine is the most frequent among these drugs and is an independent factor of worst prognosis in SAH. Patients deve-lop aneurysms in 40-70%, therefore, the pattern is usually aneurysmal(33). Patients also may develop a drug induced vasculitis demonstrated in histological and in vessel

wall imaging studies(34), which explains the convexal pattern.

Bibliography1. Bederson JB, Connolly ES, Batjer HH, Dacey RG,

Dion JE, Diringer MN, et al. Guidelines for the mana-gement of aneurysmal subarachnoid hemorrhage: A statement for healthcare professionals from a special writing group of the stroke council, American heart association. Stroke. 2009; 40(3): 994-1025.

2. Provenzale JM, Hacein-Bey L. CT evaluation of subarachnoid hemorrhage: A practical review for the radiologist interpreting emergency room studies. Emergency Radiology. 2009; 16: 441-451

3. Marder CP, Narla V, Fink JR, Tozer Fink KR. Subara-

Figure 12: Venous thrombosis of the superior sagittal sinus. Axial slices of CT (A) and T2 FLAIR MR sequence (B) show SAH in sulci of the right frontoparietal convexity, associated with hyperdensity (CT) and loss of flow void (FLAIR) of the posterior aspect of the superior sagittal sinus. The T1 sagittal slice gradient after MRI contrast confirms a filling defect in the superior sagittal sinus associated with pachymeningeal thickening and venous engorgement.

Figure 13: Secondary CNS vasculitis due to systemic lupus erythematosus. The axial T2 FLAIR slices sequences (A) and MR susceptibility (B and C) show SAH in occipital and parietal sulcus, associated with multiple bilateral subcortical cerebellar and occipital microhemorrhages.

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Figure 14: Amyloid angiopathy with convexal SAH. Axial CT slices without contrast (A) T2 FLAIR sequences (B) and T2* MR (C) show SAH in the right precentral sulcus, with bilateral frontoparietal superficial pial siderosis, as a manifestation of previous bleedings.

Modified proposed algorithm of Agid et al(8).

chnoid hemorrhage: Beyond aneurysms. American Journal of Roentgenology. 2014; 202: 25-37.

4. Westerlaan HE, van Dijk JMC, van Dijk MJ, Jansen-

van der Weide MC, de Groot JC, Groen RJM, et al. Intracranial aneurysms in patients with subarachnoid hemorrhage: CT angiography as a primary exa-

103

ARTÍCULO REVISIÓNRev Chil Radiol 2018; 24(3): 94-104.

mination tool for diagnosis-systematic review and meta-analysis. Radiology. 2011; 258(1): 134-145.

5. Molyneux AJ, Kerr RS, Yu LM, Clarke M, Sneade M, Yarnold JA, et al. International Subarachnoid Aneu-rysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and. Lancet. 2005; 366(9488): 809-817.

6. Forget TR, Benitez R, Veznedaroglu E, Sharan A, Mitchell W, Silva M, et al. A review of size and location of ruptured intracranial aneurysms. Neurosurgery. 2001; 49(6):1322-1325.

7. Jung JY, Kim YB, Lee JW, Huh SK, Lee KC. Spon-taneous subarachnoid haemorrhage with negative initial angiography: A review of 143 cases. J Clin Neurosci. 2006; 13(10): 1011-1017.

8. SK, TerBrugge KG, et al. Negative CT Angiography Findings in Patients with Spontaneous Subarachnoid Hemorrhage: When Is Digital Subtraction Angiogra-phy Still Needed? Am J Neuroradiol. 2010; 31(4): 696-705.

9. van Gijn J, van Dongen KJ, Vermeulen M, Hijdra A. Perimesencephalic hemorrhage: a nonaneurysmal and benign form of subarachnoid hemorrhage. Neu-rology. 1985; 35(4): 493-497.

10. Flaherty ML, Haverbusch M, Kissela B, Kleindorfer D, Schneider A, Sekar P, et al. Perimesencephalic subarachnoid hemorrhage: Incidence, risk factors, and outcome. J Stroke Cerebrovasc Dis. 2005; 14(6): 267-271.

11. Schwartz TH, Solomon RA. Perimesencephalic no-naneurysmal subarachnoid hemorrhage: Review of the literature. Neurosurgery. 1996; 39(3): 433-440.

12. Kershenovich A, Rappaport ZH, Maimon S. Brain computed tomography angiographic scans as the sole diagnostic examination for excluding aneurysms in patients with perimesencephalic subarachnoid hemorrhage. Neurosurgery. 2006; 59(4): 798-801.

13. Cruz JP, Sarma D, Noel De Tilly L. Perimesencephalic subarachnoid hemorrhage: When to stop imaging? Emerg Radiol. 2011; 18(3): 197-202.

14. Mensing LA, Vergouwen MDI, Laban KG, Ruigrok YM, Velthuis BK, Algra A, et al. Perimesencephalic Hemorrhage: A Review of Epidemiology, Risk Factors, Presumed Cause, Clinical Course, and Outcome. Stroke. 2018; 1-9.

15. Hashimoto H, Lida JI, Shin Y, Hironaka Y, Sakaki T. Spinal durai arteriovenous fistula with perimesen-cephalic subarachnoid haemorrhage. J Clin Neurosci. 2000; 7(1): 64-66.

16. Wijdicks EFM, Schievink WI, Miller GM. MR imaging in pretruncal nonaneurysmal subarachnoid hemorrhage: Is it worthwhile? Stroke. 1998; 29(12): 2514-2516.

17. Rodriguez-Régent C, Edjlali-Goujon M, Trystram D, Boulouis G, Ben Hassen W, Godon-Hardy S, et al. Non-invasive diagnosis of intracranial aneurysms. Diagn Interv Imaging. 2014; 95(12): 1163-1174.

18. Lasjaunias P, Chiu M, Ter Brugge K, Tolia A, Hurth M, Bernstein M. Neurological manifestations of intracranial dural arteriovenous malformations. J Neurosurg. 1986; 64(5): 724-730.

19. Hiramatsu M, Sugiu K, Ishiguro T, Kiyosue H, Sato

K, Takai K, et al. Angioarchitecture of arteriovenous fistulas at the craniocervical junction: a multicenter cohort study of 54 patients. J Neurosurg. 2017; 128(June): 1-11.

20. Miller TR, Shivashankar R, Mossa-Basha M, Gandhi D. Reversible cerebral vasoconstriction syndrome, part 1: Epidemiology, pathogenesis, and clinical course. Am J Neuroradiol. 2015; 36(8): 1392-1399.

21. Ducros A, Fiedler U, Porcher R, Boukobza M, Stapf C, Bousser MG. Hemorrhagic manifestations of reversible cerebral vasoconstriction syndrome: Frequency, features, and risk factors. Stroke. 2010; 41(11): 2505-2511.

22. Shimoda M, Oda S, Hirayama A, Imai M, Komatsu F, Hoshikawa K, et al. Centripetal propagation of vasoconstriction at the time of headache resolution in patients with reversible cerebral vasoconstriction syndrome. Am J Neuroradiol. 2016; 37(9): 1594-1598.

23. Bartynski WS. Posterior Reversible Encephalopathy Syndrome, Part 1: Fundamental Imaging and Clinical Features. Am J Neuroradiol. 2008; 29(6): 1036-1042.

24. Hefzy HM, Bartynski WS, Boardman JF, Lacomis D. Hemorrhage in Posterior Reversible Encephalopathy Syndrome: Imaging and Clinical Features. Am J Neuroradiol. 2009; 30(7): 1371-1379.

25. Oppenheim C, Domigo V, Gauvrit J-Y, Lamy C, Mackowiak-Cordoliani M-A, Pruvo J-P, et al. Suba-rachnoid hemorrhage as the initial presentation of dural sinus thrombosis. AJNR Am J Neuroradiol. 2005; 26(3): 614-617.

26. Boukobza M, Crassard I, Bousser MG, Chabriat H. Radiological findings in cerebral venous thrombosis presenting as subarachnoid hemorrhage: a series of 22 cases. Neuroradiology. 2016; 58(1): 11-16.

27. Farb RI, Scott JN, Willinsky R a, Montanera WJ, Wright G a, TerBrugge KG. Intracranial venous system: Gadolinium-enhanced three-dimensional MR venography with auto-triggered elliptic centric-ordered sequence-initial experience. Radiology. 2003; 226(1): 203-209.

28. Calabrese LH. Diagnostic strategies in vasculitis affecting the central nervous system. Cleve Clin J Med. 2002; 69(2): SII105-108.

29. Mandell DM, Mossa-Basha M, Qiao Y, Hess CP, Hui F, Matouk C, et al. Intracranial vessel wall MRI: Principles and expert consensus recommendations of the American society of neuroradiology. American Journal of Neuroradiology. 2017; 38: 218-229.

30. Linn J, Halpin A, Demaerel P, Ruhland J, Giese AD, Dichgans M, et al. Prevalence of superficial side-rosis in patients with cerebral amyloid angiopathy. Neurology. 2010; 74(17): 1346-1350.

31. Salvarani C, Morris JM, Giannini C, Brown RD, Christianson T, Hunder GG. Imaging Findings of Cerebral Amyloid Angiopathy, Aβ-Related Angiitis (ABRA), and Cerebral Amyloid Angiopathy-Related Inflammation. Medicine (Baltimore). 2016; 95(20): e3613.

32. Moussaddy A, Levy A, Strbian D, Sundararajan S, Berthelet F, Lanthier S. Inflammatory Cerebral Amyloid Angiopathy, Amyloid-β-Related Angiitis, and Primary Angiitis of the Central Nervous System: Similarities and Differences. Stroke. 2015; 46(9): e210-213.

33. Chang TR, Kowalski RG, Caserta F, Carhuapoma JR,

Rev Chil Radiol 2018; 24(3): 94-104.

104

Tamargo RJ, Naval NS. Impact of acute cocaine use on aneurysmal subarachnoid hemorrhage. Stroke. 2013; 44(7): 1825-1829.

34. Abdel Razek AAK, Alvarez H, Bagg S, Refaat S, Castillo M. Imaging Spectrum of CNS Vasculitis. RadioGraphics. 2014; 34(4): 873-894.