Korean Journal of Cerebrovascular Surgery 2009;11(1):5-11.
Published online March 1, 2009.
Clinical Analysis of Spontaneous Subarachnoid Hemorrhage with Negative Angiography.
Kim, Bum Joon , Park, Kyung Jae , Shin, Il Young , Lee, Hoon Kap , Chung, Yong Gu
Department of Neurosurgery, Anam Hospital, Korea University, College of Medicine, Seoul, Korea. yongku9@chollian.net
Most cases of spontaneous subarachnoid haemorrhage (SAH) are due to a ruptured cerebral aneurysm, yet sometimes the cause of bleeding can be obscure. We report here on the results of a retrospective single-center study to determine the role of the hemorrhage patterns for the patients with a negative angiogram on admission. METHODS : A total of 480 patients with spontaneous subarachnoid hemorrhage (SAH) were admitted from January 2004 to September 2008. Of these, 44 patients were included in this study because of their negative findings on their initial angiography. SAH was diagnosed by a computed tomographic scan or lumbar puncture. The clinical grade was assessed using the Hunt-Hess grading system, Fisher's grading system and the modified Rankin scale. RESULT : The overall incidence of an initially negative angiogram for patients with a spontaneous SAH was 10.2%. Based on the hemorrhage pattern on the admission CT, the most common pattern was the diffuse type (52.3%), followed by the perimesencephalic type (29.5%), the CT negative type (11.4%) and the localized non-perimesencephalic type (6.8%). The repeat angiogram revealed an aneurysm in 3 (7.7%) patients and exploration revealed a dissecting aneruysm of the vertebral artery in 1 patient. The patients with the diffuse type SAH significantly differed from the perimesencephalic group with regard to the Fisher grade (p = 0.002), the outcome at discharge (p = 0.004) and the need for EVD. CONCLUSION : Patients with SAH of an unknown cause, especially with perimesencephalic SAH, have an excellent prognosis and low mortality. We believe that digital subtraction angiogram is still the gold standard for making the diagnosis of aneurysm in patients with spontaneous SAH. A repeat angiogram is recommended for all the patients with initially angionegative SAH. For those patients with perimesencephalic SAH and a positive CSF study with a negative CT, we suggest to perform a CT angiogram as a less invasive follow-up study.
Key Words: Spontaneous subarachnoid hemorrhage, Angio-negative SAH, Non-traumatic SAH, Perimesencephalic SAH, Repeat angiogram


Most cases of spontaneous subarachnoid haemorrhage (SAH) are due to a ruptured cerebral aneurysm. However, the initial angiography fails to reveal any cause of bleeding in up to 30% of SAH patients.6)7)13)17)19)28) Previous studies have concentrated the relationship between distribution of blood

and prognosis. Perimesencephalic SAH as described by Van Gijn et al. is representative of non-aneurysmal SAH, is usually benign and shows an excellent prognosis.29) While some disagreements exist, many authors suggest repeat angiography as a gold standard for the diagnosis of

aneurysm especially in non-perimesencephalic SAH pattern on admission CT scan.1)14)15)19)

The current study was designed not only to determine the number of patients with a false-negative initial angiogram, but also to develop diagnostic and therapeutic strategies by analysing the clinical features, long-term outcomes and radiological findings of 44 patients with SAH who had a negative angiography on initial presentation.

Materials and methods

A total of 480 patients with spontaneous subarachnoid hemorrhage (SAH) were admitted to the Department of Neurosurgery from January 2004 to September 2008. Of these, 44 patients were included in this study for negative findings on initial angiography. SAH was diagnosed by computed tomographic scan or lumbar puncture (xanthochromic fluid). Patients with head injuries, tumor, coagulopathy, infection, vasculitis, and those who received incomplete study due to severe brain swelling were excluded.

All admission CT scan were reviewed, and patients were classified as four categories: diffuse type, perimesencephalic type, localized non-perimesencephalic type and negative CT

scan but confirmed on CSF study.31)32)

Diffuse hematoma

filling the basal cisterns was classified as a diffuse type. Perimesencephalic type was defined as localized hemorrhage in the perimesencephalic cistern or a focus of blood ventral to the brainstem with limited or no filling of the basal cisterns, interhemispheric cistern, and Sylvian cisterns, whereas localized hematoma in the non-perimesencephalic area (ex. interhemispheric cistern, Sylvian cisterns.) without filling basal cisterns was classified as localized nonperimesencephalic (PM) type.20)23)30)

All patients were graded clinically according to the the Hunt-Hess grading system11) at the time of admission, and retrospective grading of initial CT scan using Fisher grading system8) was performed. Functional status at discharge was determined using the modified Rankin scale.

Statistical analysis

For continuous variables, stastistical comparison between the groups were performed using analysis of variance (ANOVA) and Tukey honestly significant difference. For grading systems, nonparametric Kruskal-Wallis and Mann- Whitney test were used. The significance level was set at a P value less than 0.05.


The overall incidence of initially negative angiogram in spontaneous SAH was 10.2% (49/480). Of these 49 patients, five patients expired in a few days as a result of severe brain swelling. On serial CT scans, there was no evidence of rebleeding. They were excluded from following analysis owing to incomplete study. Among the 44 survivors, there were 20 men (45.5%) and 24 women (54.5%), age ranged from 13 to 78 years (mean 56 years). Digital subtraction angiogram (DSA ; Axiom Artis BA, Siemens) was performed in 42 patients and CT angiogram (Brilliance 64 MDCT, Philips) was performed in 37 patients.

Repeat DSA was performed in 33 patient and repeat CT angiogram was performed in 6 patient between 7th and 14th hospitalization day, one patient underwent a third DSA angiogram. Repeat angiogram revealed an aneurysm in 3 (7.7%) patients (A-comm, P-comm and A1 aneurysm were identified.) and exploration revealed a dissecting aneruysm of vertebral artery in one patient(Table 1).

The clinical and CT features of the four groups of patients with initially negative angiogram are listed in Table 2. Based on hemorrhage pattern on admission CT, the most common pattern was diffuse type (52.3%), followed by the perimesencephalic type (29.5%), CT negative type (11.4%) and localized non-PM type (6.8%). The mean age was lowest in CT negative group, but was not statistically significant (P=0.064).

Of the 23 patients in diffuse type, all patients received repeat angiogram and aneurysm was found in 2 (8.7%). In diffuse type, one more aneurysm was revealed during explorative craniotomy. Of the 3 patient in localized non-PM type, 2 patients underwent repeat angiogram and 1 (33.3%) aneurysm was detected. In contrast, of the 13 patients in perimesencephalic type, 12 patients underwent repeat angiogram but no aneurysm was identified. Of the 5 patient in CT negative type, repeat angiogram was performed in 2

patient, and no lesion was detected. Four patients with negative angiogram underwent an exploratory craniotomy. One patient, whose CT scan showed a diffuse pattern, harbored a dissecting aneurysm. Other

three patient had a negative exploration. A total of 5 patients underwent external ventricular drainage of CSF due to symptomatic hydrocephalus, all patients were in diffuse group. Patients with diffuse SAH differed significantly from the perimesencephalic group with regard to Fisher grade (p=0.001), outcome at discharge (p=0.006) and need for EVD. The average of follow-up period was 30 months. During

follow-up period, no episode of recurrent SAH was observed.

Illustrative cases

Case 1

A 45-year old man presented with Hunt-Hess grade 1 and Fisher grade 3 diffuse type subarachnoid hemorrhage. His initial DSA failed to detect aneurysm. DSA on hospitalization day 15 revealed a saccular aneurysm of left anterior communicating artery (Fig. 1). Intraoperatively, partially thrombosed aneurysm was confirmed. One week later, he was discharged without any neurologic deficit.

Case 2

A 59-year old man presented with Hunt-Hess grade 2 and Fisher grade 4 diffuse type subarachnoid hemorrhage. His initial DSA and three-dimensional CT angiography were negative. Repeated DSA on hospitalization day 7 was also negative (Fig. 2). He was discharged without any neurologic deficit. Ten days later, he was found as a comatose patient.

CT scan showed extensive rebleeding in basal cisterns and fouth ventricle, repeated CT angiography revealed nonspecific stenosis of the right vertebral artery. Suboccipital decompression was performed and exploration revealed a dissecting aneurysm of the right vertebral artery which was not explored during previous conventional angiography due to poor visualization. Intraoperatively, massive hemostasis

and wrapping were performed. After several months of intensive care and rehabilitation, he was neurologically improved up to mRS 3.


In patients with spontaneous subarachnoid hemorrhage, initial cerebral angiography occasionally fails to reveal any causative lesions, and rate of failure to detect an aneurysm of 6~30% have been reported.6)7)17)22)

In the present study, the incidence of false-negative initial angiography was 9.0%. In most of these cases, the cause of the SAH remains unknown even after repeat angiography. However, in a small

percentage of such patients, repeat angiography reveals a lesion not detected on the initial angiography.

It is well documented that the prognosis of aneurysmal SAH markedly differs from that of nonaneurysmal SAH. Unoperated ruptured aneurysms bear a high risk of rebleeding estimated up to 50% during the first 6 months after haemorrhage. Hence, when the cause of the haemorrhage cannot be found on the first cerebral angiogram it is important to discriminate whether the angiogram is false-negative, or whether the haemorrhage is a result of other unknown causes. It has been demonstrated that failure to detect aneurysm is attributed to vasospasm, spontaneous thrombosis, arterial dissection, destruction of the aneurysm by hemorrhage, microaneurysms too small to be opacified, and inadequate angiographic technique. Previous studies have reported rates of detection by repeat angiography of initially false-negative angiography of 6~36%.5)6)12)15)19)28)

The rate may vary from institution to institution, depending on the timing of the initial and repeat angiography, inclusion criteria of SAH patients for angiography, referral pattern of SAH patients, and also on the resolution of the angiograms in each institution.12) In present study, the rate was 7% (3/44).

Perimesencephalic SAH as described by Van Gijn et al. is representative of non-aneurysmal SAH which is known to have almost no risk of rebleeding, and is associated with good recovery. In the literature, the incidence of perimesencephalic SAH among positive CT studies varies from 30% to 68%.5)24)27) In present study, the incidence of perimesencephalic SAH was 29.5%. Even though Kallmes et al reported that the mean frequency of perimesencephalic pattern of subarachnoid hemorrhage in ruptured

vertebrobasilar aneurysms was 7.1% (48/676 readings),16) in our experience, we could not detect any aneurysm in perimesencephalic group.

The outcome for patients with SAH of unknown cause is generally good. In the present study, 90.9% (40/44) of the patients remained as SAH of unknown cause. All of these had a good recovery and there was no rebleeding during follow-up period. These findings are consistent with previous reports.4)23) Delayed cerebral ischemia is a common complication of aneurysmal SAH.4)10) In contrast, in patients

with SAH of unknown cause, incidence of delayed ischemia ranges from 4% to 10%.4)5)10) In our series, there was no patient who suffered definite ischemia in angionegative group.

Urbach et al suggested that dissecting aneurysm of the intracranial vertebral or basilar artery, known to present with SAH in up to 4.5% of cases may resemble spasm and most angiograms in this condition show a fusiform dilatation of the vertebral or basilar artery with irregular proximal and/or distal narrowing.28) We experienced one patient who was misdiagnosed even after three times of angiography.

Explorative craniotomy revealed a dissecting aneurysm of the right vertebral artery which was not detected during previous conventional angiogram. If the contrast did not reflux down the contralateral vertebral artery, both vertebral arteries must be explored. Controversies exist in the value of MRI in the

management of SAH. Berdoz et al reported that no cranial MRI revealed an underlying lesion responsible for the haemorrhage.2) In contrast, Little et al proposed that MRI scans may help confirm the diagnosis of SAH in patients diagnosed by lumbar puncture and MRI scanning of the cervical spine may help determine the origin of SAH in selected cases.20) In the present study, 6 patients with negative angiogram underwent cranial MRI and MR angiogram. No patient showed the cause of bleeding on MR

imagies. Recent prospective studies concerning the complication rate of cerebral angiography revealed permanent neurological deficits in 0.09~0.5%.28) Urbach et al demonstrated the rate of neurological complications nowadays is much lower than in earlier reports by shortening of the procedure and suggested repeat angiography early in the course whenever features such as spasms, haematoma or

brain oedema is present.28) Several authors have recommended screening for intracranial aneurysms in high-risk groups, namely polycystic kidney disease patients and those with a strong family history of aneurysmal SAH.3)18)25)33) The mortality and morbidity in cases treated before rupture is significantly

lower than after SAH.9) Although controversies exist in costeffectiveness of routine screening,21)26) we believe that welldesigned screening programs could save many lives. The present study corroborates the generally good prognosis of patients with SAH of perimesencephalic pattern in initial CT, with a low mortality rate and a minimal risk of rebleeding. In these group, treatment should be symptomatic

and repeat CT angiogram is recommended as a less invasive diagnostic tool. Nevertheless, it should be kept in mind that diagnosis of non-aneurysmal SAH is one of exclusion, based principally on a normal, detailed initial angiogram and that the review of the angiographic films must be meticulous. At

present, we think repeat DSA is advised only if there is strong suspicion of an aneurysmal SAH on initial CT scan.


The present study reinforce that patients with SAH of unknown cause, especially with perimesencephalic SAH, have an excellent prognosis and low mortality. The finding that localized non-PM group differed from the perimesencephalic group with regard to false-negative rate must be verified on further studies. We believe that the digital subtraction angiogram is still a gold standard for diagnosis of aneurysm in spontaneous SAH patients and meticulous review of angiography by experienced clinician is also important. In performing DSA, if the contrast did not reflux down the contralateral vertebral artery, both vertebral arteries must be explored.

Because ruptured posterior fossa aneurysms manifest with the nonaneurysmal pattern of hemorrhage in approximately 10% of cases,16) repeat angiogram is recommended for all patients with initially angionegative SAH. In perimesencephalic and CT negative SAH patients, we suggest CT angiogram as a less invasive follow-up study.


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