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Subarachnoid Hemorrhage of Unknown Etiology

Management | Etiology of angiogram-negative subarachnoid hemorrhage | Recent advances
| Definition: The diagnosis of subarachnoid hemorrhage | Other sources of information

Ten to twenty percent of patients with a spontaneous subarachnoid hemorrhage will have a normal cerebral angiogram and no source of hemorrhage apparent on other neuroimaging studies. Subarachnoid hemorrhage with an initially negative cerebral angiogram has a more benign prognosis than untreated aneurysmal subarachnoid hemorrhage. Nonetheless, a small percentage of such patients experience morbidity or mortality because of recurrent hemorrhage presumably from an undetected aneurysm. This has lead to the common practice of repeating angiography in patients whose initial imaging studies reveal no vascular malformations.

At the M.G.H. Aneurysm/AVM Center a second angiogram is usually obtained approximately two weeks after subarachnoid hemorrhage in patients whose initial studies do not reveal a source of bleeding. A third angiogram is obtained several months later if the clinical suspicion is high or if vasospasm was observed in one or both of the initial studies. Magnetic resonance imaging of the entire neuraxis is often performed to rule out other sources of subarachnoid bleeding including tumors and occult vascular malformations of the brain or spine. If the pattern of blood on computed tomography is consistent with a spinal source, myelography and spinal angiography are performed in an effort to detect a treatable source of future hemorrhage.


Patients with so-called angiogram-negative subarachnoid hemorrhage are at risk for any of the potential complications seen in aneurysmal subarachnoid hemorrhage. These include the development of delayed neurologic deficits (stroke) due to cerebral vasospasm, hydrocephalus, deep venous thrombosis, pulmonary embolism, and respiratory depression. In addition there is a small but real risk of re-hemorrhage. Thus, these patients usually require several weeks of careful monitoring to assure adequate blood pressure control and prompt treatment of vasospasm. They also require long term follow-up to rule out the late onset of hydrocephalus if the amount of initial hemorrhage is significant.

Adequate hydration as well as early mobilization with adequate control of blood pressure are the best current methods of prophylaxis against deep venous thrombosis and resultant pulmonary embolism. In patients whose neurologic or medical status does not allow mobilization, pneumatic compression stockings are an alternative. Stool softeners have also been used traditionally, in an effort to prevent transient elevations of arterial pressure in association with straining.

Most patients with angiogram-negative subarachnoid hemorrhage are treated with the calcium channel antagonist Nimodipine® for 21 days to lessen the risk of a permanent delayed neurologic deficit. The anti-fibrinolytic, epsilon amino-caproic acid (Amicar®), is avoided in this population as most authorities agree that the potential risks of thrombotic complications outweigh the potential benefits of reduced re-hemorrhage rate.

Etiology of angiogram-negative subarachnoid hemorrhage:

A number of causes of angiographically-occult subarachnoid hemorrhage have been observed or proposed. These include: venous or sinus thrombosis; tumors in the brain, spine, or subarachnoid space; infections; blood dyscrasias including anticoagulants and sporadic responses to drugs such as Prozac®; trauma; spinal or cerebral dural or parenchymal vascular malformation; nonvisualized aneurysm-due to vasospasm or thrombosis; and rupture of a small superficial artery.

As the majority of these sources are detected by modern imaging techniques current consensus favors the latter two causes as the most frequent sources of angiogram negative hemorrhage. It is likely that the two have different prognostic implications. Rupture of a small superficial artery is presumed to result in obliteration of the source of hemorrhage with little risk of recurrent bleeding. In distinction, an undetected aneurysm poses a significant risk of re- hemorrhage with potentially catastrophic results.

Recent advances:

The pattern of subarachnoid blood on computed tomography may give clues to the source of hemorrhage as shown in the figure. Recent evidence indicates that blood limited to the perimesencephalic and chiasmatic cisterns without significant extension into the Sylvian fissure or interhemispheric fissure is unlikely to represent an aneurysmal hemorrhage. This pattern of blood likely represents rupture and subsequent thrombosis of a small artery which arises directly from the basilar artery or the Circle of Willis. In distinction, diffuse subarachnoid hemorrhage with blood extending into the Sylvian and interhemispheric fissures is more likely to represent aneurysmal hemorrhage.

Several mechanisms have been proposed for the occasional failure of angiography to detect such aneurysms, including: thrombosis of the aneurysm, local vasospasm, and obliteration of the aneurysm by the rupture. In each of these cases the patient remains at risk of re-rupture due to resumption of filling of the vascular defect by arterial blood.

Given the small risks associated with surgery and the potentially catastrophic results of aneurysmal rupture patients with an aneurysmal pattern of blood are frequently surgically explored. Patients who do not undergo exploration continue to be followed periodically by neuroimaging in an effort to detect an aneurysm. Recent experience at the Aneurysm/AVM Center indicates that the majority of patients who undergo surgery after having an aneurysmal- pattern of blood on computed tomography but negative angiography have an aneurysm discovered and obliterated at surgery. Patient's undergoing these procedures have returned to their normal activities with increased confidence in being free from future subarachnoid hemorrhage

Figure legend. Angiogram-negative subarachnoid hemorrhage classically displays the pattern of blood demonstrated in the images above (top panels). Occasionally, the blood will extend beyond the peri-mesencephalic cisterns as demonstrated on the lower two panels. Our recent experience suggests that in many such cases exploration will reveal a small aneurysm as the source of hemorrhage. At surgery an anterior communicating artery aneurysm was discovered in the patient whose CT is shown in the bottom panels.

Other Information sources on angiogram-negative subarachnoiud hemorrhage:

Further information, including citations to the medical literature can be found in Tatter SB , Crowell RM, Ogilvy CS (1995). Aneurysmal and microaneurysmal angiogram-negative subarachnoid hemorrhage. Neurosurgery . in press.

Definition: The diagnosis of subarachnoid hemorrhage

A high percentage of patients with subarachnoid hemorrhage present acutely complaining of the sudden onset of the worst headache of their life. This is frequently followed by photophobia, nausea, and vomiting. Meningismus is very frequently the only abnormality on examination. In this population current generation computed tomographic scanners detect almost all subarachnoid hemorrhages. If the clinical suspicion of subarachnoid hemorrhage remains high a lumbar puncture may then be performed. Frequently the results of lumbar puncture are equivocal because of a so-called traumatic tap, during which blood is introduced into the lumbar subarachnoid space.

The presence of xanthochromia in the spun sample often confirms the diagnosis of subarachnoid hemorrhage in such cases. Xanthochromia, however, only becomes apparent twelve or more hours after subarachnoid hemorrhage. Clearing of the blood as more samples are collected often allows subarachnoid hemorrhage to be excluded.

In cases where the CSF RBC count does not trend toward zero and when there is no xanthochromia, acute subarachnoid hemorrhage remains a diagnostic possibility. Currently, such patients are often managed as if they have had a subarachnoid hemorrhage. In the future, it is likely that sensitive biochemical tests-such as determination of CSF D-dimer-will allow more patients to be spared the risks of cerebral angiography and the expense of hospitalization and treatment with calcium channel blockers.

Disclaimer About Medical Information: The information and reference materials contained herein is intended solely for the information of the reader. It should not be used for treatment purposes, but rather for discussion with the patient's own physician. All visitors to this and associated sites from the Neurosurgical Service at MGH agree to read and abide by the the complete terms of legal agreement found at the Neurosurgery "disclaimer & legal agreement." See also: the MGH Disclaimer, the MGH Privacy Policy, and the MGH Interactive Program Disclaimer - © Copyright 2006.
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