INTRODUCTION — Subarachnoid hemorrhage (SAH) refers to bleeding within the subarachnoid space, which lies between the arachnoid and pia mater and is normally filled with cerebrospinal fluid. Most cases of SAH are caused by rupture of an intracranial aneurysm. Approximately 15 to 20 percent of patients presenting with SAH do not have a vascular lesion on initial four-vessel cerebral angiography [1,2]. The causes of these nonaneurysmal SAH (NASAH) are potentially diverse, and the mechanism of bleeding in these cases is often not identified.

This topic discusses NASAH. Aneurysmal SAH and perimesencephalic SAH are discussed separately. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis" and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)

ETIOLOGIES

Perimesencephalic nonaneurysmal subarachnoid hemorrhage — A subtype of NASAH, so-called perimesencephalic NASAH is characterized by a specific pattern of localized blood on CT, normal cerebral angiography, and a benign course that distinguishes these patients not only from aneurysmal SAH, but also from other patients with NASAH [2-5]. In some case series, perimesencephalic NASAH makes up the majority, up to two-thirds, of patients with NASAH [1].

The CT findings that define perimesencephalic NASAH include blood isolated to the perimesencephalic cisterns anterior to the brainstem; there may be extension into the ambient cisterns or basal parts of the sylvian fissures, but not into the lateral sylvian fissure, anterior interhemispheric fissure, or lateral ventricles (image 1) [1,5].

Perimesencephalic NASAH is discussed separately. (See "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)

Occult aneurysm — Some cases of perimesencephalic NASAH are caused by an occult aneurysm that is not observed on initial angiography but may be found on repeat angiography (see 'Repeat angiography' below). Reasons for an initial false-negative angiogram include technical or reading errors, small aneurysm size, and obscuration of the aneurysm because of vasospasm, hematoma, or thrombosis within the aneurysm [1,2,6,7].

Vascular malformations — Less than 10 percent of SAH are caused by vascular malformations [6,8]. These can be intracranial or spinal in location.

Intracranial — Intracranial vascular malformations include both acquired and congenital lesions; the latter are more common. These typically exist within the brain parenchyma and produce intracerebral hemorrhage. However, depending on the location of the vascular lesion, bleeding can be primarily or exclusively in the subarachnoid space [6,9-12].

Rebleeding occurs in more than half of patients. Rebleeding from arteriovenous malformations is less likely to be acute than with aneurysmal SAH; however, dural arteriovenous fistulae, particularly those with cortical venous drainage, appear to be at higher risk for early rebleeding [11,13].

Most brain vascular malformations that produce SAH are either arteriovenous malformations or dural arteriovenous fistulae. These are usually visualized on cerebral angiography [10,14,15]. Catheterization of the external carotid artery may be required to image intracranial dural arteriovenous malformations. Angiographically occult vascular malformations such as some cavernous malformations, developmental venous anomalies, and capillary telangiectasias are visualized on brain MRI, but are less likely to be a source of SAH.

Vascular malformations associated with bleeding are usually managed surgically and/or with endovascular interventions [16]. (See "Brain arteriovenous malformations" and "Vascular malformations of the central nervous system".)

Spinal — Spinal vascular malformations can also be a source of NASAH. Up to 10 percent of spinal vascular malformations present with SAH [9,17,18]. Dural arteriovenous fistulae are the most common type of spinal vascular malformation [19]. Those that cause SAH are usually, but not always, located in the cervical cord or craniocervical junction [20]. Prominent back or neck pain or myelopathic signs at presentation can indicate this source, but these are often absent and the clinical appearance can mimic that of intracranial aneurysm rupture [20-23].

Vascular malformations in the spine can be difficult to visualize on neuroimaging modalities [9,20,21]. Proximal vertebral artery angiography may reveal more rostral lesions. Often the diagnosis is delayed until the patient presents with recurrent SAH. These lesions are generally managed by neurosurgical and/or endovascular interventions. (See "Disorders affecting the spinal cord", section on 'Vascular malformations'.)

Intracranial arterial dissection — Dissection of an intracranial artery can produce SAH; in one case series, this accounted for 4.5 percent of SAH cases, but this high proportion likely reflects referral or case-ascertainment bias [24].

Dissection of an intracranial artery is usually initiated by a tear in the media producing an intramural hemorrhage that dissects longitudinally between the adventitia and media [25]. When the tear extends through (or is initiated in) the intima, a second, so-called false, lumen is created. Usually, this leads to narrowing of the lumen, thrombus formation, and thromboembolic stroke. However, if the dissection tears through the adventitia, an SAH occurs. The latter scenario is more common with vertebrobasilar dissections.

If SAH occurs, bleeding is massive and often devastating [24,26,27]. If patients survive the initial event, rebleeding occurs in 40 to 60 percent, often within the first 24 hours.

Many intracranial dissections are believed to occur in the setting of sudden or unusual stretching of arteries, but such a history is often lacking. While connective tissue diseases such as Ehler-Danlos syndrome type IV and fibromuscular dysplasia are associated with intracranial arterial dissection, most patients with dissection do not have these conditions. Migraine and hypertension may be risk factors. (See "Cerebral and cervical artery dissection: Clinical features and diagnosis", section on 'Associated conditions and risk factors'.)

Most cases of intracranial arterial dissection in the setting of SAH are diagnosed by conventional cerebral angiography [2,25,26]. MRI with fat saturation is also a sensitive test, demonstrating intramural blood on cross-sectional images [25].

Vertebrobasilar dissections may be treated surgically or with endovascular interventions, but data are limited (see "Cerebral and cervical artery dissection: Treatment and prognosis", section on 'Subarachnoid hemorrhage due to intracranial dissection'). Management is individualized according to location and other anatomic features, and can include ligation of the vertebral artery, trapping or wrapping of the pseudoaneurysm, bypass, and stenting. These are complicated procedures that can incur additional morbidity in these very sick patients.

Other causes

●Cerebral venous thrombosis can rarely present with SAH as its primary manifestation [6,28-32]. Usually the presentation is somewhat less abrupt than with aneurysmal rupture and the bleeding is localized and superficial. The thrombosis may be visualized on venous phase of digital subtraction angiography and/or on MRI. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

●Sickle cell disease can be complicated by subarachnoid as well as intracerebral hemorrhage [1,9,33]. Most reported cases occur in children with an established diagnosis. These children are often found to have one or more aneurysms; in some cases SAH is believed to result from fragile collateral blood vessels. Recent transfusion and treatment with corticosteroid therapy may be risk factors. Case fatality rate was as high as 34 percent in one report [33]. Survivors appear to have a low rate of recurrence. (See "Acute ischemic and hemorrhagic stroke in sickle cell disease", section on 'Intracranial hemorrhage - additional management'.)

●Bleeding disorders and anticoagulant therapy can be complicated by SAH, but this is a somewhat rare complication; intracerebral and subdural hemorrhages are more common [4,9,34-36]. Systemic bleeding usually accompanies the SAH if this is the primary cause; if it does not, the patient should be assumed to have an underlying aneurysm or other vascular lesion until proven otherwise. Similarly, analysis of one case series suggested that perimesencephalic NASAH can appear atypical, with more extensive hemorrhage, in the setting of reduced platelet activity [37]. However, this would be a diagnosis of exclusion as well. (See "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)

●Pituitary apoplexy often presents with sudden onset of headache and vomiting, and there can be prominent subarachnoid blood on CT scan, which may distract from or obscure the pituitary adenoma [38-41]. Pituitary apoplexy is usually heralded by vision change and is accompanied by extraocular nerve palsy. If not visualized on the initial CT scan, MRI will demonstrate the tumor [42,43]. Neurosurgical decompression is indicated for visual loss. Patients also require endocrine evaluation for potentially life-threatening, acute hypopituitarism. (See "Causes of hypopituitarism", section on 'Pituitary apoplexy'.)

●Traumatic SAH is usually identified by the clinical setting. However, if a clinical history is unavailable, radiologic clues of a traumatic origin include localized bleeding in superficial sulci, adjacent skull fracture, and cerebral contusion, as well as external evidence of traumatic injury [9,36]. Isolated SAH in the setting of mild traumatic brain injury (TBI; Glasgow Coma Scale [GCS] score ≥13) is typically associated with a benign neurologic outcome [44,45]. More severe TBI is typically associated with additional forms of brain injury (eg, intracerebral hemorrhage, diffuse axonal injury, etc). (See "Acute mild traumatic brain injury (concussion) in adults" and "Management of acute moderate and severe traumatic brain injury".)

●Cocaine abuse has been associated with both aneurysmal and nonaneurysmal SAH [6,9,46,47]. The mechanism of bleeding in the latter is not known, but may be related to acute blood pressure surges and/or an underlying hypertensive or toxic vasculopathy [9,48]. Patients with SAH and cocaine abuse should be assumed to have an underlying aneurysm or other vascular lesion until proven otherwise.

●Cerebral amyloid angiopathy can cause SAH in older adults. Bleeding is usually quite restricted, often to a single sulcus; microbleeds and/or superficial siderosis are often present on MRI [49-52]. (See "Cerebral amyloid angiopathy".)

●Rare causes of SAH include spinal aneurysms that can produce SAH, usually with prominent neck or back pain and myeloradicular symptoms [53,54].

Brain or cervical tumors have been reported to produce SAH as the presenting manifestation [6,55,56].

Moyamoya disease is associated with cerebral aneurysms that can rupture and produce SAH; rarely, SAH occurs due to rupture of the fragile transdural anastomotic vessels [57,58]. (See "Moyamoya disease: Etiology, clinical features, and diagnosis".)

SAH has also been reported with cerebral vasculitis, reversible cerebral vasoconstriction syndrome (RCVS), cerebral hyperperfusion syndrome after carotid endarterectomy, and also reversible posterior leukoencephalopathy syndrome [49,52,59-62]. (See "Overview of thunderclap headache", section on 'Reversible cerebral vasoconstriction syndromes' and "Reversible posterior leukoencephalopathy syndrome" and "Complications of carotid endarterectomy", section on 'Hyperperfusion syndrome'.)

CLINICAL PRESENTATION — The clinical presentation of NASAH often mimics that of aneurysmal SAH. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Clinical presentation'.)

However, the manifestations may differ, often depending on the underlying etiology (see 'Etiologies' above). In particular, restricted SAH over the convexity may manifest with transient motor or sensory symptoms that suggest epileptic phenomena and/or frank seizures [52].

DIAGNOSTIC EVALUATION — SAH should be considered in any patient complaining of a severe headache of sudden onset. Emergent CT of the head should immediately follow consideration of the diagnosis [36]. If the suspicion is high and the CT scan fails to show blood in subarachnoid space, a lumbar puncture must be obtained. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Evaluation and diagnosis'.)

A perimesencephalic pattern of blood on CT scan has a high probability of being nonaneurysmal in origin. (See "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)

Nontraumatic convexity SAH is associated with diverse group of etiologies that should be considered in the evaluation, including reversible cerebral vasoconstriction syndrome, cerebral amyloid angiopathy, posterior reversible encephalopathy syndrome, and cerebral venous thrombosis [63]. (See "Reversible cerebral vasoconstriction syndrome" and "Cerebral amyloid angiopathy" and "Reversible posterior leukoencephalopathy syndrome" and "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

Patients with SAH should undergo basic laboratory testing including complete blood count, serum chemistries, coagulation studies, and toxicology screen. A baseline electrocardiogram should also be obtained.

Cerebral angiography — Most vascular lesions responsible for SAH are identified using conventional digital subtraction cerebral angiography (DSA) that includes injections of the external carotid circulation and deep cervical branches, which may supply a cryptic dural arteriovenous fistula. Angiographic demonstration of key branch points, including the proximal posterior circulation, is essential to definitively rule out aneurysm. Proximal vertebral artery angiography may reveal a vascular malformation in the cervical spine or cranio-cervical junction. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis".)

The utility of CT angiography (CTA) is continuously improving [64]. A major advantage of CTA over conventional angiography is the speed and ease by which it can be obtained, often immediately after the diagnosis of SAH is made by head CT when the patient is still in the scanner. CTA is increasingly used as a first test in many patients with SAH, avoiding the need for conventional angiography in some patients [65-67]. In this setting, CTA is a more practical approach to acute diagnosis than magnetic resonance angiography (MRA), given the constraints of acute patient management. CTA has imperfect sensitivity for the detection of cerebral aneurysms, particularly small aneurysms [67]. Even when an aneurysm is identified by other technologies, DSA is often advocated to exclude multiple aneurysms and to better plan surgical intervention [68].

Repeat angiography — Up to 24 percent of all SAH patients with initial negative angiography have an aneurysm found on repeat angiography [1,6,7,9,14,69,70]. This may increase to as much as 49 percent if patients with perimesencephalic NASAH and patients with normal CT scans are excluded [1,7,71]. Repeat studies may also reveal an arterial dissection or a vascular malformation not identified on the initial study [20,21,72].

Therefore, it is critical to repeat DSA if the initial angiogram is negative. The appropriate timing of this study is unclear and probably should be individualized according to the patient's condition and presence of other complications. In reported case series, the repeat DSA has been performed between four days and four weeks [1,6,7,9,14,71,73-75]. Repeat DSA may not be necessary in patients who have an identified nonaneurysmal etiology of SAH and possibly in those with perimesencephalic SAH [3,7]. (See "Perimesencephalic nonaneurysmal subarachnoid hemorrhage", section on 'Repeated testing after technically inadequate initial study'.)

A third angiogram at a period of two to three months is advocated by some, but is probably not necessary in most patients [2,6,9,70,72]. If the prior studies are technically inadequate, or if rebleeding occurs, repeat angiography, if not surgical exploration, is warranted [2]. (See 'Further diagnostic study' below.)

Magnetic resonance imaging — MRI may demonstrate angiographically occult vascular lesions that can cause SAH. Such lesions include some vascular malformations in the brain or spinal cord; tumors, including pituitary adenoma; and arterial wall hematoma suggesting arterial dissection [23,76]. All patients with SAH and negative angiography should have gadolinium-enhanced MRI of the brain and spinal cord [6,19].

Further diagnostic study — Surgical exploration is not a routine aspect of the diagnostic evaluation, but is reported to lead to a diagnosis of ruptured aneurysm, even after two or more negative angiograms [2,6,77]. While in some cases this intervention was prompted by an episode of rebleeding or a suspicious but not diagnostic finding on angiography, it is not always certain in other cases why surgical exploration was performed.

Spinal angiography is also undertaken for diagnosis in some cases [20-23]. Usually this is prompted by a specific clinical suspicion for a spinal vascular anomaly such as prominent back or neck pain, radicular or myelopathic features on examination, or an abnormal but not diagnostic finding on other neuroimaging studies, such as MRI.

COMPLICATIONS — Common complications of SAH are:

●Rebleeding

●Vasospasm and cerebral ischemia

●Hydrocephalus

●Increased intracranial pressure

●Seizures

●Hyponatremia

●Cardiac abnormalities

There is little specific information about the incidence or severity of these complications in NASAH in comparison with aneurysmal SAH. Rebleeding risk is likely specific to the origin of SAH; this is discussed above under the individual etiologies. The risk of other complications, however, is expected to be somewhat similar across etiology.

The pathogenesis and clinical features of these complications are discussed separately. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Complications'.)

TREATMENT AND PROGNOSIS — The general care of patients with NASAH should be the same as aneurysmal SAH patients. In particular, those patients with diffuse SAH mimicking an intracranial aneurysm rupture on a CT scan may have a similarly complicated course that includes hydrocephalus and vasospasm, and therefore need to be carefully monitored [78]. Patients are admitted to an intensive care setting for constant hemodynamic and cardiac evaluation, given stool softeners, kept at bedrest, and given analgesia to diminish hemodynamic fluctuations and lower the risk of rebleeding. Pneumatic compression stockings to limit risk of deep vein thrombosis should be utilized while patients are immobile. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Critical care management'.)

Shunt-dependent hydrocephalus occurred in 14 percent of patients with NASAH in one retrospective series [79]. Associated risk factors included acute hydrocephalus, intraventricular hemorrhage, clinical vasospasm, and anticoagulation medication prior to SAH. Patients should receive other interventions to monitor, prevent, and treat complications of SAH. These are discussed separately. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Critical care management' and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Early complications' and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Vasospasm and delayed cerebral ischemia'.)

Patients with perimesencephalic SAH may be managed similarly to those with aneurysmal SAH until the presence of an aneurysm has been excluded. (See "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)

Interventions to prevent rebleeding and other etiologic-specific complications are individualized to the underlying etiology. (See 'Etiologies' above.)

In general, the prognosis for patients with NASAH are better than those with aneurysmal hemorrhage; however, NASAH represents a heterogenous group of patients and etiologies, and outcomes are largely dependent on the underlying cause and comorbidities [80,81].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Subarachnoid hemorrhage (The Basics)")

SUMMARY AND RECOMMENDATIONS — An estimated 15 to 20 percent of patients with subarachnoid hemorrhage (SAH) are nonaneurysmal. The causes of nonaneurysmal SAH (NASAH) are potentially diverse, and the mechanism of bleeding in these cases is often not identified.

●Perimesencephalic NASAH makes up the majority of NASAH in some case series. These have a distinctive appearance on CT and a benign course. (See "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".)

●Other causes of NASAH include occult aneurysm, intracranial or spinal vascular malformations, and intracranial arterial dissection. Less common etiologies include sickle cell disease, pituitary apoplexy, cocaine abuse, cerebral venous thrombosis, and bleeding disorders. (See 'Etiologies' above.)

●The diagnosis of SAH is usually made by CT of the brain, which should always be performed emergently in a patient with an abrupt onset of headache. A lumbar puncture should follow a negative CT scan if the clinical suspicion is high. (See 'Diagnostic evaluation' above.)

●All patients with SAH should be evaluated with basic laboratory testing including complete blood count, serum chemistries, and coagulation studies and toxicology screen. A baseline electrocardiogram should also be obtained. (See 'Diagnostic evaluation' above.)

●We recommend that conventional digital subtraction cerebral angiography (DSA) be performed in all patients with SAH, unless CT and/or CT angiography (CTA) adequately defines the pathogenesis. (See 'Cerebral angiography' above.)

●We recommend repeating DSA within 4 to 14 days after an initial negative study, because of the risk of a false negative. (See 'Repeat angiography' above.)

●Patients with negative angiography should undergo gadolinium-enhanced MRI of brain and spinal cord. (See 'Magnetic resonance imaging' above.)

●Some patients will not have an etiologic diagnosis after DSA and MRI. If rebleeding occurs in such patients, further diagnostic interventions may include further angiographic study of the brain and/or spinal cord, and/or surgical exploration. (See 'Further diagnostic study' above.)

●Complications of aneurysmal SAH, hydrocephalus, vasospasm and cerebral ischemia, seizures, hyponatremia, and cardiac abnormalities also occur in NASAH. In this regard, patients with NASAH should be managed similarly to aneurysmal SAH. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis".)

●Patients may also require interventions that are etiology specific. (See 'Etiologies' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David Brock, MD, CIP, who contributed to an earlier version of this topic review.