Cerebral Vasospasm After Subarachnoid Hemorrhage

Updated: Sep 12, 2022
Author: William W Ashley, Jr, MD, PhD, MBA; Chief Editor: Brian H Kopell, MD 


Practice Essentials

Cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is a well-described phenomenon that is defined as narrowing of the large and medium-sized intracranial arteries[1] ; most often, it affects the anterior circulation supplied by the internal carotid arteries. Cerebral vasospasm leading to delayed cerebral ischemia (DCI) continues to be a major complication and source of morbidity in cases of aSAH.[2]

As a consequence of the significant neurologic morbidity or mortality stemming from posthemorrhagic vasospasm, a great deal of interest and research has been focused on understanding its physiologic mechanism and developing effective preventive and therapeutic measures. However, the etiology of cerebral vasospasm remains poorly understood.

Management involves both prevention and active treatment.[3] No single therapeutic algorithm has shown to be uniformly effective in preventing vasospasm and its subsequent neurologic sequelae, though a number of therapeutic strategies have found to have varying degrees of utility.

The hemodynamic augmentation strategy known as triple-H therapy, which includes hypertension, hemodilution, and hypervolemia, has been an important component of treatment. Increases in mean arterial pressure (MAP) alone have been shown to be beneficial and have been achieved with various medications. Calcium-channel antagonists have been widely investigated for prevention of vasospasm in aSAH; nimodipine is currently recommended as first-line medical treatment for preventing post-aSAH cerebral vasospasm. 

More invasive means of treating vasospasm depend on the utilization of cerebral angiography and include intra-arterial vasodilator administration and balloon angioplasty. Guidelines have recommended these modalities as reasonable for treatment of symptomatic patients who are not responding to hypertensive therapy.


There are many postulated theories as to the etiology of cerebral vasospasm after aSAH, but the mechanisms ultimately responsible for vasospasm are still incompletely understood. There is evidence that the normal physiologic mechanisms and signaling molecules that regulate cerebral arterial diameter are altered.[4] The alteration of these regulatory processes results in excess cerebral arterial vasoconstriction. Molecules of interest in this regard include nitric oxide and endothelin.

Nitric oxide, a vasodilator produced by endothelial cells, helps maintain cerebral arterial dilation. There is some evidence that the breakdown products of red blood cells may be harmful to endothelial cells, and this harmful effect may compromise the ability of these cells to produce vasodilatory molecules such as nitric oxide.[1]  Endothelin, a vasoconstrictor,[5]  has been found to be elevated in cerebrospinal fluid (CSF) after aSAH and may play a role in cerebral vasospasm and DCI.[1, 6]

Research efforts are ongoing with the aim of further elucidating the mechanisms of vasospasm in the hope of developing better treatments.


Cerebral vasospasm has been estimated to occur in 12-30% of the approximately 30,000 North American patients who experience aSAH each year.[7, 8] It has been estimated that close to 50% of patients suffering from aSAH die before reaching medical care. Of those patients who are able to reach neurosurgical centers and have their aneurysm treated, an estimated 14% either die or sustain significant morbidity as a result of cerebral vasospasm.[8]

There are certain patient characteristics that may increase the likelihood of vasospasm occurring in a patient with aSAH. Some of the strongest predictors of vasospasm relate to the severity of the aSAH as graded according to several well-accepted classification systems. Both the Fisher Scale and the Hunt-Hess grading system have been shown to correlate with the incidence of vasospasm.

On the Fisher Scale, the thickness of the aSAH clot and the presence of intraventricular hemorrhage (IVH) are strong predictors of vasospasm.[9, 10] These are the primary determinants of the Modified Fisher Scale, with a higher Fisher score being directly correlated with the risk of vasospasm.[10]

The Hunt-Hess grade, which is determined primarily by clinical symptoms, is also strongly predictive of vasospasm. Hunt-Hess grade III-IV subarachnoid hemorrhages are associated with a much higher risk of subsequent severe vasospasm and DCI, but some postulate that this is only a proxy for the volume of subarachnoid blood present.[11] Other risk factors that have been associated with vasospasm are hypertension and cigarette smoking.[11]


The prognosis for patients suffering from cerebral vasospasm and DCI after aSAH is most closely related to the severity of the initial hemorrhage and the immediate clinical condition of the patient. These factors are closely linked to the risk of severe vasospasm.

One caveat to consider is that the degree of vasospasm, as assessed by angiography, is not always fully aligned with the clinical deterioration of the patient. There is evidence that some patients may develop severe vasospasm on angiography that is clinically silent, whereas other patients suffer devastating DCI and infarction but do not have the same degree of vasospasm on angiography. In general, patients suffering from vasospasm are at risk for ischemia causing cerebral infarction and thus permanent neurologic deficits.




Cerebral vasospasm occurs in the setting of recent aneurysmal subarachnoid hemorrhage (aSAH). Vasospasm most often presents within 3-7 days after aSAH but can occur at any time within the 21-day window following the initial hemorrhage. Vasospasm often causes delayed cerebral ischemia, which can present clinically in a number ways, depending on the severity of the vasospasm and on which intracranial vessels are most affected.

The most common presentation is neurologic deterioration manifested as decreased level of consciousness or onset of new focal neurologic deficits. Patients may complain of weakness, sensory changes, new or increasing headache, visual deficit, or other neurologic symptoms. In obtunded patients (eg, those with high-grade subarachnoid hemorrhage), cerebral vasospasm may be clinically silent. Diagnosis of cerebral vasospasm in these patients requires vigilance and regular radiologic surveillance (see Workup).

Physical Examination

Physical examination may reveal a constellation of signs and symptoms of ongoing vasospasm, depending on the severity of the condition and on which intracranial vessels are most affected.

Nonlocalizing symptoms include the following:

  • Lethargy
  • Disorientation
  • Meningismus
  • New or increasing headache

Focal neurologic deficits are related to the particular vessel involved, as follows:

  • Anterior cerebral artery (ACA) distribution - Disinhibition, confusion; mutism; lethargy, delayed responsiveness, abulia; leg weakness; with involvement of the recurrent artery of Heubner (a large ACA perforator), contralateral faciobrachial weakness without cortical findings
  • Middle cerebral artery (MCA) distribution - Hemiparesis, faciobrachial weakness, monoparesis; aphasia, apractagnosia; neglect
  • Posterior cerebral artery (PCA) distribution - Visual disturbance, hemianopsia

A diagnostic algorithm for post-aSAH cerebral vasospasm is depicted in the image below.

Diagnosis of cerebral vasospasm after aneurysmal s Diagnosis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.


The complications of cerebral vasospasm may consist of further clinical deterioration and poor neurologic outcome. Vasospasm leads to cerebral ischemia, and in severe cases, acute ischemic stroke from cerebral infarction can occur. This progression leads to irreversible neurologic deficits.

Neurologic outcomes can vary widely, depending on the unique circumstances of each patient. Focal deficits are likely to persist if the large intracranial arteries (eg, the ACA, MCA, and PCA) are severely affected by vasospasm. It has been estimated that approximately 7% of patients suffering severe vasospasm following aSAH will have permanent neurologic deficits, and another 7% will die.[8]



Diagnostic Considerations

Early diagnosis of vasospasm and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be challenging clinically.[12] There are many complications following aSAH that may cause a decreased level of consciousness or a new focal neurologic deficit.

Any cause of increased intracranial pressure (ICP), such as recurrent hemorrhage, hydrocephalus, or cerebral edema, can present similarly to vasospasm. Both obstructive and communicating hydrocephalus are common after aSAH, as are convulsive and nonconvulsive seizures, which have been seen in as many as 90% of aSAH patients and must be included in the differential diagnosis with a worsening or focal neurologic examination. Many of these diagnoses must be ruled out concomitantly before a definitive diagnosis of cerebral vasospasm is made.

Differential Diagnoses



Imaging Studies

Various imaging modalities are employed to diagnose cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). Currently, transcranial Doppler (TCD) is the primary imaging technique used in screening for asymptomatic spasm.[13, 14]  It is used both for diagnosis and for close monitoring.[3]

TCD is a noninvasive modality that extrapolates the likelihood of vasospasm on the basis of selective intracranial arterial blood flow velocity ratios, trends, and relations. It is less sensitive in some patients with unfavorable bony anatomy “windows” that hinder soft-tissue evaluation, and it is subject to user error or variability, which inevitably affects its clinical applicability.[15, 16]

Other imaging techniques routinely used in surveillance for vasospasm are computed tomography (CT) perfusion scanning[17] and conventional angiography, both of which have demonstrated efficacy with varying usage patterns and in different clinical settings. CT perfusion studies have been shown to be more useful for diagnosing vasospasm in patients with delayed neurologic deficits than they are in asymptomatic patients.[18, 16, 19, 20, 21]

Digital subtraction angiography (DSA) has been regarded as the gold standard for diagnosis and treatment of vasospasm, but outcome benefit for the treatment of angiographic vasospasm has not been demonstrated, leading to the addition of more qualitative blood flow tools.[16]

Magnetic resonance angiography (MRA) has been employed in this setting as well. In a study that compared three-dimensional (3D) spin-echo-based black-blood MRA (BBMRA) with time-of-flight (TOF)-MRA for detection of cerebral vasospasm in the early posttreament period after subarachnoid hemorrhage, Takano et al found that BBMRA, owing to its contrast properties, may be superior to TOF-MRA for the evaluation of intracranial arteries.[22]

New neurologic deficits caused by vasospasm may be difficult to recognize in patients who are already severely debilitated. For this reason, routine surveillance imaging studies are carried out to supplement the neurologic examination with the aim of diagnosing vasospasm before the onset of delayed cerebral ischemia (DCI). Common practice is as follows:

  • Routine TCD on a daily basis
  • Diagnostic cerebral angiography 1 week after aneurysm treatment
  • Adjunctive imaging as clinically indicated

Case example

A 26-year-old woman with a history of cocaine use presented with acute subarachnoid hemorrhage (Hunt-Hess grade III; Fischer grade III). (See the images below.) Cerebral angiography revealed an anterior communicating artery aneurysm. The aneurysm was treated successfully with surgical clipping. Five days after presentation, the patient became symptomatic as a consequence of cerebral vasospasm. Angiography demonstrated severe narrowing of the right anterior cerebral artery (ACA).

Initial presenting head CT scan showing subarachno Initial presenting head CT scan showing subarachnoid hemorrhage and blood filling basal cisterns.
Initial cerebral angiogram from patient with subar Initial cerebral angiogram from patient with subarachnoid hemorrhage.
Three-dimensional reconstruction of cerebral angio Three-dimensional reconstruction of cerebral angiogram showing anterior communicating artery aneurysm.
Follow-up head CT scan showing subarachnoid blood. Follow-up head CT scan showing subarachnoid blood.
Cerebral angiogram obtained on posthemorrhage day Cerebral angiogram obtained on posthemorrhage day 5 in patient symptomatic from vasospasm. Angiogram shows severe narrowing of right anterior cerebral artery.

Other Tests

In addition to clinical and radiographic evaluation for the prevention of DCI, alternative methods are being investigated, including continuous electroencephalography (EEG),[23, 24, 25] serum biomarker assays,[26] and bedside cerebral blood oxygenation monitoring.[27]



Medical Care

Although there is a paucity of class A evidence regarding prevention and treatment of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), a number of therapeutic strategies have been studied and found to have varying degrees of utility.[13]

Of the management options currently used, the hemodynamic augmentation strategy known as triple-H therapy, which includes hypertension, hemodilution, and hypervolemia, has been an important component. This approach was intended to improve cerebral perfusion by increasing mean arterial pressure (MAP) and reducing blood viscosity.[28]

One study found that approximately 70% of patients with vasospasm experienced improvement in their symptoms after initiation of triple-H therapy.[29] It must be kept in mind, however, that triple-H therapy can have significant complications, such as pulmonary edema and subsequent hypoxemia, which may be detrimental to an at-risk hypoperfused brain. A 2000 study by Lennihan et al found that hypervolemic therapy had no significant advantage over normovolemic therapy with respect to cerebral blood flow after subarachnoid hemorrhage and that the two therapies yielded similar incidences of symptomatic vasospasm.[30]

Increases in MAP alone have been shown to be beneficial to patients with vasospasm, and a number of medications have been investigated and utilized to achieve this goal.[31] Phenylephrine, norepinephrine, and dopamine are the primary pressors employed in this setting.[32, 33] Phenylephrine appears to have the most evidence to support its use; several trials have suggested that is effective in patients with preserved left ventricular function.[34, 35] Other medications, such as vasopressin, may play adjunctive roles to play in management.[36]

Calcium-channel antagonists have been widely investigated for prevention of vasospasm in aSAH.[37] In particular, nimodipine has been shown to improve neurologic outcomes after aSAH, but it does not decrease radiographic vasospasm and does not significantly reduce mortality.[38] Several studies have shown that nicardipine reduces vasospasm as determined by transcranial Doppler (TCD), but no clear improvements in outcome or mortality have been demonstrated.[39]

A myriad of other drugs, including magnesium oxide, antiplatelet agents, anti-inflammatory drugs, statins, and endothelin receptor antagonists, have been studied in attempts to exploit nuances of the many theories of vasospasm physiology, including inflammatory cascade, heme breakdown product–mediated oxidative injury, spreading depolarization, and potassium channel modulation, but there remains a need for data demonstrating clinical outcome benefit.[13, 40, 26, 41]

A review by Solar et al, which included six clinical articles and seven experimental articles using animal models of aSAH, found evidence to suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), especially coxibs, may be more effective than nimodipine in reducing post-aSAH vasospasm while yielding reducted mortality, improved functional outcome, and increased hypoaggregability.[42]  The authors noted, however, that at the time of publication, there had been only one randomized, double-blind, placebo-controlled trial showing a tendency toward a better outcome with a lower incidence of vasospasm or mortality.

A retrospective analysis by Jentzsch et al compared milrinone with nimodipine in 30 patients with aneurysmal SAH, angiographically confirmed cerebral vasospasm, and at least one intra-arterial pharmacologic angioplasty.[43]  The authors found intra-arterial nimodipine therapy to be superior to milrinone monotherapy. They suggested that nimodipine and milrinone may be used together in a complementary fashion within an escalation scheme (with nimodipine given first, complemented by milrinone in cases of severe vasospasm); they did not recommend milrinone monotherapy.

Shen et al carried out a systematic review and meta-analysis of 13 studies examining the efficacy of statins with respect to cerebral vasospasm, mortality, and DCI in patients with aSAH.[44]  The analysis included 776 patients who received statins and 821 who received placebo. Statin administration significantly reduced the frequency of vasospasm, delayed ischemic neurological deficit (DIND), vasospasm-DCI, and mortality but had insignificant efficacy in the prevention of disability, a neurologic poor prognosis, and creatine kinase/alanine aminotransferase/aspartate aminotransferase elevation.

In contrast to nimodipine, the endothelin receptor antagonist clazosentan was found to reduce angiographic spasm but to have no effect on outcome, as noted in the CONSCIOUS trials.[45, 46]

Nimodipine has been recommended as first-line medical treatment for preventing post-aSAH cerebral vasospasm. It is usually given orally at a dosage of 60 mg every 4 hours for 21 days after the initial subarachnoid hemorrhage.[13]  Maintenance of euvolemia and normal circulating blood volume is recommended to prevent vasospasm.[13] In symptomatic vasospasm, induction of hypertension is recommended to achieve increased cerebral blood flow.[13]  Hypervolemia is no longer recommended as a measure to prevent vasospasm.[13]  (See Guidelines.)

In a meta-analysis of five studies that included a total of 543 patients with aSAH, Saber et al found cilostazol, a selective inhibitor of phosphodiesterase 3, to be associated with decreased risks of symptomatic vasospasm, cerebral infarction, and poor outcome.[47] A large multicenter trial would be needed to confirm this association.

Surgical Care

More invasive means of treatment of vasospasm depend on the utilization of cerebral angiography. The most commonly employed methods have been the following:

  • Intra-arterial vasodilator administration
  • Balloon angioplasty

Papaverine was one of the drugs initially tried for intra-arterial injection, but it fell out of favor because of (1) the lack of evidence for its efficacy and (2) the possibility of serious side effects, including paradoxical vasospasm. Several studies suggested that intra-arterial verapamil may provide a benefit in terms of neurologic outcome but that the benefit may not be obtained via vasodilation.[41]

A retrospective study by Chen et al (N = 116) compared intra-arterial infusion of a single vasodilator (nicardipine or verapamil; n = 47) with intra-arterial infusion of a combination of nitroglycerin, verapamil, and nicardipine (n = 69) in patients with aSAH and cerebral vasospasm.[48] The multiple-agent regimen resulted in a 24.36% improvement in vessel diameter as compared with single-agent therapy and was associated with better functional outcome at discharge and at 90-day follow-up.

Angioplasty is an accepted modality for refractory vasospasm,[49] though there remains a need for more good-quality clinical data demonstrating its efficacy. Prophylactic angioplasty has not been demonstrated to yield any significant improvements in outcome.[50]

Guidelines have recommended intra-arterial vasodilator therapy and balloon angioplasty as reasonable treatment modalities in symptomatic patients who are not responding to hypertensive therapy.[13]  (See Guidelines and Table 1 below.)

Table 1. Recommendations for Endovascular Treatment of Cerebral Vasospasm (Open Table in a new window)

Degree of Radiographic Vasospasm

Clinical Findings

  Asymptomatic Symptomatic
Mild No intervention Vasodilation (rare)
Moderate Vasodilation Vasodilation ± balloon angioplasty
Severe Vasodilation ± balloon angioplasty (rare) Vasodilation + balloon angioplasty

A more recently developed approach to endovascular therapy for vasospasm involves mechanical dilation of vessels without obstruction of blood flow—for example, with the Comaneci device.[51, 52]  In February 2022, this device received a US Food and Drug Administration breakthough designation for treatment of cerebral vasospasm after hemorrhagic stroke.


Prevention of vasospasm after severe aSAH is challenging, in that vasospasm represents a natural progression of this disease process. Use of nimodipine continues to be recommended as a means to improve neurologic outcomes after aSAH, though it has not been shown to exert this effect by decreasing the incidence of vasospasm.[13]

Historically, strategies for preventing vasospasm emphasized triple-H therapy (hypervolemia, hemodilution, and hypertension). Systematic reviews of the literature have demonstrated that studies examining triple-H therapy have mostly been of poor design and quality. There is relatively little compelling evidence to supporting the use of triple-H therapy as an effective means of preventing vasospasm.[53, 54]

The American Heart Association (AHA) and the American Stroke Association (ASA) have stated that euvolemia should be the goal after aSAH and that induction of hypertension may be pursued once symptomatic vasospasm has been diagnosed.[13]  (See Guidelines.)



AHA/ASA Guidelines for Post-aSAH Cerebral Vasospasm

In 2012, the American Heart Association (AHA) and the American Stroke Association (ASA) published updated evidence-based guidelines on the comprehensive management of aneurysmal subarachnoid hemorrhage (aSAH), including the management of cerebral vasospasm and delayed cerebral ischemia (DCI).[13]  These guidelines were endorsed by the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, and the Society of NeuroInterventional Surgery.

The 2012 AHA/ASA recommendations for management of cerebral vasospasm and DCI after aSAH are as follows[13] :

  • Oral nimodipine should be administered to all patients with aSAH (class I; level of evidence, A) - It should be noted that this agent has been shown to improve neurologic outcomes but not cerebral vasospasm; the value of other calcium antagonists, whether administered orally or intravenously, remains uncertain
  • Maintenance of euvolemia and normal circulating blood volume is recommended to prevent DCI (class I; level of evidence, B) - Revised recommendation from previous guidelines
  • Prophylactic hypervolemia or balloon angioplasty before the development of angiographic spasm is not recommended(class III; level of evidence, B) - New recommendation
  • Transcranial Doppler is reasonable to monitor for the development of arterial vasospasm (class IIa; level of evidence, B) - New recommendation
  • Perfusion imaging with computed tomography (CT) or magnetic resonance imaging (MRI) can be useful to identify regions of potential brain ischemia (class IIa; level of evidence, B) - New recommendation
  • Induction of hypertension is recommended for patients with DCI unless blood pressure is elevated at baseline or cardiac status precludes it (class I; level of evidence, B) - Revised recommendation from previous guidelines
  • Cerebral angioplasty and/or selective intra-arterial vasodilator therapy is reasonable in patients with symptomatic cerebral vasospasm, particularly those who are not rapidly responding to hypertensive therapy (class IIa; level of evidence, B) -  Revised recommendation from previous guidelines


Calcium Channel Blockers

Nimodipine (Nimotop, Nymalize)