Subarachnoid Hemorrhage (SAH)

Introduction

Subarachnoid hemorrhage (SAH) occurs when blood leaks into the fluid-filled spaces that surround the brain and its blood vessels. The two most common causes of SAH are trauma to the head and rupture of an intracranial aneurysm. An aneurysm is a localized widening or dilation of an artery that fills with blood and can rupture; aneurysms may occur in any blood vessel in the body, but the focus of this review will be on intracranial (brain) aneurysms which may lead to SAH if they rupture (Figure 1).

 

Figure 1: Angiogram images of a large aneurysm located at the tip of the basilar artery.

 

        SAH is considered a type of stroke(ischemic stroke knol) and accounts for 5% of all strokes in the United States. Non-traumatic SAH carries a high mortality and morbidity; 10% of patients die prior to reaching the hospital and less than 50% can return to their previous level of functioning following SAH. Each year, 30,000 cases of SAH occur in the United States¹. Since SAH affects a younger population of patients compared with other types of stroke, it leads to a proportionally larger number of life years lost and a higher total morbidity, with an estimated aggregate cost of $5 billion annually. 

Risk Factors for SAH

Since nearly 85% of non-traumatic SAH is caused by ruptured aneurysms, risk factors for development of aneurysms and risk factors for SAH overlap substantially. Women have a 1.6 times greater risk of SAH than men, and nonwhites have higher rates of SAH than Caucasians. Smoking, hypertension, and heavy alcohol use are the three most important modifiable risk factors for SAH². Taking antiplatelet (such as aspirin) or anticoagulant medications (such as warfarin) to thin the blood likely does not increase the risk of SAH, but when an SAH occurs, these medicines may make the bleeding and subsequent severity of the illness worse. A close family history of SAH also increases the risk, and multiple studies have identified genetic risk factors for aneurysm development and rupture. Many of these identified genes regulate proteins involved in maintaining the structural integrity of the blood vessel wall. Some rare specific genetic syndromes such as the connective tissue disease Ehlers-Danlos syndrome and autosomal dominant polycystic kidney disease (ADPKD) have been associated with a greater risk of aneurysm formation and SAH in addition to their systemic manifestations.

Locations of Cerebral Aneurysms

Intracranial aneurysms that lead to SAH typically occur at branch points of intracranial blood vessels near the Circle of Willis, a ring of connected blood vessels that supply the majority of the cerebral circulation (Figure 2). Common locations include the anterior communicating artery, the posterior communicating artery, the bifurcation of the middle cerebral artery, and the basilar artery. About 20-30% of patients with one cerebral aneurysm will have at least one other aneurysm. Once one aneurysm has ruptured in a patient, each of the patient’s other aneurysms should be treated due to their high risk of rupture.

 

Figure 2: Cartoon of the Circle of Willis. 

 

 

 

 

 

 

 

 

 

From:
http://www.nlm.nih.gov/medlineplus/ency/imagepages/18009.htm

Diagnosis of Subarachnoid Hemorrhage

The classic clinical presentation of SAH is the sudden onset of the worst headache of a patient’s life. Unlike more benign headache syndromes such as migraine, the hallmark SAH headache reaches maximal intensity over seconds to minutes. The abrupt nature of headache onset has been characterized as “thunderclap” in nature. Other symptoms that may occur at the time of aneurysm rupture include loss of consciousness, confusion, seizure, nausea, vomiting, and focal neurologic deficits. Many of these signs are indicative of the rapid rise in intracranial pressure (ICP) which may accompany SAH. Because blood in the subarachnoid space often leads to inflammation of the meninges that surround the brain, stiff neck and photophobia (sensitivity to light) may accompany SAH as in infectious meningitis. From one-third to one-half of patients with SAH will have experienced a milder sudden onset headache in the days to weeks preceding the hemorrhage; these warning headaches are likely “sentinel bleeds” in which the aneurysm leaks a small amount of blood prior to a larger rupture.

The diagnosis of SAH should be considered in all patients who present to medical attention with the sudden onset of a new or severe headache. SAH is a neurologic emergency and prompt recognition and treatment is essential in order to improve the chances of a good outcome. Non-contrast computed tomography (CT) scanning of the brain is the first step in the evaluation of suspected SAH (Figure 3). If the scan is performed within 12-24 hours after the hemorrhage, modern third-generation CT scanners can detect the presence of subarachnoid blood in 92-100% of cases. However, after the first day and with smaller amounts of hemorrhage, SAH can be missed with CT alone; therefore a lumbar puncture (“spinal tap”) must be performed in all patients with suspected SAH whose CT scan is normal. An elevated number of red blood cells that do not clear with successive tubes of CSF is the hallmark of SAH within the first 6 hours after rupture; after this time window, a yellowish tint to the fluid termed xanthochromia, which signifies the breakdown of blood products, is diagnostic of SAH and remains present in the spinal fluid for up to 2 weeks following hemorrhage. Magnetic resonance imaging (MRI) scans of the brain have been studied recently for the diagnosis of SAH and seem to compare favorably to CT. However, a negative MRI, like CT, in a patient with suspected SAH still necessitates a lumbar puncture to exclude the diagnosis.

 

Figure 3: Non-contrast CT scan of the brain demonstrating subarachnoid hemorrhage (SAH) in a patient with the sudden onset of a severe headache and stiff neck 1 hour prior to this scan.

 

            After SAH has been diagnosed, the next step is to investigate the underlying etiology. Since ruptured intracranial aneurysms account for 85% of all non-traumatic SAH, a careful search for aneurysm is the next step in management. The gold standard for identification of cerebral aneurysms remains catheter-based cerebral angiography. Since the hemorrhage may rarely obscure the aneurysm on initial angiography, it is important to repeat the angiogram (usually a few days to a few weeks later) in cases where the initial angiogram does not identify a source of SAH. Non-invasive imaging studies such as CT Angiography (CTA) and MR Angiography (MRA) are becoming increasingly popular and can identify most proximal aneurysms larger than 5 millimeters with reasonable accuracy.

Up to 15% of non-traumatic SAH is non-aneurysmal in nature. These patients tend to have a more favorable prognosis and a lower risk of recurrence. Approximately 10% of patients with SAH do not have an aneurysm and show a pattern of blood on CT primarily surrounding the brainstem. These so-called “perimesencephalic” hemorrhages carry a benign prognosis, low recurrence, and may be caused by a venous rather than arterial bleeding source. Other non-aneurysmal sources of SAH include arterial dissection, drug abuse (including cocaine and amphetamines), vascular malformations such as arteriovenous malformations (AVMs), and coagulopathy.

To allow physicians to communicate with families and each other regarding the severity of SAH, a number of scales have been developed to grade SAH; high grade patients have worse outcomes and more complications compared to those with lower grades. The Hunt and Hess scale is probably the most widely used scale and was developed primarily to assess surgical risk (see Table 1). Although the Hunt and Hess scale is very easy to administer, it has been criticized for its lack of reproducibility. The World Federation of Neurologic Surgeons (WFNS) scale was developed to improve the reliability of the Hunt and Hess scale, but studies have shown conflicting data as to whether it has accomplished this goal. Finally, the Fisher scale was developed to assess the risk of vasospasm (the constriction of a blood vessel to the brain) following SAH, using only information obtained from the amount and pattern of blood seen on the initial CT scan.

 

TABLE 1: The Hunt and Hess scale for assessing subarachnoid hemorrhage (SAH)  

Grade   Description of Patient

1              Asymptomatic or mild headache and slight nuchal rigidity

2              Severe headache, stiff neck, no neurologic deficit except cranial nerve palsy

3              Drowsy or confused, mild focal neurologic deficit

4              Stuporous, moderate or severe hemiparesis

5              Coma, decerebrate posturing

*A proposed modification adds a Grade 0 for unruptured aneurysms and Grade 1a for fixed neurologic deficit alone

Initial Management of SAH

SAH is a neurologic emergency and should be treated as such since life-threatening complications can occur in the hours and days following hemorrhage. Patients with SAH should be admitted to an intensive care unit (ICU), where frequent monitoring of neurologic, cardiac, and respiratory status can occur. It is recommended that all anticoagulant and antiplatelet medications be discontinued and that anticoagulant effects be reversed rapidly with Vitamin K, fresh frozen plasma (FFP), or solutions of clotting factors such as prothrombin complex concentrate³.

High blood pressure is common following SAH and can lead to the devastating complication of re-rupture of an aneurysm that has not yet been secured. Lowering the blood pressure has not definitively been shown to reduce the rate of re-rupture, although most believe that it may. Lowering the blood pressure of an SAH patient acutely is not without risks. In the setting of high ICP, a rapid drop in blood pressure could theoretically reduce perfusion pressure to the brain and result in secondary ischemia to vital tissues. Most centers begin by treating pain, nausea, and anxiety in an attempt to lower blood pressure. If the pressure remains elevated, short acting intravenous blood pressure agents are used to achieve a modest decrease in systemic blood pressure.

Patients with SAH are at risk for acute hydrocephalus as the absorption of normally clear CSF is impaired by blood in the subarachnoid space. Acute hydrocephalus can present as a sudden or gradual deterioration in the level of alertness, often with accompanying increased headache, nausea, and vomiting. Hydrocephalus can be definitively diagnosed with a non-contrast head CT. Placing a ventriculostomy, which allows CSF to drain externally, is often life-saving. The ventriculostomy (also termed an external ventricular drain, [EVD]) not only drains CSF but also functions as an ICP monitor, providing valuable dynamic information to physicians that can influence treatment. While some patients will be able to wean off of the ventriculostomy during the course of their hospitalization, others may require a permanent internal shunt to be placed that allows for drainage of CSF, usually into the abdominal cavity (ventriculoperitoneal shunt, [VPS]).

Patients with aneurysmal SAH should all receive the calcium channel blocking drug nimodipine. This drug was initially designed to prevent vasospasm in SAH but likely improves outcomes in SAH through other mechanisms which are not completely understood. A recent meta-analysis of multiple studies of nimodipine demonstrated that the drug reduces the chances of a poor outcome and decreases secondary ischemic events when given within the first few days after SAH⁴.

Some patients with SAH will present with seizures. These patients should be treated with anti-seizure drugs in order to prevent further spells. Administration of anti-seizure medications on a prophylactic basis in patients with SAH who have not experienced a first seizure remains controversial. There is mounting evidence that exposure to anti-epileptic drugs in SAH patients may actually lead to worse outcomes and more complications⁵. As a result, some centers only use these drugs if the patient presents with a clinical seizure and do not use them on a preventative basis.

Treatment of the Aneurysm

Once a patient has been stabilized, the ruptured aneurysm must be treated (“secured”) in order to prevent further rupture. Most aneurysms are treated soon after SAH (in the first 24-72 hours) given the high risk of recurrent hemorrhage. Two techniques to secure aneurysms, surgical clipping and endovascular coiling, are widely practiced, and there remains substantial controversy as to which technique is best suited for aneurysms that can be successfully treated by both methods.

Surgical clipping involves a neurosurgical procedure to remove part of the skull (“craniotomy”) so that the aneurysm can be directly visualized by the surgeon. Placing a clip across the neck of the aneurysm prevents further aneurysm rupture and growth because blood no longer will flow through the aneurysm (Figure 4). Aneurysm clipping surgeries have greater success rates with fewer complications in the hands of surgeons and centers that perform the procedure more frequently⁶.

 

 

Figure 4: Intraoperative surgical images of a large intracranial aneurysm (A) successfully treated by placing an aneurysm clip around the neck of the aneurysm (B). Courtesy of Michael T. Lawton, MD.

 

            An alternative to clipping is endovascular coiling, in which platinum coils are used to pack the aneurysm, obliterating the aneurysm via thrombus (clot) formation around the coils (Figure 5). The technique is much less invasive, using only a single puncture in the femoral artery in the groin to achieve access to the cerebral vasculature similar to a routine angiogram. A microcatheter is advanced to the aneurysm site so that coils may be deployed. Again it appears that interventionalists (radiologists, neurosurgeons, and neurologists) who perform this procedure more frequently have better outcomes with fewer complications.

 

Figure 5: Pre-treatment (left) and post-treatment (right) angiogram images of a ruptured aneurysm near the origin of the posterior cerebral artery treated successfully with endovascular coiling. The coils are visible, filling the aneurysm on the post-treatment image.

 

            A large, randomized study of over 2100 patients, the International Subarachnoid Aneurysm Trial (ISAT), demonstrated that for aneurysms that were judged to be treatable through either procedure, those patients treated with endovascular coiling had a survival benefit that has extended to at least 7-year follow up, providing some data that endovascular coiling may be the preferred technique⁷. It remains to be seen if endovascular coiling will prove as effective as clipping with follow-up periods greater than 10 years.

The ISAT trial included mainly aneurysms in patients with low grade SAH that were located in the anterior circulation; the results may not be able to be generalized to all aneurysm locations and to all SAH patients. In addition, the ISAT trial included only aneurysms that the treating physicians felt could be treated successfully with either modality. Many SAH patients have aneurysm characteristics that clearly favor one approach over another. Patients with aneurysms in distal locations, those that are very large, and those with a wide neck are best treated with surgical clipping. Endovascular coiling is preferred in patients with a poor clinical grade, those who are older with other co-existing medical conditions, and for aneurysms that are located in certain areas with higher surgical risk such as the tip of the basilar artery.

The decision regarding appropriate treatment modality should be made with each individual patient. Ideally, institutions would have expertise in treating aneurysms with both techniques, and a multidisciplinary approach would be utilized where the treating physicians from all specialties use patient-specific information to help patients and their families select the most appropriate therapy. 

Complications of SAH and Their Management

Patients who survive the initial hemorrhage and undergo successful aneurysm clipping or coiling are still at risk for multiple complications that can lead to substantial morbidity. Each of these complications can occur in the first 2 weeks following SAH and each tends to be more frequent in patients with higher grade SAH.

Vasospasm

Nearly one-half of patients with SAH will experience some degree of vasospasm, with approximately one-quarter of patients becoming symptomatic. Vasospasm is a focal narrowing of the cerebral blood vessels that occurs secondary to blood being deposited in the subarachnoid space (Figure 6). Vasospasm can lead to cerebral infarction (stroke) when a vascular territory is deprived of blood flow due to severe narrowing of arteries.

 Figure 6: Carotid angiogram demonstrating severe narrowing of cerebral blood vessels due to vasospasm 6 days following Hunt and Hess grade IV SAH.

             

            Management of all SAH patients involves careful monitoring for development of vasospasm. Vasospasm typically begins in the first 3-5 days following hemorrhage, peaks around day 7-10, and resolves over 2-3 weeks. The risk of vasospasm development is higher with increasing grade of SAH, a higher volume of blood surrounding the Circle of Willis on initial CT scan, and in younger patients.

The clinical neurologic examination is the most useful tool for monitoring the patient for the development of vasospasm. Any new neurologic deficit, including new weakness, numbness, or increased confusion in a patient with SAH should be considered a manifestation of vasospasm until proven otherwise. Transcranial Doppler (TCD) examination, an ultrasound-based test that measures how fast blood is flowing through the cerebral vessels, allows for direct detection of vasospasm occurring in the proximal blood vessels of most patients⁸. The gold standard for vasospasm detection is conventional catheter-based angiography, although the sensitivity of this technique can lead to identification of mild vasospasm that is perhaps not clinically relevant. Because angiography is invasive, other modalities such as TCD and CTA are often first used to screen for vasospasm.

Medical treatment of vasospasm includes the use of so-called “triple H” therapy where hypertension (increasing the blood pressure), hypervolemia (increasing the amount of intravenous fluids), and hemodilution (decreasing the blood count) can be used to improve flow through the narrowed segments of blood vessels. In practice, most centers only use hypertension and hypervolemia because lower blood counts (hemodilution) may actually increase ischemia in injured areas of the brain. Although the triple H approach is widely used, there is little systematic evidence that proves its efficacy⁹.

In patients who are refractory to medical therapy, a variety of endovascular techniques are used to treat vasospasm using conventional angiography. Vessels that are severely narrowed can be treated either with angioplasty, where a balloon is used to open the vessel, or with local arterial infusions of various vasodilatory medications such as verapamil or papaverine.

Hyponatremia

Patients with SAH may develop severe decreases in their serum sodium levels (hyponatremia) in a time course that roughly parallels that of vasospasm. Although controversy remains as to the exact mechanism of this electrolyte problem in these patients, it is often termed “cerebral salt wasting” because some unknown factor released after SAH causes the kidneys to lose salt at a sometimes drastic rate. Low sodium levels can increase cerebral edema and may cause devastating further injury after SAH. Patients should have their sodium levels monitored frequently and replacement should occur, if needed, with oral sodium tablets or intravenous hypertonic saline solutions. Fluid restriction is not recommended as dehydration may worsen vasospasm and lead to secondary ischemia. Most cases of hyponatremia in SAH will resolve within 2-3 weeks of the hemorrhage.

Neurocardiogenic Effects

Patients with SAH are also at risk for lung and cardiac injury following their hemorrhage due to incompletely characterized substances that are released systemically when the subarachnoid space fills with blood. Neurocardiogenic effects may include heart failure, simulating massive myocardial infarction (MI). Unlike the more typical MI, these cardiac changes are usually reversible, although aggressive cardiac support may be needed through the acute period. The development of neurogenic pulmonary edema often requires mechanical ventilatory support and may be secondary to heart failure or due to alternative mechanisms. These neurocardiogenic complications are rarer than vasospasm, hydrocephalus, or hyponatremia and usually resolve within the first 7-10 days after hemorrhage. Prompt recognition and treatment of these complications may be life-saving in SAH patients.

Unruptured Intracranial Aneurysms

Unruptured, asymptomatic aneurysms are often found incidentally when brain imaging with CT or MRI is performed for unrelated reasons¹⁰. An unruptured aneurysm is present in between 2-5% of all individuals. Since SAH is a relatively rare condition, affecting about 30,000 patients each year, it can be concluded that most aneurysms will not rupture. When an incidental aneurysm is discovered, a careful discussion regarding the risks and benefits of prophylactic aneurysm treatment must occur.

Not all aneurysms carry the same risk of rupture. The large International Study of Unruptured Intracranial Aneurysms (ISUIA) study provided important information as to the natural history of these aneurysms, with a mean follow-up of four years¹¹. Increased rates of rupture were associated with larger size (greater than 7mm in diameter) and location in the posterior circulation. Age did not substantially impact the yearly rate of rupture in this study, but older age has been associated with a greater risk of complications following aneurysm treatment. It is likely reasonable to conservatively manage small (less than 7mm) aneurysms, especially those located in the anterior circulation. If the patient does decide to treat an unruptured aneurysm, then a careful weighing of the risks of clipping or endovascular coiling needs to take place. Some centers follow unruptured aneurysms with serial imaging studies and then decide to intervene only if there appears to be aneurysm growth over time; little evidence exists to support this approach. Modeling aneurysms with MR-based techniques to predict rates of growth and risk of rupture is an active area of research.

Aneurysm Screening in Patients with a Family History

Having a close family member with an aneurysmal SAH is an important SAH risk factor. The lifetime risk of SAH in a patient with only one family member with SAH is fairly similar to the general population and screening for aneurysms in these patients is not recommended¹². However, in patients where two or more affected first degree relatives have aneurysms, screening should be offered as their risk of aneurysm formation is between 2-7 times greater than the general population¹³. Many families with multiple affected members have as yet undefined genetic tendencies to aneurysm formation. The best modality for aneurysm screening in these patients remains unclear. Most advocate using a non-invasive modality such as MRA or CTA. Whether to repeat the imaging study at some interval if the initial screen is negative, looking for development of new aneurysms, remains a source of debate.

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USEFUL WEBSITES

http://www.strokecenter.org/pat/sah.htm

http://www.bafound.org/info/subarachnoid.php