Subarachnoid hemorrhage

The term subarachnoid hemorrhage (SAH) refers to extravasation of blood into the subarachnoid space between the pial and arachnoid membranes. It occurs in various clinical contexts, the most common being head trauma. However, the familiar use of the term SAH refers to nontraumatic (or spontaneous) hemorrhage, which usually occurs in the setting of a ruptured cerebral aneurysm or arteriovenous malformation (AVM). Essential update: Clinical and imaging clues to reversible cerebral vasoconstriction syndrome with subarachnoid hemorrhage Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches and reversible segmental multifocal cerebral artery narrowing, and it results in SAH in more than 30% of cases. Muehlschlegel and colleagues found that clinical and imaging findings can differentiate RCVS with SAH from other causes of SAH.[1, 2] After analyzing clinical and imaging features of 38 patients with RCVS-SAH, 515 patients with aneurysmal SAH, and 93 patients with cryptogenic (angiogram negative) SAH, Muehlschlegel et al identified clinical characteristics and radiological findings that can differentiate RCVS-SAH from aneurysmal SAH or cryptogenic SAH. These researchers concluded that these differences may be useful for improving diagnostic accuracy, clinical management, and resource utilization.[1, 2] Signs and symptoms Signs and symptoms of SAH range from subtle prodromal events to the classic presentation. The most common premonitory symptoms are as follows:

Headache (48%) Dizziness (10%) Orbital pain (7%) Diplopia (4%) Visual loss (4%)

Signs present before SAH include the following:

Sensory or motor disturbance (6%) Seizures (4%) Ptosis (3%)

Bruits (3%) Dysphasia (2%)

Prodromal signs and symptoms usually are the result of sentinel leaks, mass effect of aneurysm expansion, emboli, or some combination thereof. The classic presentation can include the following:

Sudden onset of severe headache (the classic feature) Accompanying nausea or vomiting Symptoms of meningeal irritation Photophobia and visual changes Focal neurologic deficits Sudden loss of consciousness at the ictus Seizures during the acute phase

Physical examination findings may be normal or may include the following:

Mild to moderate BP elevation Temperature elevation Tachycardia Papilledema Retinal hemorrhage Global or focal neurologic abnormalities

Complications of SAH include the following:

Hydrocephalus Rebleeding Vasospasm Seizures Cardiac dysfunction

See Clinical Presentation for more detail.

Diagnosis Diagnosis of SAH usually depends on a high index of clinical suspicion combined with radiologic confirmation via urgent noncontrast CT, followed by lumbar puncture or CT angiography of the brain. After the diagnosis is established, further imaging should be performed to characterize the source of the hemorrhage. Laboratory studies should include the following:

Serum chemistry panel Complete blood count Prothrombin time (PT)/activated partial thromboplastin time (aPTT) Blood typing/screening Cardiac enzymes Arterial blood gas (ABG) determination

Imaging studies that may be helpful include the following:

CT (noncontrast, contrast, or infusion) Digital subtraction cerebral angiography Multidetector CT angiography MRI (if no lesion is found on angiography) Magnetic resonance angiography (MRA; investigational for SAH)

Other diagnostic studies that may be warranted are as follows:

Baseline chest radiograph ECG on admission Lumbar puncture and CSF analysis

See Workup for more detail. Management Current treatment recommendations include the following:

Antihypertensive agents (eg, IV beta blockers) when mean arterial pressure exceeds 130 mm Hg Avoidance of nitrates (which elevate ICP) when feasible

Hydralazine and calcium channel blockers Angiotensin-converting enzyme (ACE) inhibitors (not first-line agents in acute SAH) In patients with signs of increased ICP or herniation, intubation and hyperventilation

Other interventions for increased ICP are as follows:

Osmotic agents (eg, mannitol) Loop diuretics (eg, furosemide) IV steroids (controversial but recommended by some)

Additional medical management is directed toward the following common complications:

Rebleeding Vasospasm Hydrocephalus Hyponatremia Seizures Pulmonary complications Cardiac complications

Surgical treatment to prevent rebleeding includes the following options:

Clipping the ruptured aneurysm Endovascular treatment[3] (ie, coiling)

The choice between coiling and clipping usually depends on the location of the lesion, the neck of the aneurysm, and the availability and experience of hospital staff. Screening is not recommended in the general population. However, it can lower cost and improve quality of life in patients at relatively high risk for aneurysm formation and rupture. See Treatment and Medication for more detail. Image library

A 47-year-old woman presented with headache and vomiting; her CT scan in the emergency department revealed subarachnoid hemorrhage. Next

Background
The term subarachnoid hemorrhage (SAH) refers to extravasation of blood into the subarachnoid space between the pial and arachnoid membranes. SAH constitutes half of all spontaneous atraumatic intracranial hemorrhages; the other half consists of bleeding that occurs within the brain parenchyma. Subarachnoid hemorrhage (see the image below) occurs in various clinical contexts, the most common being head trauma. However, the familiar use of the term SAH refers to nontraumatic (or spontaneous) hemorrhage, which usually occurs in the setting of a ruptured cerebral aneurysm or arteriovenous malformation (AVM).

CT scan reveals subarachnoid hemorrhage in the right sylvian fissure; no evidence of hydrocephalus is apparent. Intracranial saccular aneurysms (berry aneurysms) represent the most common etiology of nontraumatic SAH; about 80% of cases of SAH result from ruptured aneurysms. SAH is responsible for the death and/or disability of 18,000 persons each year in North America alone. In the United States, it is associated with an annual cost of $1.75 billion. Unfortunately, the difficulties in detecting unruptured aneurysms in asymptomatic patients practically preclude the possibility of preventing most instances of SAH.

About 6-8% of all strokes are caused by SAH from ruptured berry aneurysms. Over the past several decades, the incidence of other types of strokes has decreased; however, the incidence of SAH has not decreased. The history and physical examination, especially the neurologic examination, are essential components in the diagnosis and clinical staging of SAH (see Presentation). The diagnosis is confirmed radiologically via urgent computed tomography (CT) scan without contrast. Traditionally, a negative CT scan is followed with lumbar puncture. However, noncontrast CT followed by CT angiography (CTA) of the brain can rule out SAH with greater than 99% sensitivity.[4] (See Workup.) Current treatment recommendations involve management in an intensive care unit setting. The blood pressure is maintained with consideration of the patients neurologic status, and additional medical management is directed toward the prevention and treatment of complications. Surgical treatment to prevent rebleeding consists of clipping the ruptured berry aneurysm. Endovascular treatment [3] (ie, coiling) is an increasingly practiced alternative to surgical clipping (see Treatment). Previous Next

Pathophysiology
Aneurysms are acquired lesions related to hemodynamic stress on the arterial walls at bifurcation points and bends. Saccular or berry aneurysms are specific to the intracranial arteries because their walls lack an external elastic lamina and contain a very thin adventitiafactors that may predispose to the formation of aneurysms. An additional feature is that they lie unsupported in the subarachnoid space. Aneurysms usually occur in the terminal portion of the internal carotid artery and the branching sites on the large cerebral arteries in the anterior portion of the circle of Willis. The early precursors of aneurysms are small outpouchings through defects in the media of the arteries. These defects are thought to expand as a result of hydrostatic pressure from pulsatile blood flow and blood turbulence, which is greatest at the arterial bifurcations. A mature aneurysm has a paucity of media, replaced by connective tissue, and has diminished or absent elastic lamina. The probability of rupture is related to the tension on the aneurysm wall. The law of La Place states that tension is determined by the radius of the aneurysm and the pressure gradient across the wall of the aneurysm. Thus, the rate of rupture is directly related to the size of the aneurysm. Aneurysms with a diameter of 5 mm or less have a 2% risk of rupture, whereas 40% of those with a diameter of 6-10 mm have already ruptured upon diagnosis.

Although hypertension has been identified as a risk factor for aneurysm formation, the data with respect to rupture are conflicting. However, certain hypertensive states, such as those induced by use of cocaine and other stimulants, clearly promote aneurysm growth and rupture earlier than would be predicted by the available data. Brain injury from cerebral aneurysm formation can occur in the absence of rupture. Compressive forces can cause injury to local tissues and/or compromise of distal blood supply (mass effect). When an aneurysm ruptures, blood extravasates under arterial pressure into the subarachnoid space and quickly spreads through the cerebrospinal fluid around the brain and spinal cord. Blood released under high pressure may directly cause damage to local tissues. Blood extravasation causes a global increase in intracranial pressure (ICP). Meningeal irritation occurs. Rupture of AVMs can result in both intracerebral hemorrhage and SAH. Currently, no explanation can be provided for the observation that small AVMs (< 2.5 cm) rupture more frequently than large AVMs (>5 cm). In a 25-year autopsy study of 125 patients with ruptured or unruptured aneurysms conducted at Johns Hopkins, the following conditions correlated positively with the formation of saccular aneurysms:

Hypertension Cerebral atherosclerosis Vascular asymmetry in the circle of Willis Persistent headache Pregnancy-induced hypertension Long-term analgesic use Family history of stroke

The occurrence of aneurysms in children indicates the role of intrinsic vascular factors. A number of disease states resulting in weakness of the arterial wall are associated with an increased incidence of berry aneurysms. Mechanisms and disease states associated with higher incidence of berry aneurysms include the following:

Increased blood pressure: Fibromuscular dysplasia, polycystic kidney disease, aortic coarctation

Increased blood flow: Cerebral arteriovenous malformation (AVM); persistent carotid-basilar anastomosis; ligated, aplastic, or hypoplastic contralateral vessel Blood vessel disorders: Systemic lupus erythematosus (SLE), Moyamoya disease,[5] granulomatous angiitis Genetic disorders: Marfan syndrome, Ehlers-Danlos syndrome, Osler-WeberRendu syndrome, pseudoxanthoma elasticum, Klippel-Trenaunay-Weber syndrome Congenital conditions: Persistent fetal circulation, hypoplastic/absent arterial circulation Metastatic tumors to cerebral arteries: Atrial myxoma, choriocarcinoma, undifferentiated carcinoma Infections: Bacterial, fungal

Complications Complications of SAH include the following:

Hydrocephalus Rebleeding Delayed cerebral ischemia from vasospasm Intracerebral hemorrhage Intraventricular hemorrhage Left ventricular systolic dysfunction Subdural hematoma Seizures Increased intracranial pressure Myocardial infarction[6]

Hydrocephalus SAH can cause hydrocephalus by 2 mechanisms: obstruction of CSF pathways (ie, acute, obstructive, noncommunicating type) and blockage of arachnoid granulations by scarring (ie, delayed, nonobstructive, communicating type). Acute hydrocephalus is caused by compromise of CSF circulation pathways by interfering with CSF outflow

through the sylvian aqueduct, fourth ventricular outlet, basal cisterns, and subarachnoid space. CSF production and absorption rates are unaltered. Intraventricular blood is the strongest determinant for the development of acute hydrocephalus. Other risk factors include the following:

Bilateral ambient cisternal blood Increased age Vasospasm Use of antifibrinolytic drugs Intraventricular hemorrhage Left ventricular systolic dysfunction Subdural hematoma Seizures

Rebleeding Rebleeding of SAH occurs in 20% of patients in the first 2 weeks. The rebleeds in the first days ("blow out" hemorrhages) are thought to be related to the unstable nature of the aneurysmal thrombus, as opposed to lysis of the clot sitting over the rupture site. Clinical factors that increase the likelihood of rebleeding include hypertension, anxiety,[7] agitation, and seizures. Cerebral ischemia Delayed cerebral ischemia from arterial smooth muscle contraction is the most common cause of death and disability following aneurysmal SAH. Vasospasm can lead to impaired cerebral autoregulation and may progress to cerebral ischemia and infarction.[8] Most often, the terminal internal carotid artery or the proximal portions of the anterior and middle cerebral arteries are involved. The arterial territory involved is not related to the location of the ruptured aneurysm. Vasospasm is believed to be induced in areas of thick subarachnoid clot. The putative agent responsible for vasospasm is oxyhemoglobin, but its true etiology and pathogenesis remain to be elucidated. Intracerebral hemorrhage The mechanism of intracerebal hemorrhage (ICH) is direct rupture of aneurysm into the brain. ICH commonly results from internal cerebral artery (ICA), pericallosal, and anterior cerebral artery (ACA) aneurysms. Secondary rupture of a subarachnoid

hematoma into the brain parenchyma most commonly arises from middle cerebral artery aneurysms. Intraventricular hemorrhage Found in 13-28% of clinical cases of ruptured aneurysms and in 37-54% of autopsy cases, intraventricular hemorrhage (IVH) is a significant predictor of poor neurologic grade and outcome. Sources of IVH include the following:

Anterior cerebral artery (40%) Internal cerebral artery (25%) Middle cerebral artery (21%) Vertebrobasilar artery (14%)

Left ventricular systolic dysfunction LV systolic dysfunction in humans with SAH is associated with normal myocardial perfusion and abnormal sympathetic innervation. These findings may be explained by excessive release of norepinephrine from myocardial sympathetic nerves, which could damage both myocytes and nerve terminals.[9] Subdural hematoma Subdural hematoma (SDH) is rare following aneurysmal SAH, with reported incidence of 1.3-2.8% in clinical series and as high as 20% in autopsy series. The mechanisms of SDH involve tearing of arachnoid adherent to the dome of the aneurysm at the time of rupture, direct tearing of arachnoid by a jet of blood, and disruption of arachnoid by ICH, with secondary decompression of ICH into the subdural space. Increased intracranial pressure Elevations in ICP are due to mass effect of blood (subarachnoid, intracranial, intraventricular, or subdural hemorrhage) or acute hydrocephalus. Once ICP reaches mean arterial pressure (MAP), cerebral perfusion pressure becomes zero and cerebral blood flow stops, resulting in loss of consciousness and death. Previous Next

Etiology
Of nontraumatic subarachnoid hemorrhages, approximately 80% are due to a ruptured berry aneurysm. Rupture of arteriovenous malformations (AVMs) is the second most identifiable cause of SAH, accounting for 10% of cases of SAH. Most of the remaining cases result from rupture of the following types of pathologic entities:

Mycotic aneurysm Angioma Neoplasm Cortical thrombosis

SAH may reflect a secondary dissection of blood from an intraparenchymal hematoma (eg, bleeding from hypertension or neoplasm). Both congenital and acquired factors are thought to play a role in SAH. Evidence supporting the role of congenital causes in aneurysm formation includes the following:

Clusters of familial occurrence, such as in Finland, where the incidence of familial cerebral aneurysm is 10% Significant incidence of multiple aneurysms in patients with SAH (15%) The association of aneurysms with specific congenital diseases (eg, coarctation of the aorta, Marfan syndrome, Ehlers-Danlos syndrome, fibromuscular dysplasia, polycystic kidney disease)

Familial cases of AVM are rare, and the problem may result from sporadic abnormalities in embryologic development. AVMs are thought to occur in approximately 4-5% of the general population, of which 10-15% are symptomatic. Congenital defects in the muscle and elastic tissue of the arterial media in the vessels of the circle of Willis are found in approximately 80% of normal vessels at autopsy. These defects lead to microaneurysmal dilation (< 2 mm) in 20% of the population and larger dilation (>5 mm) and aneurysms in 5% of the population. Acquired factors thought to be associated with aneurysmal formation include the following:

Atherosclerosis Hypertension Advancing age Smoking Hemodynamic stress

Less common causes of SAH include the following:

Fusiform and mycotic aneurysms Fibromuscular dysplasia

Blood dyscrasias Moyamoya disease Infection Neoplasm Trauma (fracture at the base of the skull leading to internal carotid aneurysm) Amyloid angiopathy (especially in elderly people) Vasculitis

Risk factors Although risk factors for SAH have been evaluated extensively, little conclusive evidence has been derived. Smoking appears to be a significant risk factor, as does heavy alcohol consumption. The risk of AVM rupture is greater during pregnancy. Data regarding the relationship between hypertension and SAH are conflicting. Previously documented acute severe hypertension with diastolic pressure over 110 mm Hg has been linked to SAH. The following do not appear to be significant risk factors for SAH:

Use of oral contraceptives Hormone replacement therapy Hypercholesterolemia Vigorous physical activity