Acute Subarachnoid Hemorrhage

Etiology

About 85% of cases of nontraumatic SAH are secondary to a ruptured saccular aneurysm.[3] These aneurysms occur within the Circle of Willis and its branches. Other precipitators of SAH include illicit drug abuse (cocaine and amphetamines), occult trauma, arteriovenous malformations/fistulae, vasculitides, Intracranial arterial dissections, amyloid angiopathy, bleeding diathesis, sickle cell anemia, and anticoagulation disorders.[3] 

A family history of SAH increases the risk of SAH in individuals without any of these conditions. A study found that first-degree relatives of patients with SAH have a 3-to-5-fold increased risk of SAH compared with the general population. Unruptured aneurysms in families with cerebral aneurysms are more likely to rupture than those without a family history.[4] Patients with a family history of 2 or more first-degree relatives with aneurysmal SAH are recommended to undergo preventative screening.

A small proportion of aneurysmal SAH is known to have a genetic association. The genetic susceptibility appears to be heterogeneous, with multiple chromosomes implicated.[5][6][7][6] Some familial SAH pedigrees are most consistent with autosomal dominant inheritance, while others are most consistent with autosomal recessive or multifactorial transmission.[8][9] Inherited conditions associated with increased risk of cerebral aneurysm and SAH include autosomal dominant polycystic kidney disease, glucocorticoid-remediable aldosteronism, and Ehlers-Danlos syndrome. Autosomal dominant polycystic kidney disease is associated with cerebral aneurysms in up to 8% of patients.[3] Therefore, patients with autosomal dominant polycystic kidney disease also require screening if they have even 1 family member with a history of a ruptured aneurysm.[3]

Epidemiology

The incidence of spontaneous SAH is seen in about 1 per 10,000 people annually. Females are more commonly affected than males. Although this clinical entity is more common with older age, about 55% of patients with an SAH who present are under age 55.[10] Patients are at an increased risk of SAH if they have a history of smoking, hypertension, or excessive alcohol consumption.[11] 

Up to 10% of patients with an SAH report a history of bending over, lifting heavy objects, or performing other strenuous activities at the onset of their symptoms.[10] Hypertension, smoking, and family history are among the most common risk factors. Other risk factors include using sympathomimetic drugs, estrogen deficiency, and antithrombotic therapy. 

Pathophysiology

Saccular aneurysms account for most cases of SAH.[12] These intracranial aneurysms are thin-walled protrusions from an intracranial artery with a thin (or absent) tunica media and an absent internal elastic lamina.[12] Persistent hemodynamic stress leads to excessive wear on the wall of these arteries, causing turbulent blood flow within the vessel and leading to structural fatigue and aneurysm development.[12] Hypertension, cigarette smoking, and various connective tissue diseases can also contribute to arterial wall breakdown.[11] See Image. Diffuse SAH.

Fusiform aneurysms are caused by dilation of the entire circumference of the vessel, often formed due to atherosclerosis.[12] Mycotic (infected) aneurysms often result from emboli due to infective endocarditis.[12] However, these aneurysms are less likely to rupture than a saccular aneurysm.

Traumatic SAH

Traumatic SAH commonly occurs near the site of a skull fracture and intracerebral contusion. Radiologic clues of a traumatic origin include localized bleeding in a superficial sulcus, an adjacent skull fracture, and a cerebral contusion with external evidence of traumatic injury.[13]

Histopathology

Nontraumatic Subarachnoid Hemorrhage

Histopathologically, a nontraumatic SAH can be divided into 2 main types:

• Saccular aneurysm 
• Fusiform aneurysm
• Dolicoecthatic 

Depending on their shape, aneurysms are described as saccular, fusiform, or dolicoecthatic. Saccular aneurysms are pouch-or berry-like protrusions that arise from vascular bifurcations or the side of a vessel and often have an irregular shape with secondary protrusions. See Image. STAR Sign Subarachnoid Hemorrhage. Dilations or pathological increases in vessel caliber that do not lead to the forming of a separate saccular pouch are usually called fusiform aneurysms. In contrast, the tortuous, dilated elongations of vessels are called dolicoecthatic.

History and Physical

Patients presenting with an SAH classically present with a “thunderclap” headache (characterized as a severe headache that develops within seconds to minutes and has a maximal intensity at its onset), neck stiffness, vomiting, and decreased level of consciousness, hemiparesis, and occasionally, seizures.[2] The typical headache pattern is a pulsatile pain propagating toward the occiput.[2] Seizures are more common if an aneurysm causes the SAH, and an SAH in a patient with a history of seizures is often diagnostic of cerebral arteriovenous malformation.[2] Neck stiffness typically does not occur until about 6 hours after the onset of a SAH. Asymmetrical pupil size and loss of the pupillary light reflex may indicate brain herniation caused by rising intracranial pressure. Terson syndrome (vitreous hemorrhage resulting from a severe SAH) occurs in anywhere from 3% to 13% of cases.[2] Increased intracranial pressure can lead to a sympathetic surge due to the activation of the descending sympathetic nervous system at the medulla. This causes a local release of inflammatory mediators that activate the sympathetic system in the peripheral circulation.[14] This sympathetic surge may increase blood pressure, cardiac arrhythmias, and/or cardiac arrest.[14]

Electrocardiographic changes may include large U waves, T wave abnormalities, QT prolongation, Q waves, high R waves, cardiac dysthymias, and ST changes (elevation or depression).[14] Neurogenic pulmonary edema may occur if fluid from the pulmonary capillaries leaks into the alveoli due to increased pressure within the pulmonary circulation.[14] Patients may report a history of a head injury before the onset of symptoms or a known history of a cerebral aneurysm. Other risk factors include high blood pressure, smoking, family history, connective tissue disorders, and drug/alcohol abuse. Patients may also report having a history of a prior severe headache and/or a history of a small bleed with resolving symptoms within the past month. This is considered a sentinel bleed, which often precedes a more severe SAH. A headache from a sentinel bleed is extremely difficult to diagnose, as CT and LP can be unreliable in these cases.

Some physical exam findings include an oculomotor abnormality/palsy, which may indicate the posterior communicating artery as the source of the bleeding.[2] The patient may demonstrate neck stiffness on examination if there is meningeal irritation from the SAH.[2] In this case, the Kernig sign (inability to fully extend the knees when the thigh is flexed at the hip and knee is at 90-degree angles) and Brudinski sign (hip and knee flexion with passive neck flexion) may also be positive.[2]

Evaluation

Generally, a non-contrast head CT is obtained during the presentation.[15] Almost 99% of cases are picked up on head CT if performed within a 6-hour window.[15] However, MRI is considered more sensitive than head CT as time goes on.[1][16] However, If the non-contrast head CT is indeterminate or if the patient presents outside of the 6-hour window, a lumbar puncture (LP) is indicated.[17] Some studies have found lumbar puncture to show evidence of hemorrhage in 3% of patients with a normal head CT.[17] Conversely, a recent study concluded that LP, in their cohort of neurologically intact CT-negative emergency department headache patients, did not identify any cases of aneurysmal SAH but was associated with serious complications, a significant false-positive rate, and extended emergency department length of stay.[17] Thus, attempts to investigate SAH (or sentinel bleeds from a presumed small aneurysmal leak) with a CT scan and lumbar puncture should be discussed with patients in a shared decision-making approach with informed consent/refusal.

Regarding laboratory testing, consistently elevated red blood cell counts in all cerebrospinal fluid (CSF) tubes may indicate an SAH. By spectrophotometry or visual examination, the CSF can also be examined for xanthochromia (yellow appearance to the centrifugate fluid).[17] The presence of bilirubin within the CSF may also indicate an SAH; however, it takes a minimum of 12 hours for hemoglobin to be metabolized, so this method can only reliably detect an SAH 12 hours after its onset.[17] Lastly, cerebral angiography or CT angiography can help to identify an aneurysmal source of the bleeding.[17]

In 1968, Hunt and Hess established an SAH severity scale based on symptoms at presentation (see Image. Hunt and Hess Grading Scale).[18] The Fisher Grade was later created in 1980 to classify the SAH's appearance based on the CT scan's appearance.[18] In 1988, the World Federation of Neurosurgeons classification was developed to include the patient’s Glasgow coma score and focal neurological deficits to gauge symptom severity.[18] In 1998, Ogilvy and Carter created a comprehensive classification system to help predict outcomes and gauge therapy for patients with SAH.[19] Lastly, Claassen modified the Fisher Grade scale in 2001 to incorporate the additive risk from a concomitant intraventricular hemorrhage.[18]

Treatment / Management

Surgical correction of cerebral aneurysms was first introduced in the 1930s, and by the 1990s, coiling and clipping became popular as less-invasive treatment options for patients with SAH. The International Study of Unruptured Intracranial Aneurysms (ISUIA) has established prognostic data for patients with a history of a prior SAH or patients who were found to have an aneurysm as an incidental finding on brain imaging. They concluded that aneurysms smaller than 10 mm or an aneurysm that has never bled are unlikely to have a SAH and may not require surgical repair as a preventative measure.[20] The first step in managing an SAH is stabilizing the patient and getting an emergent neurosurgical evaluation.[17] Patients with a decreased Glasgow coma score may require intubation for airway protection.[21] Blood pressure, pulse, respiratory rate, and Glasgow coma score must frequently be monitored.[17] Pain control and antiemetics are often required for symptom control.[17](A1)

Once the diagnosis of an SAH is made, most patients are admitted to a neurosurgical intensive care unit, as up to 15% of these patients may have worsening bleeding during admission.[21][22] An external ventricular drain may be indicated if the patient has a poor clinical grade on admission, acute neurological deterioration, or progressive ventricular enlargement on CT.[21] This external ventricular drain may remove CSF or blood, which can cause increased intracranial pressure.[21]

Patients with a large hematoma, decreased level of consciousness, or any focal neurological deficits may require surgical removal of the blood and/or occlusion of the bleeding site.[17] If a cerebral aneurysm is identified on angiography, clipping or coiling can be used to reduce the risk of further bleeding. Clipping requires a craniotomy to visualize and place clips around the neck of the aneurysm. Coiling is an endovascular technique that locates and deploys coils within the aneurysm from a catheter inserted into the femoral artery.[23](A1)

Aneurysms of the middle cerebral artery tend to be amenable to clipping, whereas those of the basilar artery and posterior cerebral artery are typically more accessible by endovascular coiling.[23] The International Subarachnoid Aneurysm Trial demonstrated a better prognosis from the endovascular coiling of the anterior cerebral artery and anterior communicating artery aneurysms than clipping. However, coiling carries a slightly increased risk of aneurysm recurrence, so these patients are typically followed for several years with repeat angiography for monitoring purposes.[23] See Image. Multiple Intracranial Aneurysms. 

Early predictors of rebleeding include high systolic blood pressure, hematoma within the brain or ventricles, poor Hunt-Hess grade, posterior circulation aneurysms, and any aneurysms greater than 10 mm in size.[24] Systolic blood pressure should be below 140 to 160 mm Hg to prevent rebleeding.[17] Nicardipine is commonly used for this purpose.[17] Calcium channel blockers such as nimodipine or verapamil are often used to prevent vasospasm.[17] Vasospasm can lead to ischemic brain injury (delayed ischemia injury) due to the restricted blood flow caused by vessel constriction.[17] Delayed ischemia often presents with new neurological symptoms and is diagnosed with the help of transcranial Doppler. Cerebral angiography is used to confirm the diagnosis of DCI.[17] A blood flow velocity of more than 120 centimeters per second on transcranial Doppler suggests vasospasm.[25] Up to one-third of patients with SAH have vasospasm, and about half of these patients have permanent deficits as a result.[25] Nimodipine has been shown to improve patient outcomes if given between 4 and 21 days after bleeding from an aneurysmal SAH.[25] However, nimodipine has not been shown to affect long-term outcomes in traumatic SAH and is therefore not recommended in these cases.(A1)

Differential Diagnosis

The differential diagnosis for acute subarachnoid hemorrhage include the following:

• Meningoencephalitis
• Cluster headache
• Adult seizures
• Intracranial hemorrhage
• Ischemic cerebrovascular accident
• Migraine
• Transient ischemic attack

Prognosis

Unfortunately, SAH is often associated with poor outcomes.[26] Nearly half of patients presenting with an SAH caused by an underlying aneurysm die within 30 days, and a third of those who survive have complications. Roughly half of the patients with an SAH suffer from some neurocognitive impairment that impacts their quality of life.[27] Over 60% report ongoing and recurring headaches.[27]

Complications

Cerebral vasospasm typically occurs after the third day of onset and typically peaks on the fifth to the seventh day.[28][25] Blood products released from the SAH stimulate the tyrosine kinase pathway, which results in smooth muscle contraction of the cerebral arteries, leading to vasospasm.[28] If vasospasm does occur, it is treated with intravenous fluids to achieve a state of hypertension, hypervolemia, and hemodilution.[28] This triad is often called “Triple H.”[28]. However, no randomized controlled trials have been conducted to support its utility. If vasospasm continues despite this medical management, angiography may be attempted to identify the site of spasms and administer intra-arterial vasodilator medication (ie, verapamil) or angioplasty with balloon stenting.[28]

Other reported complications of SAH include hydrocephalus, hypopituitarism, cardiac decompensation, fluctuations in blood pressure and electrolyte levels, and seizures.[29][30] It has been reported that seizures occur in up to a third of SAH hospitalizations.[26][23] Although antiepileptic drugs are often given to prevent seizure occurrence, research has yet to show any benefit from their administration.[26] Some studies have suggested a worse prognosis and increased risk of gastric hemorrhage associated with these medications, but the etiology of these findings remains unclear.[26]