Subarachnoid hemorrhage

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space surrounding the brain, i.e., the area between the arachnoid membrane and the pia mater. It may arise due to trauma or spontaneously, and is a medical emergency which can lead to death or severe disability even if recognized and treated in an early stage. Treatment is with close observation, medication and early neurosurgical investigations and treatments. Subarachnoid hemorrhage causes 5% of all strokes. 10-15% die before arriving in hospital, and average survival is 50%.^[1]

Spontaneous SAH is most often due to rupture of cerebral aneurysms (85%), which are weaknesses in the wall of the arteries of the brain that enlarge. While most cases of SAH are due to bleeding from small aneurysms, there is evidence from research that larger aneurysms (which are rarer) are still more likely to rupture. A further 10% of cases is due to non-aneurysmal perimesencephalic hemorrhage, in which the blood is limited to the area of the midbrain. No aneurysms are generally found. The remaining 5% are due to vasculitic damage to arteries, other disorders affecting the vessels, disorders of the spinal cord blood vessels, and bleeding into various tumors.

Risk factors for subarachnoid hemorrhage are smoking, hypertension (high blood pressure) and excessive alcohol intake; all are associated with a doubled risk for SAH. Some protection of uncertain significance is conferred by Caucasian ethnicity, hormone replacement therapy, a higher than normal cholesterol and the presence of diabetes mellitus.^[2]

The classic symptom of subarachnoid hemorrhage is thunderclap headache (“most severe ever” headache developing over seconds to minutes). This headache is often described like being “kicked in the head”.^[3] 10% of all people with this symptom turn out to have a subarachnoid hemorrhage, and is the only symptom in about a third of all SAH patients. Other presenting features may be vomiting (non-specific), seizures (1 in 14) and meningism. Confusion, decreased level of consciousness or coma may be present. Intraocular hemorrhage (bleeding into the eyeball) may occur. Subhyaloid hemorrhages may be visible on fundoscopy (the hyaloid membrane envelopes the vitreous body).

A lumbar puncture (removal of cerebrospinal fluid/CSF with a needle from the lumbar sac under local anesthetic) will identify another 3% of the cases by demonstrating xanthochromia (yellow appearance of centrifugated fluid) or bilirubin (a breakdown product of hemoglobin) in the CSF.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Sara Mehrsefat, M.D. [3]

According to the etiology, spontaneous subarachnoid hemorrhage may be classified into traumatic, aneurysmal and nonaeurysmal subarachnoid hemorrhage.

According to the etiology, spontaneous subarachnoid hemorrhage may be classified into traumatic, aneurysmal and nonaeurysmal subarachnoid hemorrhage.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Ahsan Hussain, M.D.[2] Sara Mehrsefat, M.D. [3]

Subarachnoid hemorrhage (SAH) is the result of the bleeding within the subarachnoid space, which is filled with cerebrospinal fluid. It is a bleeding which is accumulated between the arachnoid and pia mater and can spread into intraventricular space, brain parenchyma and subdural space.^[1] Excluding head trauma, sub arachnid hemorrhage mainly results from spontaneous rupture of a saccular aneurysm.^[2] The exact pathogenesis of nonaneurysmal SAH (NASAH) is not fully understood. It is though that the mechanism of the bleeding in this type of subarachnoid hemorrhage is diverse. One of the most common subtype is called perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM NASAH). It is characterized as localized specific blood  pattern on computed tomography (CT), normal cerebral angiography, and less sever symptoms and course of the condition.^[3]

Subarachnoid hemorrhage (SAH) is the result of the bleeding within the subarachnoid space, which is filled with cerebrospinal fluid. It is a bleeding which is accumulated between the arachnoid and pia mater and can spread into intraventricular space, brain parenchyma and subdural space.^[1] Excluding head trauma, sub arachnid hemorrhage mainly results from spontaneous rupture of a saccular aneurysm.^[2]

Spontaneous subarachnoid hemorrhage can be a result of the aneurysmal rupture:^[1][2][4][5]

• Saccular aneurysms (responsible for most SAHs)
• Fusiform aneurysms (dilatation of the entire circumference of the vessel that may in part be formed due to atherosclerosis)
• Mycotic aneurysms  (infected emboli due to infective endocarditis)

Saccular (berry) aneurysms are responsible for most cases of subarachnoid hemorrhage (SAH). Multiple factors play a role in formation of a saccular aneurysms. Saccular aneurysms usually results from degenerative change in the vessel wall following:^[2]

• Hemodynamic stress (turbulent blood flow) which it may result in excessive tear and breakdown of the internal elastic lamina which it progress to lack of elastic lamina.

It is also thought that inflammatory process is also play a role in pathogenesis of aneurysms.^[4][6]

Common associated conditions may include:^[8][9][10]

• Hypertension
• Cigarette smoking
• Connective tissue disease
  • Ehlers-Danlos syndrome
  • Pseudoxanthoma elasticum
• Familial aldosteronism type I

The role for genetic factors in pathogenesis of aneurysmal formation has been approved. However, the exact pathogenesis remains unknown. It is thought that some connective tissue disease may result in arterial wall weakness and non-laminar flow pattern of blood, which is then progress to tear and breakdown of the wall.^[9][10] Additionally, it is thought concurrent hypertension may play a role in patient with autosomal dominant polycystic kidney disease (PKD).^[11]

It is thought that negative angiogram following subarachnoid hemorrhage can be observed in almost 25% of all cases. As a result even two negative angiograms result can not exclude aneurysmal subarachnoid hemorrhage.^[12][13][14]

Common reasons for having negative result in aSAH may include:^[12][14][15]

• Technical errors
• Hematoma
• Aneurysm thrombosis
• Vasospasm
• Small aneurysm size
• Aneurysm obscuration

Unruptured aneurysms wall may present with complete absence of endothelial lining.

However, ruptured aneurysm walls may present with Inflammatory cells (T cell and macrophage infiltration) in addition to complete absence of endothelial lining.

Histological types of aneurysm walls may be identified as follow:^[16]

The exact pathogenesis of nonaneurysmal SAH (NASAH) is not fully understood. It is though that the mechanism of the bleeding in this type of subarachnoid hemorrhage is diverse.

perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM NASAH) is characterized as localized specific blood  pattern on computed tomography (CT), normal cerebral angiography, and less sever symptoms and course of the condition.^[3][17][18]

The exact pathogenesis of perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM NASAH) is not fully understood. However the three possible hypothesis may be as following:^[17][19][20]

• Perforating artery disease:  Because of the specific location which PM NASAH occurs, rupture of perforating artery arising from the posterior circulation can be a possible theory.
• Venous source: Because of a low rate of rebleeding and low pressure bleeding, It is thought that PM NASAH happens in the setting of of venus leakage.
• Basilar artery abnormalities: It can be secondary to intramural hematoma or possible vasospasm

Possible associated conditions may include:^{[21][20][22][23]}

• Hypertension
• Acute lacunar infarctions
• Physical exertion

Spinal or intracranial vascular malformations may also result in subarachnoid hemorrhage. Instead of a brain parenchyma where normally vascular malformation occurs. Vascular lesion may also primarily occurs in the subarachnoid space and result in subarachnoid hemorrhage.^[24][25]

Vascular malformations may include:^{[24][25][26][27]}

• Arteriovenous malformation (AVM): Abnormal connection between arteries and veins in the brain and can result in vessels break and bleed into the brain.
• Dural arteriovenous fistulae

Dissection of an intracranial artery begins as a tear in the arterial wall. It is usually transverse and extends through the intima and halfway through the media and then create the false-lumen. In this setting, it usually result into thrombus formation, and thromboembolic stroke. If dissection extends through the adventitia, it may result in subarachnoid hemorrhage.^[24][28][29]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Ahsan Hussain, M.D.[2] Cafer Zorkun, M.D., Ph.D. [3]; Sara Mehrsefat, M.D. [4]

Subarachnoid hemorrhages may be caused by trauma or may occur spontaneously. Spontaneous SAH is most often due to rupture of cerebral aneurysms (85%), which are weaknesses in the wall of the arteries of the brain that enlarge. Beside aneurysmal rupture, other common causes of spontaneous subarachnoid hemorrhages include vascular events (such as arteriovenous malformation, dural arteriovenous fistula, perimesencephalic, Intracranial arterial dissection, and amyloid angiopathy), cerebral hyperperfusion syndrome after carotid endarterectomy, brain or cervical tumors, and illicit drug use (such as cocaine andamphetamines).^{[1][2][3][4][5][6][7][8]}

Subarachnoid hemorrhages may be caused by trauma or may occur spontaneously.

Common causes of subarachnoid hemorrhages include:^{[1][2][3][4][5][6][7][8][9]}

Head trauma following accident or a fall

Rupture of an aneurysm

• Saccular aneurysms (most common cause)
• Fusiform aneurysms
• Mycotic aneurysms

• Arteriovenous malformation
• Dural arteriovenous fistula
• Perimesencephalic
• Intracranial arterial dissection
• Amyloid angiopathy
• Cerebral venous thrombosis
• Cerebral vasculitis
• Reversible vasoconstriction syndrome

• Cocaine
• Amphetamines

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Ahsan Hussain, M.D.[2] Sara Mehrsefat, M.D. [3]

It is clinically difficult to distinguish subarchnoid hemorrhage from an ischemic stroke. However, the symptoms like headache, nausea, vomiting, and depressed level of consciousness should raise the suspicion for a hemorrhagic event compared to ischemic stroke.^[1][2]

Subarachnoid hemorrhage should be differentiated from other diseases causing severe headache for example: ^{[22][23][24][25][26][27][28][29][30][31]}

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

The incidence of subarachnoid hemorrhage was estimated 10.5 per 100 000 person annually.^[1] Subarachnoid hemorrhage (SAH) usually occurs at a relatively young age. the incidence of aneurysmal subarachnoid hemorrhage (aSAH) increases with age and commonly affects adults 􏰁≥50 years of age.^[2] females are slightly more affected with aneurysmal subarachnoid hemorrhage|subarachnoid hemorrhage (SAH) than men (1.24 times higher than in men).^[2][3]

• The incidence of subarachnoid hemorrhage was estimated 10.5 per 100 000 person annually.^[1]

• Subarachnoid hemorrhage (SAH) usually occurs at a relatively young age
• The incidence of aneurysmal subarachnoid hemorrhage (aSAH) increases with age and commonly affects adults 􏰁≥50 years of age.^[2]
• The mean age of perimesencephalic nonaneurysmal Subarachnoid hemorrhage|subarachnoid hemorrhage (PM-NASAH) occurrence was reported between 50 and 55 years.^[4]

• Women are slightly more affected with aneurysmal subarachnoid hemorrhage|subarachnoid hemorrhage (SAH) than men (1.24 times higher than in men).^[2][5]
• Unlike aneurysmal subarachnoid hemorrhage (SAH), the incidence of perimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-NASAH) does not vary by gender.^[4]

• The incidence of aneurysmal subarachnoid hemorrhage (aSAH is higher in Blacks and Hispanics compere to white Americans.^[6]

• In the United States, the incidence of aneurysmal subarachnoid hemorrhage (aSAH) is 10 to 15 cases per 100,000 population.^[7]
• In China, the incidence of aneurysmal aneurysmal subarachnoid hemorrhage (SAH) is 2 cases per 100,000 population.^[8]
• In South and Central America, the incidence of aneurysmal subarachnoid hemorrhage (aSAH) is 4 cases per 100,000 population.^[9]
• In Finland and Japan, the incidence of aneurysmal aneurysmal subarachnoid hemorrhage (SAH) is 19 to 23 cases per 100,000 population. ^[10]

• An average case fatality rate of subarachnoid hemorrhage (SAH) was estimated to be 50,000 cases per 100,000 individuals.^[11][12]
  • 10,000 cases per 100,000 individuals die prior reaching the hospital
  • 25,000 cases per 100,000 individuals die within 24 hours of SAH
  • 45,000 cases per 100,000 individuals die within 30 days of SAH

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Ahsan Hussain, M.D.[2] Cafer Zorkun, M.D., Ph.D. [3]; Sara Mehrsefat, M.D. [4]

Common risk factors in the development of subarachnoid hemorrhage include smoking, hypertension (high blood pressure) and excessive alcohol intake; all are associated with a doubled risk for SAH. Some protection of uncertain significance is conferred by Caucasian ethnicity, hormone replacement therapy, and a higher than normal cholesterol.^[1][2]

Common risk factors in the development of subarachnoid hemorrhage include: ^{[1][2][3][4][5][6][7][8][9][10]}

• Connective tissue diseases
  • Ehlers-Danlos syndrome
  • Pseudoxanthoma elasticum
• Familial hyperaldosteronism type I
• Autosomal dominant polycystic kidney disease (PKD)
• Moyamoya syndrome

• Arteriovenous malformation
• Head injury
• Hypertension
• Cigarette smoking
• Estrogen deficiency
• Female gender (1.5 fold)
• African race (2 fold)
• Japanese or Finnish descent
• Coarctation of the aorta
• Excessive alcohol intake
• Arteriovenous malformation

Common trigger events in the development of subarachnoid hemorrhage include:^[11][12][13]

• Physical exertion
• Acute elevation in blood pressure
• Caffeine consumption
• Acute anger
• Startling
• Sexual exertion

The highest incidence of rupture occurred while patients were engaged in their daily routines, in the absence of strenuous physical activity.^[14]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Sara Mehrsefat, M.D. [3]

Following rupture of an aneurysm, the blood directly release into the cerebrospinal fluid (CSF) under arterial pressure. As the blood spreads quickly into the CSF, it rapidly increasing intracranial pressure.^[1]  Increased intracranial pressure (ICP) occurs secondary to the following factors, including:^[2]

• Hemorrhage volume
• Acute hydrocephalus
• Reactive hyperemia after hemorrhage/ ischemia
• Distal cerebral arteriolar vasodilation

Depending on the location of the aneurysm, the blood can spread into:

• Intraventricular space
• Brain parenchyma
• Subdural space

The bleeding usually lasts only a few seconds. However, rebleeding can be considered as one of the complication which can occur within the first day.^[3]

Independent predictors of rebleeding after subarachnoid hemorrhage may include:^[4][5][6]

• Aneurysm size

• The Hunt-Hess grade on admission
• High bleeding pressure
• Presence of sentinel headache prior to SAH
• Early ventriculostomy
• High blood pressure prior to event

The vasospasm usually occurs following subarachnoid hemorrhage and typically begins no earlier than day three after hemorrhage and peak at days seven to eight. it is thought that the blood clots release a spasmogenic substances following blot clots lysis which can result in vasospasm. The vasospasm can lead to ischemia of the brain which is usually characterized as a single cortical infarcts near the site of the ruptured aneurysm in most case. ischemia of the brain usually results in neurologic deterioration in level of consciousness or new focal neurologic deficits.^[7][8]

Risk factors for developing vasospasm may include:^{[9][10] [11][12]}

• Severe bleeding
• Bleeding the major intracerebral blood vessels
• Age less than 50 years
• Hyperglycemia 

Complications of SAH can be acute, subacute, or chronic.

• Acute:^[13][14]
  • Coma and brainstem herniation due to increased intracranial pressure (ICP)
  • Rebleeding
  • Pulmonary edema (“neurogenic pulmonary edema”) as a result of the suddenly increased ICP
  • Cardiac arrhythmias and myocardial damage
  • Hydrocephalus, which may also happen in the subacute time frame
• Subacute:^[7][8][9]
  • Vasospasm, leading to ischemia of the brain
  • Hyponatremia (low sodium levels) – due to SIADH or cerebral salt wasting syndrome
• Chronic:
  • Long-term immobility
  • Pneumonia and pulmonary embolism (due to immobility)
  • SAH recurrence (20% within two weeks if the aneurysm is not secured by clipping or coiling)
  • Persistent neurologic deficits

Nearly half the cases of SAH are either dead or moribund before they reach a hospital. Of the remainder, a further 10-20% die in the early weeks in hospital from rebleeding. Delay in diagnosis of minor SAH without coma (or mistaking the sudden headache for migraine) contributes to this mortality. Patients who remain comatose or with persistent severe deficits have a poor prognosis.^[3]

Following conditions associated with poorer outcome:^{[15][16][17][18][19][20]}

• Seizures occur during the first 24 hours
• The combination of subarachnoid hemorrhage with preretinal hemorrhages (Terson’s syndrome)
• Rebleeding
• Renal dysfunction
• Fever
• Anemia
• Hypoxemia
• Metabolic acidosis
• Hyperglycemia
• Low or high blood pressure (MAP <70 or MAP >130 mmHg)

There are several grading scales available for subarachnoid hemorrhage. These have been derived by retrospectively matching characteristics of patients with their outcomes. In addition to the ubiquitously used Glasgow Coma Scale, three other specialized scores are in use.^[21][22]

The Hunt and Hess scale describes the severity of subarachnoid hemorrhage, and is used as a predictor of survival.^[23]

The Fisher Grade classifies the appearance of subarachnoid hemorrhage on CT scan. It is highly predictive of vasospasm^[24]

In assessing outcome of subarachnoid hemorrhage, the World Federation of Neurosurgeons classification recommended use of the Glasgow Coma Scale.^[25]

Ogilvy and Carter is a combination of clinical and radiological findings. It combined the patient age, Hunt and Hess and Fisher Scales as well as aneurysm size and location to create a new grading system and only surgically treated patients were included in the study.^[22]

One point is given for each of the following variables:

• Age greater than 50
• Hunt and Hess grade 4 to 5 (in coma)
• Fisher grade score 3 to 4
• Aneurysm size >10 mm
• An additional point is added for a giant posterior circulation aneurysm (≥25 mm)

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