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, [3] granulomatous
angiitis
Genetic disorders: Marfan syndrome, Ehlers-Danlos syndrome, Osler-Weber-Rendu 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 [4]
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,[5] 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. [6] 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. [7]
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.