Nontraumatic intraparenchymal hemorrhage most commonly results from hypertensive damage to blood vessel walls e.g.:

- hypertension

- eclampsia

- drug abuse,

but it also may be due to autoregulatory dysfunction with excessive cerebral blood flow e.g.:

- reperfusion injury

- hemorrhagic transformation

- cold exposure

- rupture of an aneurysm or arteriovenous malformation (AVM)

- arteriopathy (e.g. cerebral amyloid angiopathy, moyamoya)

- altered hemostasis (e.g. thrombolysis, anticoagulation, bleeding diathesis)

- hemorrhagic necrosis (e.g. tumor, infection)

- venous outflow obstruction (e.g. cerebral venous sinus thrombosis).

Nonpenetrating and penetrating cranial trauma can also be common causes of intracerebral hemorrhage.

Acquired cerebrovascular diseases are those that are obtained throughout a person's life that may be preventable by controlling risk factors. The incidence of cerebrovascular disease increases as an individual ages. Causes of acquired cerebrovascular disease include atherosclerosis, embolism, aneurysms, and arterial dissections. Atherosclerosis leads to narrowing of blood vessels and less perfusion to the brain, and it also increases the risk of thrombosis, or a blockage of an artery, within the brain. Major modifiable risk factors for atherosclerosis include:

Controlling these risk factors can reduce the incidence of atherosclerosis and stroke. Atrial fibrillation is also a major risk factor for strokes. Atrial fibrillation causes blood clots to form within the heart, which may travel to the arteries within the brain and cause an embolism. The embolism prevents blood flow to the brain, which leads to a stroke.

An aneurysm is an abnormal bulging of small sections of arteries, which increases the risk of artery rupture. Intracranial aneurysms are a leading cause of subarachnoid hemorrhage, or bleeding around the brain within the subarachnoid space. There are various hereditary disorders associated with intracranial aneurysms, such as Ehlers-Danlos syndrome, autosomal dominant polycystic kidney disease, and familial hyperaldosteronism type I. However, individuals without these disorders may also obtain aneurysms. The American Heart Association and American Stroke Association recommend controlling modifiable risk factors including smoking and hypertension.

Arterial dissections are tears of the internal lining of arteries, often associated with trauma. Dissections within the carotid arteries or vertebral arteries may compromise blood flow to the brain due to thrombosis, and dissections increase the risk of vessel rupture.

Prognostics factors:

Lower Glasgow coma scale score, higher pulse rate, higher respiratory rate and lower arterial oxygen saturation level is prognostic features of in-hospital mortality rate in acute ischemic stroke.

Diseases associated with cerebral atherosclerosis include:

- Hypertensive arteriopathy

This pathological process involves the thickening and damage of arteriole walls. It mainly affects the ends of the arterioles which are located in the deep gray nuclei and deep white matter of the brain. It is thought that this is what causes cerebral microbleeds in deep brain regions. This small vessel damage can also reduce the clearance of amyloid-β, thereby increasing the likelihood of CAA.

Diseases cerebral atherosclerosis and associated diseases can cause are:

- Alzheimer's disease

Alzheimer's disease is a form of dementia that entails brain atrophy. Cerebral amyloid angiopathy is found in 90% of the cases at autopsy, with 25% being severe CAA.

- Cerebral microbleeds (CMB)

Cerebral microbleeds have been observed during recent studies on dementia sufferers using MRI.

- Stroke

Strokes occur from the sudden loss of blood flow to an area of the brain. The loss of flow is generally either from a blockage or hemorrhage. Studies of postmortem stroke cases have shown that intracranial athreosclerotic plaque build up occurred in over half of the individuals and over one third of the overall cases had stenotic build up.

Asymptomatic individuals with intracranial stenosis are typically told to take over the counter platelet inhibitors like aspirin whereas those with symptomatic presentation are prescribed anti-coagulation medications. For asymptomatic persons the idea is to stop the buildup of plaque from continuing. They are not experiencing symptoms; however if more build up occurs it is likely they will. For symptomatic individuals it is necessary to try and reduce the amount of stenosis. The anti-coagulation medications reduce the likelihood of further buildup while also trying to break down the current build up on the surface without an embolism forming. For those with severe stenosis that are at risk for impending stroke endovascular treatment is used. Depending on the individual and the location of the stenosis there are multiple treatments that can be undertaken. These include angioplasty, stent insertion, or bypass the blocked area.

Although there is a lack of robust studies demonstrating the efficacy of lifestyle changes in preventing TIA, many medical professionals recommend them. These include:

- Avoiding smoking

- Cutting down on fats to help reduce the amount of plaque build up

- Eating a healthy diet including plenty of fruits and vegetables

- Limiting sodium in the diet, thereby reducing blood pressure

- Exercising regularly

- Moderating intake of alcohol, stimulants, sympathomimetics, etc.

- Maintaining a healthy weight

In addition, it is important to control any underlying medical conditions that may increase the risk of stroke or TIA, including:

- Hypertension

- High cholesterol

- Diabetes mellitus

- Atrial fibrillation

In younger patients, vascular malformations, specifically AVMs and cavernous angiomas are more common causes for hemorrhage. In addition, venous malformations are associated with hemorrhage.

In the elderly population, amyloid angiopathy is associated with cerebral infarcts as well as hemorrhage in superficial locations, rather than deep white matter or basal ganglia. These are usually described as "lobar". These bleedings are not associated with systemic amyloidosis.

Hemorrhagic neoplasms are more complex, heterogeneous bleeds often with associated edema. These hemorrhages are related to tumor necrosis, vascular invasion and neovascularity. Glioblastomas are the most common primary malignancies to hemorrhage while thyroid, renal cell carcinoma, melanoma, and lung cancer are the most common causes of hemorrhage from metastatic disease.

Other causes of intraparenchymal hemorrhage include hemorrhagic transformation of infarction which is usually in a classic vascular distribution and is seen in approximately 24 to 48 hours following the ischemic event. This hemorrhage rarely extends into the ventricular system.

By definition, TIAs are transient, self-resolving, and do not cause permanent impairment. However, they are associated with an increased risk of subsequent ischemic strokes, which can be permanently disabling. Therefore, management centers around the prevention of future ischemic strokes and addressing any modifiable risk factors. The optimal regimen depends on the underlying cause of the TIA.

It is estimated that lacunar infarcts account for 25% of all ischemic strokes, with an annual incidence of approximately 15 per 100,000 people. They may be more frequent in men and in people of African, Mexican, and Hong Kong Chinese descent.

Major risk factors for cerebral infarction are generally the same as for atherosclerosis: high blood pressure, Diabetes mellitus, tobacco smoking, obesity, and dyslipidemia. The American Heart Association/American Stroke Association (AHA/ASA) recommends controlling these risk factors in order to prevent stroke. The AHA/ASA guidelines also provide information on how to prevent stroke if someone has more specific concerns, such as Sickle-cell disease or pregnancy. It is also possible to calculate the risk of stroke in the next decade based on information gathered through the Framingham Heart Study.

In an ischemic stroke, blood supply to part of the brain is decreased, leading to dysfunction of the brain tissue in that area. There are four reasons why this might happen:

1. Thrombosis (obstruction of a blood vessel by a blood clot forming locally)

2. Embolism (obstruction due to an embolus from elsewhere in the body, see below),

3. Systemic hypoperfusion (general decrease in blood supply, e.g., in shock)

4. Venous thrombosis.

Stroke without an obvious explanation is termed "cryptogenic" (of unknown origin); this constitutes 30-40% of all ischemic strokes.

Hemodynamic impairment is thought to be the cause of deep watershed infarcts, characterized by a rosary-like pattern. However new studies have shown that microembolism might also contribute to the development of deep watershed infarcts. The dual contribution of hemodynamic impairment and microembolism would result in different treatment for patients with these specific infarcts.

A sharp drop in blood pressure is the most frequent cause of watershed infarcts. The most frequent location for a watershed stroke is the region between the anterior cerebral artery and middle cerebral artery. These events caused by hypotension do not usually cause the blood vessel to rupture.

The main risk is intracranial hemorrhage. This risk is difficult to quantify since many patients with asymptomatic AVMs will never come to medical attention. Small AVMs tend to bleed more often than do larger ones, the opposite of cerebral aneurysms. If a rupture or bleeding incident occurs, the blood may penetrate either into the brain tissue (cerebral hemorrhage) or into the subarachnoid space, which is located between the sheaths (meninges) surrounding the brain (subarachnoid hemorrhage). Bleeding may also extend into the ventricular system (intraventricular hemorrhage). Cerebral hemorrhage appears to be most common.

One long-term study (mean follow up greater than 20 years) of over 150 symptomatic AVMs (either presenting with bleeding or seizures) found the risk of cerebral hemorrhage to be approximately 4% per year, slightly higher than the 2-3% seen in other studies. A simple, rough approximation of a patient's lifetime bleeding risk is 105 - (patient age in years), assuming a 3% bleed risk annually. For example, a healthy 30-year-old patient would have approximately a 75% lifetime risk of at least one bleeding event. Ruptured AVMs are a significant source or morbidity and mortality; post rupture, as many as 29% of patients will die, and only 55% will be able to live independently.

70% of patients with carotid arterial dissection are between the ages of 35 and 50, with a mean age of 47 years.

No randomized, controlled clinical trial has established a survival benefit for treating patients (either with open surgery or radiosurgery) with AVMs that have not yet bled.

Brain ischemia has been linked to a variety of diseases or abnormalities. Individuals with sickle cell anemia, compressed blood vessels, ventricular tachycardia, plaque buildup in the arteries, blood clots, extremely low blood pressure as a result of heart attack, and congenital heart defects have a higher predisposition to brain ischemia in comparison their healthy counterparts.

Sickle cell anemia may cause brain ischemia associated with the irregularly shaped blood cells. Sickle shaped blood cells clot more easily than normal blood cells, impeding blood flow to the brain.

Compression of blood vessels may also lead to brain ischemia, by blocking the arteries that carry oxygen to the brain. Tumors are one cause of blood vessel compression.

Ventricular tachycardia represents a series of irregular heartbeats that may cause the heart to completely shut down resulting in cessation of oxygen flow. Further, irregular heartbeats may result in formation of blood clots, thus leading to oxygen deprivation to all organs.

Blockage of arteries due to plaque buildup may also result in ischemia. Even a small amount of plaque build up can result in the narrowing of passageways, causing that area to become more prone to blood clots. Large blood clots can also cause ischemia by blocking blood flow.

A heart attack can also cause brain ischemia due to the correlation that exists between heart attack and low blood pressure. Extremely low blood pressure usually represents the inadequate oxygenation of tissues. Untreated heart attacks may slow blood flow enough that blood may start to clot and prevent the flow of blood to the brain or other major organs. Extremely low blood pressure can also result from drug overdose and reactions to drugs. Therefore, brain ischemia can result from events other than heart attacks.

Congenital heart defects may also cause brain ischemia due to the lack of appropriate artery formation and connection. People with congenital heart defects may also be prone to blood clots.

Other events that may result in brain ischemia include cardiorespiratory arrest, stroke, and severe irreversible brain damage.

Recently, Moyamoya disease has also been identified as a potential cause for brain ischemia. Moyamoya disease is an extremely rare cerebrovascular condition that limits blood circulation to the brain, consequently leading to oxygen deprivation.

The prognosis for pediatric stroke survivors varies. The following are some common outcomes:

- Cerebral Palsy (often Hemiplegic Cerebral Palsy/Hemiplegia)

- Epilepsy

- Vision Loss

- Hearing Loss

Therapeutic hypothermia has been attempted to improve results post brain ischemia . This procedure was suggested to be beneficial based on its effects post cardiac arrest. Evidence supporting the use of therapeutic hypothermia after brain ischemia, however, is limited.

A closely related disease to brain ischemia is brain hypoxia. Brain hypoxia is the condition in which there is a decrease in the oxygen supply to the brain even in the presence of adequate blood flow. If hypoxia lasts for long periods of time, coma, seizures, and even brain death may occur. Symptoms of brain hypoxia are similar to ischemia and include inattentiveness, poor judgment, memory loss, and a decrease in motor coordination. Potential causes of brain hypoxia are suffocation, carbon monoxide poisoning, severe anemia, and use of drugs such as cocaine and other amphetamines. Other causes associated with brain hypoxia include drowning, strangling, choking, cardiac arrest, head trauma, and complications during general anesthesia. Treatment strategies for brain hypoxia vary depending on the original cause of injury, primary and/or secondary.

About 10% of cases of moyamoya disease are familial, and some cases result from specific genetic mutations. Susceptibility to moyamoya disease-2 (MYMY2; 607151) is caused by variation in the RNF213 gene (613768) on chromosome 17q25. Moyamoya disease-5 (MYMY5; 614042) is caused by mutation in the ACTA2 gene (102620) on chromosome 10q23.3; and moyamoya disease-6 with achalasia (MYMY6; 615750) is caused by mutation in the GUCY1A3 gene (139396) on chromosome 4q32. Loci for the disorder have been mapped to chromosome 3p (MYMY1) and chromosome 8q23 (MYMY3; 608796). See also MYMY4 (300845), an X-linked recessive syndromic disorder characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism. and linked to q25.3, on chromosome 17". (Online Mendelian Inheritance in Man, omim.org/entry/252350).

In Japan the overall incidence is higher (0.35 per 100,000). In North America, women in the third or fourth decade of life are most often affected, but the condition may also occur during infancy or childhood. These women frequently experience transient ischaemic attacks (TIA), cerebral hemorrhage, or may not experience any symptoms at all. They have a higher risk of recurrent stroke and may be experiencing a distinct underlying pathophysiology compared to patients from Japan.

Moyamoya disease can be either congenital or acquired. Patients with Down syndrome, sickle cell anemia, neurofibromatosis type 1, congenital heart disease, fibromuscular dysplasia, activated protein C resistance, or head trauma can develop moyamoya malformations. It is more common in women than in men, although about a third of those affected are male.

According to a review of 51 studies from 21 countries, the average incidence of subarachnoid hemorrhage is 9.1 per 100,000 annually. Studies from Japan and Finland show higher rates in those countries (22.7 and 19.7, respectively), for reasons that are not entirely understood. South and Central America, in contrast, have a rate of 4.2 per 100,000 on average.

Although the group of people at risk for SAH is younger than the population usually affected by stroke, the risk still increases with age. Young people are much less likely than middle-age people (risk ratio 0.1, or 10 percent) to have a subarachnoid hemorrhage. The risk continues to rise with age and is 60 percent higher in the very elderly (over 85) than in those between 45 and 55. Risk of SAH is about 25 percent higher in women over 55 compared to men the same age, probably reflecting the hormonal changes that result from the menopause, such as a decrease in estrogen levels.

Genetics may play a role in a person's disposition to SAH; risk is increased three- to fivefold in first-degree relatives of people having had a subarachnoid hemorrhage. However, lifestyle factors are more important in determining overall risk. These risk factors are smoking, hypertension (high blood pressure), and excessive alcohol consumption. Having smoked in the past confers a doubled risk of SAH compared to those who have never smoked. Some protection of uncertain significance is conferred by caucasian ethnicity, hormone replacement therapy, and diabetes mellitus. There is likely an inverse relationship between total serum cholesterol and the risk of non-traumatic SAH, though confirmation of this association is hindered by a lack of studies. Approximately 4 percent of aneurysmal bleeds occur after sexual intercourse and 10 percent of people with SAH are bending over or lifting heavy objects at the onset of their symptoms.

Overall, about 1 percent of all people have one or more cerebral aneurysms. Most of these, however, are small and unlikely to rupture.

Diabetes mellitus increases the risk of stroke by 2 to 3 times. While intensive blood sugar control has been shown to reduce small blood vessel complications such as kidney damage and damage to the retina of the eye it has not been shown to reduce large blood vessel complications such as stroke.

Recent investigations have established that both moyamoya disease and arteriovenous fistulas (AVFs) of the lining of the brain, the dura, are associated with dural angiogenesis. These factors may represent a mechanism for ischemia contributing to the formation of dural AVFs. At least one case of simultaneous unilateral moyamoya syndrome and ipsilateral dural arteriovenous fistula has been reported at the Barrow Neurological Institute. In this case a 44-year-old man presented with headache, tinnitus, and an intraventricular hemorrhage, as seen on computed tomographic scans. Cerebral angiography showed a right moyamoya pattern and an ipsilateral dural AVF fed by branches of the external carotid artery and draining into the transverse sinus. This extremely rare coincidental presentation may have deeper pathogenic implications.

Nutrition, specifically the Mediterranean-style diet, has the potential for decreasing the risk of having a stroke by more than half. It does not appear that lowering levels of homocysteine with folic acid affects the risk of stroke.

One cause of microangiopathy is long-term diabetes mellitus. In this case, high blood glucose levels cause the endothelial cells lining the blood vessels to take in more glucose than normal (these cells do not depend on insulin). They then form more glycoproteins on their surface than normal, and also cause the basement membrane in the vessel wall to grow abnormally thicker and weaker. Therefore they bleed, leak protein, and slow the flow of blood through the body. As a result, some organs and tissues do not get enough blood (carrying oxygen & nutrients) and are damaged, for example, the retina (diabetic retinopathy) or kidney (diabetic nephropathy). Nerves and neurons, if not sufficiently supplied with blood, are also damaged, which leads to loss of function (diabetic neuropathy, especially peripheral neuropathy).

Massive microangiopathy may cause microangiopathic hemolytic anemia (MAHA).