Cerebrovascular disease

Cerebrovascular disease includes a variety of

A stroke usually presents with an abrupt onset of a neurologic deficit – such as hemiplegia (one-sided weakness), numbness, aphasia (language impairment), or ataxia (loss of coordination) – attributable to a focal vascular lesion.^[7] The neurologic symptoms manifest within seconds because neurons need a continual supply of nutrients, including glucose and oxygen, that are provided by the blood. Therefore, if blood supply to the brain is impeded, injury and energy failure is rapid.^[8]

Besides hypertension, there are also many less common causes of cerebrovascular disease, including those that are

The most common presentation of cerebrovascular diseases is an acute stroke, which occurs when blood supply to the brain is compromised.

Other symptoms of cerebrovascular disease include migraines, seizures, epilepsy, or cognitive decline. However, cerebrovascular disease may go undetected for years until an acute stroke occurs. In addition, patients with some rare congenital cerebrovascular diseases may begin to have these symptoms in childhood.[15]

Causes

Congenital

Congenital diseases are medical conditions that are present at birth that may be associated with or inherited through genes.^[16] Examples of congenital cerebrovascular diseases include arteriovenous malformations, germinal matrix hemorrhage, and CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy).^[9] Arteriovenous malformations are abnormal tangles of blood vessels. Usually, a capillary bed separates arteries from veins, which protects the veins from the higher blood pressures that occur in arteries. In arteriovenous malformations, arteries are directly connected to veins, which increases the risk of venous rupture and hemorrhage. Cerebral arteriovenous malformations in the brain have a 2–4% chance of rupture each year. However, many arteriovenous malformations go unnoticed and are asymptomatic throughout a person's lifetime.^[17]

A germinal matrix hemorrhage is bleeding into the brain of premature infants caused by the rupture of fragile blood vessels within the germinal matrix of premature babies.^[18] The germinal matrix is a highly vascularized area within an unborn infant's brain from which brain cells, including neurons and glial cells, originate. Infants are at most risk to germinal matrix hemorrhages when they are born prematurely, before 32 weeks.^[18] The stresses exposed after birth, along with the fragile blood vessels, increase risk of hemorrhage. Signs and symptoms include flaccid weakness, seizures, abnormal posturing, or irregular respiration.^[18]

CADASIL is an inherited disorder caused by mutations in the NOTCH3 gene located on chromosome 19.^[19] NOTCH3 codes for a transmembrane protein whose function is not well-known. However, the mutation causes accumulation of this protein within small to medium-sized blood vessels.^[19] This disease often presents in early adulthood with migraines, stroke, mood disturbances, and cognitive deterioration. MRI shows white matter changes in the brain and also signs of repeated strokes. The diagnosis can be confirmed by gene testing.^[20]

Acquired

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.

Controlling these risk factors can reduce the incidence of atherosclerosis and stroke.^[25] 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.^{[citation needed]}

An

Idiopathic diseases are those that occur spontaneously without a known cause.^[32] Moyamoya is an example of an idiopathic cerebrovascular disorder that results in narrowing and occlusion of intracranial blood vessels.^[9] The most common presentation is stroke or transient ischemic attack, but cognitive decline within children may also be a presenting symptom.^[9][13] The disease may begin to show symptoms beginning in adolescence, but some may not have symptoms until adulthood.^[13]

Pathophysiology

Mechanism of brain cell death

When a reduction in blood flow lasting seconds occurs, the brain tissue suffers ischemia, or inadequate blood supply.^[33][34] If the interruption of blood flow is not restored in minutes, the tissue suffers infarction followed by tissue death.^[35] When the low cerebral blood flow persists for a longer duration, this may develop into an infarction in the border zones (areas of poor blood flow between the major cerebral artery distributions). In more severe instances, global hypoxia-ischemia causes widespread brain injury leading to a severe cognitive sequelae called hypoxic-ischemic encephalopathy.^[36]

An ischemic cascade occurs where an energetic molecular problem arises due to lack of oxygen and nutrients. The cascade results in decreased production of adenosine triphosphate (ATP), which is a high-energy molecule needed for cells in the brain to function.^[37] Consumption of ATP continues in spite of insufficient production, this causes total levels of ATP to decrease and lactate acidosis to become established (ionic homeostasis in neurons is lost). The downstream mechanisms of the ischemic cascade thus begins. Ion pumps no longer transport Ca²⁺ out of cell, this triggers release of glutamate, which in turn allows calcium into cell walls. In the end the apoptosis pathway is initiated and cell death occurs.^[38]

There are several arteries that supply oxygen to different areas of the brain, and damage or occlusion of any of them can result in stroke.

There are two main divisions of strokes: ischemic and hemorrhagic. Ischemic stroke involves decreased blood supply to regions of the brain, while hemorrhagic stroke is bleeding into or around the brain.[42]

Ischemic

• Ischemic stroke, the most common is caused by a blockage of a blood vessel in the brain, usually caused by thrombosis or emboli from a proximal arterial source or the heart, that leads to the brain being starved of oxygen.^[43] The neurologic signs and symptoms must last longer than 24 hours or the brain infarction is demonstrated, mainly by imaging techniques.^[44]
• Transient ischemic attack (TIA) also called a mini-stroke. This is a condition in which the blood flow to a region of the brain is blocked, but blood flow is quickly restored and the brain tissue can fully recover. The symptoms are only transient, leaving no sequelae, or long-term deficits.^[45] In order to diagnose this entity, all neurologic signs and symptoms must have been resolved within 24 hrs without evidence of brain infarction on brain imaging.^[46]

Hemorrhagic

• subarachnoid space around the brain.^[2] The most common cause of a subarachnoid hemorrhage is an aneurysm rupture due to the weakened blood vessel walls and increased wall stress.^[47] The neurologic symptoms are produced by the blood mass effect on neural structures, from the toxic effects of blood on the brain tissue, or by the increasing of intracranial pressure.^[48]
• Intracerebral haemorrhage is bleeding directly into the brain rather than around the brain.^[42] Causes and risk factors include hypertension, blood thinning medications, trauma, and arteriovenous malformations.^[49]

Diagnosis

• 
  MRI demonstrating white matter changes in the brain of patients with CADASIL
• 
  Brain infarct

Diagnoses of cerebrovascular disease may include:^[3]

• medical history
• physical exam
• neurological
  examination.
• acute stroke imaging is generally performed in significant symptoms of new onset.

It is important to differentiate the symptoms caused by a stroke from those caused by

Treatment for cerebrovascular disease may include medication, lifestyle changes, and surgery, depending on the cause.^[4]

Examples of medications are:

• antiplatelets (aspirin, clopidogrel)
• blood thinners (heparin, warfarin
  )
• antihypertensives:
  • ACE inhibitors
  • beta blockers
  • calcium channel blockers - in particular Nimodipine reduces the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage (SAH)^[51]
• anti-diabetic medications
  .

Surgical procedures include:

• endovascular surgery and vascular surgery
  (for future stroke prevention).

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.^[52]

Epidemiology

Worldwide, it is estimated there are 31 million stroke survivors, though about 6 million deaths were due to cerebrovascular disease (2nd most common cause of death in the world and 6th most common cause of disability).^[54]

Cerebrovascular disease primarily occurs with advanced age; the risk for developing it goes up significantly after 65 years of age. CVD tends to occur earlier than Alzheimer's Disease (which is rare before the age of 80).^{[citation needed]} In some countries such as Japan, CVD is more common than AD.^{[medical citation needed]}

In 2012, 6.4 million adults from the US had a stroke, which corresponds to 2.7% of the US. This is approximately 129,000 deaths in 2013.^[55]

Geographically, a "

Further reading

• Chan, Pak H. (2002-03-28). Cerebrovascular Disease: 22nd Princeton Conference. Cambridge University Press.
  ISBN 9781139439657
  .
• Mark, S. D; Wang, W; Fraumeni, J. F; Li, J.-Y; Taylor, P. R; Wang, G.-Q; Guo, W; Dawsey, S. M; Li, B; Blot, W. J (1996). "Lowered Risks of Hypertension and Cerebrovascular Disease after Vitamin/Mineral Supplementation: The Linxian Nutrition Intervention Trial". American Journal of Epidemiology. 143 (7): 658–664.
  PMID 8651227
  .
• Ning, Mingming; Lopez, Mary; Cao, Jing; Buonanno, Ferdinando S; Lo, Eng H (2012). "Application of proteomics to cerebrovascular disease". Electrophoresis. 33 (24): 3582–3597.
  PMID 23161401
  .

External links

Scholia has a topic profile for Cerebrovascular disease.

Wikimedia Commons has media related to Cerebrovascular diseases.