Cerebrovascular disease

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. 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]

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

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 Notch 3 gene located on chromosome 19.[19] The Notch 3 gene 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 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.[21] Causes of acquired cerebrovascular disease include atherosclerosis, embolism, aneurysms, and arterial dissections.[9] 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:[22]

Illustration of a cerebral aneurysm, demonstrating the bulge in an artery in the brain

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.

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.[26][27][28] 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.[29]

Arterial dissections are tears of the internal lining of arteries, often associated with trauma.[30] 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.[31]

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]

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.[39] The carotid arteries cover the majority of the cerebrum. The common carotid artery divides into the internal and the external carotid arteries. The internal carotid artery becomes the anterior cerebral artery and the middle central artery. The ACA transmits blood to the frontal parietal. From the basilar artery are two posterior cerebral arteries. Branches of the basilar and PCA supply the occipital lobe, brain stem, and the cerebellum.[40] Ischemia is the loss of blood flow to the focal region of the brain. This produces heterogeneous areas of ischemia at the affected vascular region, furthermore, blood flow is limited to a residual flow. Regions with blood flow of less than 10 mL/100 g of tissue/min are core regions (cells here die within minutes of a stroke). The ischemic penumbra with a blood flow of <25 ml/100g tissue/min, remain usable for more time (hours).[41]

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 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]

• Subarachnoid haemorrhage occurs when blood leaks out of damaged vessels into the cerebrospinal fluid in the 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]

Brain infarct