Cerebral vasospasm is the prolonged, intense vasoconstriction of the larger conducting arteries in the subarachnoid space which is initially surrounded by a clot. Significant narrowing of the blood vessels in the brain develops gradually over the first few days after the aneurysmal rupture. This kind of narrowing usually is maximal in about a week's time following intracerebral haemorrhage. Vasospasm is one of the leading causes of death after the aneurysmal rupture along with the effect of the initial haemorrhage and later bleeding. [1]
Cerebral vasospasm is a common and severe complication following aneurysmal subarachnoid hemorrhage, occurring in 50-90% of cases after aneurysm rupture. Moderate or severe vasospasm in one or more cerebral arteries develops in approximately two-thirds of patients with ruptured aneurysms. Of these, nearly half exhibit symptoms of cerebral ischemia. [2] Infarction occurs in about half of the symptomatic patients and is significantly associated with factors such as advanced age, a history of hypertension, or diabetes mellitus. Despite improvements in the management of subarachnoid hemorrhage, the overall risk of death and disability remains approximately 10%.[ citation needed ]
The pathogenesis of cerebral vasospasm, particularly after subarachnoid hemorrhage, is complex and is thought to involve several mechanisms that lead to the narrowing of cerebral arteries, reducing blood flow to the brain. Currently understood mechanisms of vasospasm are as follows:
When an aneurysm ruptures, blood enters the subarachnoid space, forming clots. Hemoglobin, released from these clots, plays a key role in initiating vasospasm. [3] Hemoglobin scavenges nitric oxide, a critical vasodilator produced by the endothelium (the inner lining of blood vessels). The loss of nitric oxide leads to unopposed contraction of smooth muscle cells in the vessel wall, resulting in acute vasoconstriction. This process is calcium-dependent and represents the early, more reversible stage of vasospasm. [4]
Endothelial cells regulate vascular tone by producing vasodilators (like nitric oxide and prostacyclin) and vasoconstrictors (like endothelin). In vasospasm, endothelial damage disrupts this balance, reducing vasodilator production while increasing levels of vasoconstrictors. [5] Elevated levels of endothelin, a potent vasoconstrictor, are consistently observed in patients with vasospasm, contributing to prolonged and sustained narrowing of the arteries. [6]
While early vasospasm is largely mediated by functional changes in smooth muscle contraction, chronic vasospasm involves more permanent structural damage to the vessel wall. In chronic stages, smooth muscle contraction becomes less reversible because of remodeling and damage to the layers of the blood vessels. [7] This damage impairs normal vessel function and leads to sustained vasoconstriction. [2]
Blood in the subarachnoid space triggers an inflammatory response, which includes the release of cytokines, leukocyte infiltration, and activation of microglia. [8] This inflammation contributes to oxidative stress, further damaging the endothelial lining and smooth muscle cells. The inflammatory response exacerbates the release of vasoconstrictors like endothelin and decreases the availability of vasodilators like nitrous oxide, worsening vasospasm. [8]
The smooth muscle contraction in vasospasm is heavily dependent on calcium signaling. [4] During acute vasospasm, calcium influx into smooth muscle cells causes contraction. In chronic vasospasm, alterations in calcium-handling mechanisms in vascular smooth muscle cells may contribute to persistent vasoconstriction that does not respond to traditional vasodilatory signals. [2]
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The most critical risk factor for vasospasm after subarachnoid hemorrhage is the presence of a large volume of persistent subarachnoid clot. [2] Additional factors that increase the risk include:
It is critical to rule out other potential causes of delayed neurological deterioration such as hyponatremia, hypoxemia, infection, cerebral edema, or rebleeding of aneurysms. [9]
Cerebral vasospasm is primarily diagnosed using transcranial Doppler, which measures the velocity of blood flowing through cerebral arteries. Increased velocities indicate narrowing of the blood vessels. Vasospasm is considered significant at velocities exceeding 120 cm/second and severe at velocities above 200 cm/second. [2] Other diagnostic methods include:
Several approaches have been developed to predict and prevent vasospasm following subarachnoid hemorrhage. The modified Fischer scale, which uses parameters such as clot volume and distribution on CT scans, helps predict the risk and prognosis of vasospasm. [2] There is also evidence that aneurysm repair through coiling, compared to microsurgical repair, may reduce the risk of vasospasm. [9]
Nimodipine, an oral calcium channel blocker, is the standard drug for the prevention of vasospasm following subarachnoid hemorrhage. [9] While it does not reverse vasospasm once it has occurred, it is effective in reducing the overall incidence. Early mobilization and rehabilitation have also been shown to significantly decrease the frequency and severity of vasospasm in some prospective interventional studies.[ citation needed ]
The management of vasospasm includes supportive management such as staying within adequate blood pressure and heart rate ranges, managing seizures, and providing supportive care. Despite various investigational preventive treatments, most have not shown consistent efficacy. An example is IV magnesium sulfate, which was initially considered for its neuroprotective properties, but was not found to be effective in reducing the risk of vasospasm or infarction in the large multicenter IMASH and IMASH-2 trials [10] [11]
Current clinical treatments include:
While fluid therapy is beneficial for patients with poor neurological status, prophylactic hypervolemia or hypertension is not recommended due to the risk of complications, as outlined by the American Heart Association guidelines. [12]
A cerebral arteriovenous malformation is an abnormal connection between the arteries and veins in the brain—specifically, an arteriovenous malformation in the cerebrum.
Blood vessels are the tubular structures of a circulatory system that transport blood throughout a vertebrate's body. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste and carbon dioxide away from the tissues. Some tissues such as cartilage, epithelium, and the lens and cornea of the eye are not supplied with blood vessels and are termed avascular.
An intracranial aneurysm, also known as a cerebral aneurysm, is a cerebrovascular disorder characterized by a localized dilation or ballooning of a blood vessel in the brain due to a weakness in the vessel wall. These aneurysms can occur in any part of the brain but are most commonly found in the arteries of the cerebral arterial circle. The risk of rupture varies with the size and location of the aneurysm, with those in the posterior circulation being more prone to rupture.
An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus for clot formation (thrombosis) and embolization. As an aneurysm increases in size, the risk of rupture, which leads to uncontrolled bleeding, increases. Although they may occur in any blood vessel, particularly lethal examples include aneurysms of the circle of Willis in the brain, aortic aneurysms affecting the thoracic aorta, and abdominal aortic aneurysms. Aneurysms can arise in the heart itself following a heart attack, including both ventricular and atrial septal aneurysms. There are congenital atrial septal aneurysms, a rare heart defect.
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in controlling hemorrhage and reducing acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus retaining body heat or increasing vascular resistance. This makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure.
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.
Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, weakness, numbness, and sometimes seizures. Neck stiffness or neck pain are also relatively common. In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed.
Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds, subarachnoid bleeds, epidural bleeds, and subdural bleeds.
Papaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms, occasionally in the treatment of erectile dysfunction and acute mesenteric ischemia. While it is found in the opium poppy, papaverine differs in both structure and pharmacological action from the analgesic morphine and its derivatives.
Cerebral salt-wasting syndrome (CSWS), also written cerebral salt wasting syndrome, is a rare endocrine condition featuring a low blood sodium concentration and dehydration in response to injury (trauma) or the presence of tumors in or surrounding the brain. In this condition, the kidney is functioning normally but excreting excessive sodium. The condition was initially described in 1950. Its cause and management remain controversial. In the current literature across several fields, including neurology, neurosurgery, nephrology, and critical care medicine, there is controversy over whether CSWS is a distinct condition, or a special form of syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis).
A thunderclap headache is a headache that is severe and has a sudden onset. It is defined as a severe headache that takes seconds to minutes to reach maximum intensity. Although approximately 75% are attributed to "primary" headaches—headache disorder, non-specific headache, idiopathic thunderclap headache, or uncertain headache disorder—the remainder are secondary to other causes, which can include some extremely dangerous acute conditions, as well as infections and other conditions. Usually, further investigations are performed to identify the underlying cause.
Vasomotor refers to actions upon a blood vessel which alter its diameter. More specifically, it can refer to vasodilator action and vasoconstrictor action.
The anterior clinoid process is a posterior projection of the sphenoid bone at the junction of the medial end of either lesser wing of sphenoid bone with the body of sphenoid bone. The bilateral processes flank the sella turcica anteriorly.
Coronary vasospasm refers to when a coronary artery suddenly undergoes either complete or sub-total temporary occlusion.
Fasudil (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke patients. It has been found to be effective for the treatment of pulmonary hypertension. It has been demonstrated that fasudil could improve memory in normal mice, identifying the drug as a possible treatment for age-related or neurodegenerative memory loss.
Joshua B. Bederson is an American neurosurgeon, Leonard I. Malis, MD/Corinne and Joseph Graber Professor of Neurosurgery, and System Chair of Neurosurgery at the Mount Sinai Health System in New York City. He is a Fellow of the American College of Surgeons, and an attending neurosurgeon at The Mount Sinai Hospital.
Vein of Galen aneurysmal malformations(VGAMs) and Vein of Galen aneurysmal dilations (VGADs) are the most frequent arteriovenous malformations in infants and fetuses. A VGAM consists of a tangled mass of dilated vessels supplied by an enlarged artery. The malformation increases greatly in size with age, although the mechanism of the increase is unknown. Dilation of the great cerebral vein of Galen is a secondary result of the force of arterial blood either directly from an artery via an arteriovenous fistula or by way of a tributary vein that receives the blood directly from an artery. There is usually a venous anomaly downstream from the draining vein that, together with the high blood flow into the great cerebral vein of Galen causes its dilation. The right sided cardiac chambers and pulmonary arteries also develop mild to severe dilation.
Endovascular coiling is an endovascular treatment for intracranial aneurysms and bleeding throughout the body. The procedure reduces blood circulation to the aneurysm through the use of microsurgical detachable platinum wires, with the clinician inserting one or more into the aneurysm until it is determined that blood flow is no longer occurring within the space. It is one of two main treatments for cerebral aneurysms, the other being surgical clipping. Clipping is an alternative to stenting for bleeding.
Alexander Coon is an American neurosurgeon who is the director of endovascular and cerebrovascular neurosurgery at the Carondelet Neurological Institute of St. Joseph's and St. Mary's Hospitals in Tucson, Arizona. He was previously the director of endovascular neurosurgery at the Johns Hopkins Hospital and an assistant professor of neurosurgery, neurology, and radiology at the Johns Hopkins Hospital. He is known for his work in cerebrovascular and endovascular neurosurgery and his research in neuroendovascular devices and clinical outcomes in the treatment of cerebral aneurysms, subarachnoid hemorrhage, and AVMs.