CHAPTER TWO
CEREBRAL ISCHEMIA AND STROKE

HEMORRHAGIC STROKES(INTRACEREBRAL AND SUBARACHNOID HEMORRHAGE)

Approximately 15% to 20% of strokes are due to rupture of blood vessels with intracerebral or subarachnoid hemorrhage. The three major causes of hemorrhagic stroke are hypertension, ruptured arterial aneurysms, and arteriovenous malformations. Intracerebral and subarachnoid hemorrhage are also very common in head trauma.

HYPERTENSIVE INTRACEREBRAL HEMORRHAGE

Hypertensive basal ganglionic hemorrhage	Hypertensive pontine hemorrhage

This hemorrhage results from rupture of small, penetrating arteries. Hypertensive angiopathy (small vessel disease) stiffens vessel walls and makes them fragile. This, in conjunction with increased pressure from within the lumen, causes vascular rupture and hemorrhage. The most frequent sites of hypertensive intracerebral hemorrhage are the basal ganglia and thalamus. Less commonly, hypertensive intracerebral hemorrhage involves the cerebellum, the pons, and occasionally the subcortical white matter. Large intracerebral hemorrhages cause increased intracranial pressure and carry a high fatality rate. Improved control of hypertension in the last 20 years has led to a dramatic reduction in the incidence of hypertensive intracerebral hemorrhage.

ARTERIAL ANEURYSMS

Berry aneurysm	Large aneurysm at the cerebello-pontine angle
Subarachnoid hemorrhage	Intraventricular hemorrhage

Intracranial aneurysms (IA), also referred to as saccular or berry aneurysms, develop in the walls of major cerebral arteries at branching points, where there are gaps in the media and internal elastica. The majority of them are on the circle of Willis and the first bifurcation of the middle cerebral artery. They are multiple in 20% of the cases. Nonruptured aneurysms are seen in 2% of adult autopsies. The defects in the vessel wall are present since birth but aneurysms are rare in children; they develop later in adulthood, due to gradual weakening of vessels from the constant force of even normal blood pressure and structural changes that occur with advancing age. They are more common in women than men and occur with increased frequency in patients with coarctation of the aorta and polycystic kidney disease. Other risk factors include smoking and alcohol consumption.

Clinical observations have established a familial incidence of IAs. A small proportion are inherited as an autosomal dominant trait and are linked to several genes and chromosomal loci, including some that encode collagen and other structural proteins that are found in vessel walls. There is an increased risk in first degree relatives of patients with aneurysms.

Large IAs can cause symptoms by compressing cranial nerves, vessels, and brain tissue but their most feared complication is rupture. The vessels bearing the aneurysms are in the subarachnoid space. Consequently, their rupture causes subarachnoid hemorrhage (SAH). Blood spurts out of the ruptured aneurysm with a force that can tear the soft brain. If the stream of blood is directed toward the brain, it may cause intracerebral and intraventricular hemorrhage. The larger the aneurysm, the higher is the likelihood of rupture.

Typically, SAH from a ruptured IA causes a sudden severe headache with relative preservation of consciousness and without focal neurological deficits. Approximately one week later, vascular spasm develops, causing additional ischemia. Vasospasm affects arteries that are surrounded by subarachnoid blood clots and is triggered by products released form hemolyzed RBCs. A massive aneurysmal bleed raises intracranial pressure, resulting in arrest of cerebral perfusion, unconsciousness, and HIE. Hydrocephalus may develop due to blockage of CSF flow by subarachnoid clots and from meningeal fibrosis, which results from their organization. About half of patients with aneurysmal bleeds die in six months, some from the first and most from recurrent bleeds. Survivors have serious long-term disabilities and a significant risk of rebleeding.

Fusiform aneurysms are vascular dilatations due to atherosclerosis. They are seen most commonly in the basilar artery and are associated with thrombosis and brainstem infarction and less frequently with rupture and subarachnoid hemorrhage.

ARTERIOVENOUS MALFORMATIONS (AVMs)

Arteriovenous malformation	Arteriovenous malformation

AVMs are developmental abnormalities of cerebral vessels. They consist of a tangle of abnormal vessels interposed between a feeding artery and a draining vein. Most AVMs are in the distribution of the middle cerebral artery but they may occur anywhere. In addition to classical AVMs, there are several other related types of vascular anomalies and hamartomas that have similar manifestations. The abnormal vessels may be in brain tissue, in the subarachnoid space, or both. AVMs and other vascular anomalies cause seizures and neurologic deficits due to chronic compression and ischemia of brain tissue. Their most feared outcome is intracerebral and subarachnoid hemorrhage. There may be multiple episodes of bleeding over many years (sometimes since childhood) manifested by headaches, a single catastrophic bleed, or both. Patients with AVMs also have an increased incidence of aneurysms. A related vascular lesion, cerebral cavernous malformation (CCM), consists of clusters of cavernous vessels without intervening stroma. CCMs are dominantly inherited and may be multiple. They cause recurrent hemorrhage and seizures.

OTHER CAUSES OF HEMORRHAGIC STROKE

Cerebral amyloid angiopathy	Lobar hemorrhage

One of the most frequent causes of intracerebral hemorrhage is anticoagulants therapy. The incidence of anticoagulant-associated intracerebral hemorrhage has increased markedly in recent years, following the increasing use of warfarin. Less frequently, intracerebral and subarachnoid hemorrhage is caused by cerebral angiitis (polyarteritis nodosa, granulomatous arteritis, SLE, bacterial arteritis) and cerebral amyloid angiopathy (CAA). Most CAA cases are sporadic but there are several familial, autosomal dominant, forms also. The amyloid peptide in sporadic CAA is beta amyloid, and most of these patients also have Alzheimer's disease (AD). Some of the familial CAAs are caused by mutations of the beta amyloid precursor protein gene on chromosome 21 and these patients also have beta amyloid deposition and autosomal dominant AD. Other familial CAAs are caused by mutations of other genes. These patients do not have AD and the vascular amyloid has a different chemical composition. Amyloid deposition causes leptomeningeal and cortical vessels to become fragile, resulting in hemorrhages, especially in the subcortical white matter (lobar hemorrhages). CAA also causes ischemic infarcts and leukoencephalopathy (see also small vessel disease).

Other angiopathies (Ehlers-Danlos syndrome, homocystinuria, amphetamine vasculitis) and genetic or acquired coagulopathies and platelet disorders may also cause hemorrhagic strokes.

Further reading:

Nahed BV, Bydon M, Ozturk AK, et al. Genetics of intracranial aneurysms. Neurosurgery. 2007;60:213-25. PubMed

Flaherty ML, Kissela B, Woo D, et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007;68:116-21. PubMed

Updated: December, 2008