Cerebrovascular Accidents and Hemorrhages

Cerebrovascular Diseases

• Cerebrovascular diseases are brain disorders caused by pathologic processes involving blood vessels.
• Three main pathogenic mechanisms:
  • Thrombotic occlusion
  • Embolic occlusion
  • Vascular rupture

Hemorrhage

• Hemorrhage into the subarachnoid space can result from:
  • Vascular malformation
  • Trauma
  • Rupture of an intracerebral hemorrhage into the ventricular system
  • Coagulopathies
  • Tumors
• Subarachnoid hemorrhages can obstruct CSF flow or disrupt CSF resorption, leading to hydrocephalus.

Vascular Malformations

• Vascular malformations of the brain are classified into four principal types:
  • Arteriovenous malformations (AVMs)
  • Cavernous malformations
  • Capillary telangiectasias
  • Venous angiomas
• AVMs are the most common and affect males more than females (2:1).
• AVMs most commonly manifest between 10 and 30 years of age with seizures, intracerebral hemorrhage, or subarachnoid hemorrhage.

Stroke

• Stroke is the clinical designation applied to all cerebrovascular diseases when symptoms begin acutely.
• Hypoxia, ischemia, and infarction can occur due to:
  • Functional hypoxia (e.g., high altitude, severe anemia)
  • Ischemia (e.g., transient or permanent, due to tissue hypoperfusion)

Global Cerebral Ischemia

• Widespread ischemic-hypoxic injury can occur in the setting of severe systemic hypotension, usually when systolic pressures fall below 50 mm Hg.
• Clinical outcome varies with the severity and duration of the insult.
• Mild global cerebral ischemia may result in transient postischemic confusional state, with eventual complete recovery.
• Severe global cerebral ischemia can result in widespread neuronal death, with patients often remaining severely impaired neurologically and in a persistent vegetative state.

Morphology

• In the setting of global ischemia, the brain is swollen, with wide gyri and narrowed sulci.
• Early changes include acute neuronal cell change (red neurons).
• Subacute changes include necrosis of tissue, influx of macrophages, vascular proliferation, and reactive gliosis.
• Repair is characterized by removal of necrotic tissue and gliosis.

Focal Cerebral Ischemia

• Cerebral arterial occlusion leads to focal ischemia and then to infarction in the distribution of the compromised vessel.
• Infarct size and location can be modified by collateral blood flow.
• Embolic infarctions are more common than infarctions due to thrombosis.
• Cardiac mural thrombi are a frequent source of emboli.
• Thrombotic occlusions usually occur at the carotid bifurcation, the origin of the middle cerebral artery, and either end of the basilar artery.

Infarcts

• Infarcts can be divided into two broad groups:
  • Nonhemorrhagic infarcts result from acute vascular occlusions and may evolve into hemorrhagic infarcts.
  • Hemorrhagic infarcts usually manifest as multiple, sometimes confluent, petechial hemorrhages.
• Macroscopic appearance of a nonhemorrhagic infarct evolves over time:
  • Unchanged in appearance in the first 6 hours
  • Pale, soft, and swollen by 48 hours
  • Gelatinous and friable from days 2 to 10
  • Fluid-filled cavity from day 10 to week 3

Microscopically

• Tissue reaction follows a characteristic sequence:
  • Ischemic neuronal change (red neurons) and cytotoxic and vasogenic edema appear after the first 12 hours.

Intracranial Hemorrhage

• Hemorrhages within the brain are caused by:
  • Hypertension and other diseases leading to vascular wall injury
  • Structural lesions such as arteriovenous and cavernous malformations
  • Tumors
• Subarachnoid hemorrhages most commonly result from ruptured aneurysms.

Primary Brain Parenchymal Hemorrhage

• Spontaneous (nontraumatic) intraparenchymal hemorrhages are most common in mid to late adult life, with a peak incidence at about 60 years of age.
• Most are due to the rupture of a small intraparenchymal vessel.
• Hypertension is the leading underlying cause, and brain hemorrhage accounts for roughly 15% of deaths among individuals with chronic hypertension.
• Hypertensive intraparenchymal hemorrhages typically occur in the basal ganglia, thalamus, pons, and cerebellum, with the location and size of the bleed determining its clinical manifestations.

Cerebrovascular Diseases

• Cerebrovascular diseases are brain disorders caused by pathologic processes involving blood vessels.
• The three main pathogenic mechanisms are:
  • Thrombotic occlusion
  • Embolic occlusion
  • Vascular rupture

Hypoxia, Ischemia, and Infarction

• Cerebral blood flow normally remains stable over a wide range of blood pressure and intracranial pressure due to autoregulation of vascular resistance.
• The brain may be deprived of oxygen by two general mechanisms:
  • Functional hypoxia (e.g., high altitude, severe anemia)
  • Ischemia (transient or permanent, due to tissue hypoperfusion)

Global Cerebral Ischemia

• Widespread ischemic-hypoxic injury can occur in the setting of severe systemic hypotension, usually when systolic pressures fall below 50 mm Hg.
• The clinical outcome varies with the severity and duration of the insult.
• In severe global cerebral ischemia, widespread neuronal death occurs, and patients who survive often remain severely impaired neurologically and in a persistent vegetative state.

Morphology

• In the setting of global ischemia, the brain is swollen, with wide gyri and narrowed sulci.
• Early changes (12-24 hours after the insult) include acute neuronal cell change (red neurons).
• Subacute changes (24 hours to 2 weeks) include necrosis of tissue, influx of macrophages, vascular proliferation, and reactive gliosis.

Microscopically

• The tissue reaction follows a characteristic sequence.
• After the first 12 hours, ischemic neuronal change (red neurons) and cytotoxic and vasogenic edema appear.

Intracranial Hemorrhage

• Hemorrhages within the brain are caused by:
  • Hypertension and other diseases leading to vascular wall injury
  • Structural lesions (e.g., arteriovenous and cavernous malformations)
  • Tumors

Primary Brain Parenchymal Hemorrhage

• Spontaneous (nontraumatic) intraparenchymal hemorrhages are most common in mid to late adult life, with a peak incidence at about 60 years of age.
• Most are due to the rupture of a small intraparenchymal vessel.
• Hypertension is the leading underlying cause, and brain hemorrhage accounts for roughly 15% of deaths among individuals with chronic hypertension.

Subarachnoid Hemorrhage and Saccular Aneurysms

• The most frequent cause of clinically significant nontraumatic subarachnoid hemorrhage is rupture of a saccular (berry) aneurysm.

Focal Cerebral Ischemia

• Cerebral arterial occlusion leads to focal ischemia and then to infarction in the distribution of the compromised vessel.
• The size, location, and shape of the infarct and the extent of tissue damage may be modified by collateral blood flow.

Embolic Infarctions

• More common than infarctions due to thrombosis, cardiac mural thrombi are a frequent source of emboli.
• Myocardial dysfunction, valvular disease, and atrial fibrillation are important predisposing factors.

Thrombotic Occlusions

• Thrombotic occlusions usually are superimposed on atherosclerotic plaques.
• Common sites are the carotid bifurcation, the origin of the middle cerebral artery, and either end of the basilar artery.

Infarcts

• Infarcts can be divided into two broad groups:
  • Nonhemorrhagic infarcts result from acute vascular occlusions and may evolve into hemorrhagic infarcts when there is reperfusion of ischemic tissue.
  • Hemorrhagic infarcts manifest as multiple, sometimes confluent, petechial hemorrhages.

Vascular Malformations

• Vascular malformations of the brain are classified into four principal types:
  • Arteriovenous malformations (AVMs)
  • Cavernous malformations
  • Capillary telangiectasias
  • Venous angiomas