III. ISCHEMIC DISORDERS

A. General Characteristics

Ischemia, the failure of cerebral blood flow to a region, results in infarction (complete necrosis). Experimental studies suggest that the rapidly lethal effects on neurons are due not only to the sensitivity of those cells to hypoxia but also to the inability of the cerebrovascular bed to recover from a period of severe ischemia, i.e. glial cells swell and compress capillaries.

The most common cerebrovascular lesions are ischemic in nature - 85% of "strokes" are due to thrombosis or occlusive vascular disease. The vasculature that leads from the heart to the brain is the most common location of occlusive disease.

The site of infarction and resulting clinical signs depend on many factors in addition to the site of occlusion, including the extent of collateral circulation, the presence of anomalies and the suddenness of occlusion. For example, when occlusion of the internal carotid artery occurs, the infarction is most commonly in the distribution of the middle cerebral artery because the area supplied by the anterior cerebral artery receives blood via the anterior communicating artery.

Occasionally cerebrovascular lesions result from generalized reduction of cerebral perfusion. For example, if a failing myocardium inadequately perfuses a vascular system already interrupted by moderate amounts of occlusive disease, infarctions of the brain may result. These may be either "watershed" infarcts or localized to distributions of specific arterial branches. In addition, generalized reduction of blood flow is associated with hypoxic encephalopathy, with widespread damage. Hypoxic encephalopathy is discussed further in the Toxic-Metabolic-Nutritional Disorders unit.

B. Thrombosis (Arterial)--Pale Infarction

1. Pathogenesis

a. Vascular occlusion due to atheroma - most common cause of stroke. The most common sites are the origins of the internal carotid arteries, vertebral arteries and middle cerebral arteries.

b. Variations in coagulability of blood; e.g. post-operative changes, polycythemia

c. Reduction of circulation in an impaired system; e.g. sleep, hypotension, immobilization for fracture.

d.Vascular occlusion secondary to vasculitis

2. Incidence

Since the majority of cases of thrombosis are related to atherosclerosis, cerebral thrombosis generally occurs in individuals who have one or more risk factors producing accelerated atherosclerosis. These factors include hypertension, diabetes mellitus, obesity, hyperuricemia, hypothyroidism, abnormal serum lipid levels, and smoking. In young women, the combination of smoking and birth control pills is a significant risk factor.

3. Clinical Features

Infarction of the brain in an area supplied by a cerebral artery tends to produce a clearly recognizable clinical syndrome. Occlusion is preceded by transient ischemic attacks in about 50% of cases. The onset of symptoms is sudden, and gradual improvement may occur beginning after a few days. Specific symptoms depend on the site of infarction. A brief summary of the syndromes produced by infarction in the territory of major arteries is provided below:

Middle cerebral artery: paralysis of the contralateral face, arm and leg; sensory impairment over the contralateral face, arm and leg; homonymous hemianopsia or homonymous quadrantonopsia; paralysis of conjugate gaze to the opposite side; aphasia if the lesion is on the dominant side (usually the left side of brain); unilateral neglect and agnosia for half of external space if the lesion is on the non-dominant side (usually right side).

Anterior cerebral artery: paralysis of contralateral foot and leg; sensory loss over toes, foot and leg; impairment of gait and stance.

Posterior cerebral artery: homonymous hemianopsia; hallucinations; sensory loss and spontaneous pain (if central territory including thalamus is involved - called thalamic syndrome); third nerve palsy and contralateral hemiplegia (if central territory including midbrain is involved - called Weber's syndrome).

Posterior inferior cerebellar artery: pain, numbness, impaired sensation in face ipsilateral to lesion; impaired pain and temperature sensation in bocy contralateral to lesion; ataxia of limbs; falling to side of lesion; nystagmus, vertigo, Horner's syndrome, dysphagia, hoarseness.

4. Gross Pathology

a. In the first 48 hours a lesion is difficult to discern at autopsy. After fixation, the infarcted area appears soft and swollen.

b. Edema reaches a maximum in 4-5 days. Edema acts as a space-occupying lesion and may cause adjacent damage.

c. Cell loss, myelin breakdown, phagocytosis and glial scar production result in shrinkage and distortion of structure; cysts may form in large infarcts and compensatory ventricular enlargement may occur.

This image shows a recent infarct in the temporal lobe on the right, with edema indicated by blurring of margin between gray and white matter, gyri pushed out, cracking between temporal lobe white matter and the adjacent gray matter.

This coronal section shows an old lacunar infarct in putamen and internal capsule on right side of image.

This coronal section shows an old infarct in distribution of middle cerebral artery; cyst formation and compensatory verticular enlargement are prominent.

Sections of caudal pons, rostral pons and midbrain from the brain shown at left illustrate Wallerian degeneration of corticospinal tract on right side of each image secondary to the infarct in the distribution of the middle cerebral artery.

5. Microscopic Pathology

a. After about 12 hours: neuronal nuclear pyknosis and cytoplasmic eosinophilia (red neurons)

b. After 2 days: polymorphonuclear leukocyte infiltrate; capillary prominence; endothelial swelling; vacuolation of white matter

c. After 3-5 days: macrophages appear

d. After 7-21 days: astrocytes proliferate and may become gemistocytic; glial fibers increase; cysts are traversed by blood vessels and surrounded by firm glial tissue

A microscopic field (high-power) from an old infarct shows lipid-laden macrophages (brownish cytoplasm) and glial fibrils (pink) in a cystic region.

C. Embolism

1. Pathogenesis

Emboli are circulating bodies which lodge in vessels, generally involving the smaller vessels. The commonest cause of cerebral embolism is a thrombotic embolus in the middle cerebral artery. After an embolus occludes a vessel, the tissue undergoes infarction and the distal portion of the vessel becomes necrotic. If the occlusive material breaks up or moves into the necrotic area of the vessel, blood disgorges through the weakened wall and floods into the area that has been infarcted. The result is a hemorrhagic infarction. Hemorrhagic infarction often occurs with emboli, but pale infarctions may also result.

2. Incidence

Thromboemboli occur most often in patients with valvular heart disease, cardiac disease with atrial fibrillations, or myocardial infarction. Fat emboli may occur following lung injury or surgery. Nitrogen bubbles may form with rapid decompression in deep sea divers.

3. Clinical Course

Clinical symptoms consist of sudden onset of focal impairment, within seconds to minutes. Most patients survive and marked clinical improvement often occurs.

4. Pathological Changes

Emboli most often produce tiny hemorrhagic infarcts in the cerebral cortex although one larger region may be involved. The area involved is generally smaller than for thrombotic occlusion.

A recent hemorrhagic infarct is present on the left side of the image and an old pale infarct on the right side. This section shows a large hemorrhagic infarct produced by embolism.

5. Types of Emboli -- the most common is thromboemboli

a.Thromboemboli--most frequently from the heart; may also arise from atheromatous plaques on carotid and vertebral-basilar arteries

b. Fat Emboli--fat globules associated with trauma to long bones

c. Air Emboli--associated with trauma to heart, lungs, orvessels, e.g in surgical procedures

d. Metastatic Deposits--from systemic tumors

e. Septic Emboli--most often seen in bacterial endocarditis; may cause brain abscess or other secondary conditions.

f. Nitrogen Bubbles--form with rapid decompression (Caisson disease)

D. Venous or Dural Sinus Thrombosis--Hemorrhagic Infarction

This is the least common pattern of cerebral infarction. Hemorrhagic infarction occurs when blood stasis in large veins or venous sinuses leads to infarction, then, increased pressure disrupts capillaries causing blood to enter the infarcted areas. Abrupt occlusion of several cerebral veins or dural sinuses is necessary to produce a large hemorrhagic infarct. Slowly progressive venous or dural sinus occlusion rarely results in tissue necrosis. Predisposing factors include dehydration in children, spread of infection from adjacent foci (nasal sinus or middle ear) and disorders that cause hypercoagulability of blood.

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