Ischemia and Infarction

Epidemiology:

• Etiologies:
• Hypotension (global cerebral ischemia)
• Atherosclerosis (focal cerebral ischemia)
• Embolism:
1. cardiac mural thrombi
1. MI
2. valvular disease
3. atrial fibrillation
2. atheroemboli from arteries:
1. carotid
3. paradoxical emboli:
4. cardiac surgery-associated
5. tumour
6. fat / bone marrow
1. after trauma
7. air
• Infectious vasculitis (usually in setting of immunosuppression):
1. toxoplasmosis
2. aspergillosis
3. CMV encephalitis
• Vasculitis :
1. Polyarteritis nodosa
2. primary angiitis of the central nervous system
3. other colagen vascular diseases
• hypercoagulable states
• dissecting aneurysm of extracranial arteries supplying the brain
• drug abuse
1. amphetamines
2. heroin
3. cocaine
• Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)
1. Notch3 mutations
• Cerebral amyloid angiopathy (CAA)
1. apoE genotype (epsilon-2 or epsilon-4 allele) increases risk of recurrence of hemorrhage in sporadic CAA
2. sporadic or familial

Common sites:

•  global cerebral ischemia (most susceptible regions):
• hippocampus (Pyramidal neurons of the Sommer sector (CA1)
• cerebellum (Purkinje cells)
• neocortex (Pyramidal neurons)
1. watershed zone a few cm lateral to interhemispheric fissure (between anterior and middle cerebral artery distributions)
• focal cerebral ischemia:
• areas with least collaterals (deep penetrating vessels):
1. thalamus
2. basal ganglia
3. deep white matter
• atherosclerosis:
1. carotid bifurcation
2. origin of middle cerebral a.
3. either end of the basilar a.
• embolism:
• MCA distribution
• Fat / bone marrow:
1. “shower embolization” – widespread hemorrhagic lesions involving white matter

Gross features:

• Global cerebral ischemia:
• Swollen brain
• Widened gyri
• Narrowed sulci
• Indistinct corticomedullary junction
• Focal cerebral ischemia:
• Non-hemorrhagic infarction:
• <6h:
1. little can be observed
• 48 hours:
1. pale
2. soft
3. swollen
4. indistinct corticomedullary junction
• 2-10 days:
1. gelatinous
2. friable
3. more distinct border on uninvolved tissue
• 10 days – 3 weeks:
1. liquefaction of infarcted area
2. fluid-filled cavity lined by dark gray tissue
3. eventual removal of dead tissue

Histologic features:

•  early (12-24h):
• acute neuronal injury
• cytotoxic and vasogenic edema
• decreased myelin staining (increased edema?)
• similar changes in astrocytes and oligodendroglia (later)
• 24-48h
• neutrophil infiltration starting at the edges of the lesion
• subacute (48h – 2 weeks):
• tissue necrosis
• macrophage infiltration
• vascular proliferation
• reactive gliosis
• repair (> 2weeks):
• macrophages still present (may persist for months to years)
• removal of necrotic tissue
• pseudolaminar necrosis (preservation of some layers and not others)
• loss of normal CNS structure
• gliosis
• > several months:
• receding of astrocytic nuclear and cytoplasmic enlargement
• wall of cavity shows dense feltwork of glial fibers and new capillaries and perivascular connective tissue fibres
• hemorrhagic infarction:
• addition of blood extravasation and resorption
• incomplete infarction:
• selective necrosis of neurons

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

Other features:

References:

•  Robbins & Cotran Pathologic Basis of Disease (2005)