Pathology Ch28 -- The Central Nervous System -- PARTIAL pp1263-1271 (Cerebrovascular Disease)
Cerebrovascular Disease
 Injury to the brain as a consequence of altered blood flow (ischemic or hemorrhagic etiologies)
 Hypoxia, Ischemia, and Infarction
o Brain requires constant supply of glucose and O2
 Ischemia > depletion of ATP > loss of membrane potential > loss of neuronal activity
 "Penumbra" = area of at-risk tissue between necrotic tissue and normal brain
o Global Cerebral Ischemia
 Diffuse ischemic/hypoxic encephalopathy when there is a generalized reduction of cerebral perfusion
 Seen in cardiac arrest, shock, and severe hypotension
 Neurons are most sensitive
 Pyramidal cell layer of hippocampus - "Sommer sector"**
 Cerebellar Purkinje cells
 Pyramidal neurons in cerebral cortex
 Mild cases can be recovered from after initial bout of confusion
 Severe cases result in persistent vegetative state > must be maintained on ventilator
 Brain undergoes autolysis > gradual liquefaction ("respirator brain")
 Border zone ("watershed") infarcts occur at areas furthest away from arterial blood supply
 Damage here produces sickle-shaped band of necrosis
 Usually seen after hypotensive episodes
 Morphology:
 Brain becomes edemantous and swollen > widening of gyri and narrowing of sulci
 Early changes (12-24hr after insult) = damage seen in neurons before glial cells
 Subacute changes (24hr-2 weeks) = tissue necrosis, influx of macrophages, vascular proliferation
 Repair (after 2 weeks) = removal of necrotic tissue, loss of normal CNS architecture, gliosis
o Focal Cerebral Ischemia
 Follows reduction or cessation of blood flow to localized area of brain
 Extent of damage depends on duration of ischemia and adequacy of collateral flow
 Embolism:
 Cardiac mural thrombi are most common
 Thromboemboli from arteries, often from artheromatous plaques in carotid arteries
 "Shower embolization" - fat, may occur after fractures
 Thombotic occlusions:
 Most commonly associated w/ atherosclerosis and plaque rupture
 Most common @ carotid bifurcation, origin of middle cerebral artery, basilar artery ends
 Cause progressive narrowing of lumen
 May progress to embolization
 Inflammatory processes:
 Infectious vasculitis seen in immunosuppression and opportunistic infection
 Polyarteritis nodosa = non-infectious vasculitides
 Primary angiitis of the CNS = inflammatory disorder
o Nonhemorrhagic Infarct (initial infarction)
o Hemorrhagic Infarct (secondary to reperfusion)
 Hypertensive Cerebrovascular Disease
o Lacunar Infarcts
 HTN affects deep penetrating vasculature that supply basal ganglia, brainstem, and white matter
 Vasculature develops arteriolar sclerosis > may become occluded
 "Lacunes" = single or multiple, small, cavitary infarcts
 Occur in lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, pons
o Slit Hemorrhages
 HTN > rupture of small-caliber penetrating vessels > small hemorrhages
 Hemorrhages resorb > leave behind slit-like cavity ("slit hemorrhage")
o Hypertensive Encephalopathy
 Diffuse cerebral dysfunction (headaches, confusion, vomiting, convulsion) that can lead to coma
 Syndrome often does not remit spontaneously
 Vascular (multi-infarct) dementia caused by multifocal vascular disease of several types:

 (1) Cerebral athersosclerosis
 (2) Vessel thrombosis or embolization from carotid vessels or from heart
 (3) Cerebral arteriolar sclerosis from chronic hypertension
 Binswanger disease = when injury preferentially involves large areas of subcortical white matter
Intracranial Hemorrhage
o Intraparenchymal Hemorrhage (within the brain)
 Rupture of small intraparenchymal vessels > hemorrhage within brain
 Often associated w/ sudden onset of neurologic symptoms (stroke)
 Ganglionic hemorrhages = within basal ganglia and thalamus (due to HTN)
 Chronic HTN associated w/ Charcot-Bouchard microaneurysms = site of rupture
 Lobar hemorrhages = within cerebral hemispheres (due to cerebral amyiloid angiopathy)
 Amyloidogenic peptides deposited in walls of medium and small meningeal and cortical vessels
o Same peptides found in Alzheimer's disease
 Deposition weakens vessel wall > hemorrhage
 Location of hemorrhage determines the clinical manifestations
o Subarachnoid Hemorrhage and Ruptured Saccular Aneurysms
 "The worst headache I've ever had"
 Most common cause is rupture of saccular ("berry") aneurysm in a cerebral artery
 90% found near major arterial branch points in anterior circulation
 Structural abnormality of involved vessel = absence of SM and intimal elastic lamina
 1.3% will rupture per year, but chances up to 50% in larger aneurysms
 Ruptures associated w/ acute incidence of intracranial pressure (sexing or pooping)
 Comes with risk of vasospasm due to vessels being bathed in extravasated blood
o Vascular Malformations
 Classified into (1) arteriovenous, (2) cavernous, (3) capillary telangiectasis, (4) venous angiomas
 (1) and (2) are associated w/ risk of hemorrhage and development of symptoms
 Arteriovenous malformations
 Vessels in subarachnoid space and/or brain
 Arteriovenous shunting in tangled network for wormlike vascular channels
 Often show evidence of prior hemorrhage
 Results in seizure disorder, intracerebral hemorrhage, or subarachnoid hemorrhage
 Most common site is middle cerebral artery (esp. posterior branches)
 Cavernous malformations
 Distended, loosely organized vascular channels
 Usually no brain parenchyma between vessels
 Occur most often in cerebellum, pons, and subcortical regions
 "Low-flow" channels > do not participate in arteriovenous shunting
 Vessels often surrounded by old hemorrhage, infarction, and calfication
 Familial forms are common > highly penetrant autosomal dominant trait