Neuropathology Cerebrovascular Disease

Front 1

What is a cerebrovascular disease?

Back 1

A stroke or brain attack

Front 2

Describe stroke epidemiology
-How many people are killed by strokes every year in the US?
-How many people have strokes?
-How many stroke survivors are there?
-How many are impaired by stroke?
-How many will have another stroke within 5 years?

Back 2

-160,000 making it the third most common cause of death in the US
-Every year approximately 730,000 american have a new or recurrent stroke
-There are 4 million stroke survivors
-About 1/3 are mildly impaired, 1/3 are moderately impaired and the remainder are severely impaired
-One third will have another stroke within 5 years

Front 3

What is cerebrovascular disease?

Back 3

-Any abnormality of the brain parenchyma caused by pathologic alterations of blood vessels that supply and drain the CNS
-From a pathophysiologic and anatomic standpoint, it is convenient to consider cerebrovascular disease as processes that lead to infarction (encephalomalacia) or hemorrhage

Front 4

What are the two most important predisposing conditions for cerebrovascular disease?

Back 4

-Atherosclerosis
-Systemic hypertension

Front 5

What arteries supply the brain?

Back 5

-R and L internal carotid feeds the anterior circulation system
-Vertebral arteries feed the posterior circulation system

Front 6

What connects the anterior and posterior circulation?

Back 6

The circle of Willis around the pituitary stalk

Front 7

Describe how the internal carotids enter the skull

Back 7

-The floor of the middle cranial fossa and then make a cephalad and caudad hairpin turn as it passes through the cavernous sinus in the lateral margin of the sella turcica

Front 8

What does the anterior cerebral artery supply?

Back 8

The motor cortex responsible for the voluntary movement of the leg

Front 9

What does the middle cerebral artery supply?

Back 9

The motor cortex responsible for the voluntary movement of the arm and face

Front 10

What feeds the basal ganglia?

Back 10

Lenticulostriate arteries, which arise from the first segment of the middle cerebral artery

Front 11

Describe how the vertebral arteries enter the skull

Back 11

They enter the foramen magnum, run anteriorly on the ventral surface of the medulla, and come together at the junction with the pons to become the basilar artery.
-At the pontomesencephalic junction, the basilar bifurcates terminally into the R and L posterior cerebral arteries

Front 12

Where does the posterior circulation supply?

Back 12

-Occipital lobe
-Hippocampus
-Thalamus
-Most of the ventral surfaces of the hemispheres

Front 13

Describe the brains need for oxygen?

Back 13

-Brain comprises only 2% of body weight
-Requires 15% of cardiac output

Front 14

What is cerebral blood flow a function of?

Back 14

-Perfusion pressure (gradient between mean arterial pressure and venous pressure)
-Resistance of the vascular bed (determined mainly at the arteriolar level)

Front 15

What is the consequence of increased intracranial pressure on blood flow?

Back 15

Increased intracranial pressure raises venous pressure and, unless compensated for, lowere the perfusion gradient and the flow of blood

Front 16

Describe autoregulatory mechanisms for cerebral blood flow

Back 16

Overall cerebral blood flow is relatively constant over a broad range of arterial pressure due to autoregulatory mechanisms

Front 17

What affects cerebral blood flow?

Back 17

Not mediated by autonomic nervous system or endocrine influences

Mediated by:
-Oxygen tension
-pH
-Carbon dioxide tension

Possibly affected by:
-Oligopeptide neurotransmitters

Front 18

Describe the brains response to ischemia

Back 18

-Neuronal function ceases seconds after circulatory arrest
-Irreversible structural damage follows a few minutes later
-Pyramidal neurons in the hippocampus and the Purkinje neurons of the cerebellum are particularly vulnerable to ischemia
-Glial cells, especially astroglial and microglial, are more resistant to impaired circulation than nerve cells

Front 19

With brain infarction, what affects the amount of damage and the survival of tissue?

Back 19

-Duration of ischemia
-Availability of collateral circulation
-Magnitude and rapidity of the reduction of blood flow

Front 20

What are the two types of acute ischemic injury?

Back 20

-Global cerebral ischemia - occurs when there is a generalized reduction of cerebral perfusion, such as in cardiac arrest and severe hypotension

-Focal cerebral ischemia - When there is a reduction or stoppage of blood flow to a localized area of the brain. The resultant localized lesion is referred to as an infarct and the pathological process as infarction

Front 21

Describe encephalomalacia

Back 21

Within hours of irreversible injury, brain tissue becomes softer than normal

Front 22

When does liquifaction necrosis occur?

Back 22

When all the parenchymal elements die

Front 23

Describe the dissolution of cell structures

Back 23

-A gradual process
-Dead tissue is autolyzed
-Debris is ingested and digested by phagocytes
-These macrophages slowly leave the field
-Over a period of weeks and months, vacated spaces (microcysts) gradually grow larger
-Months later nothing remains of the infarcted region but a gross cavity

Front 24

Describe scars in the brain

Back 24

The wall of an ischemic cavity, where nerve cells nad oligodendrocytes may have succumbed but astrocytes survived the acute infarction, includes a network of elaborated astroglial cell processes (glial fibers) that make up the brain's puny version of scar formation.

Front 25

Describe secondary degeneration of neuronal processes at a distance from the site of injury

Back 25

Also known as Wallerian degenration

If the nerve cell dies, its dendritic arbor and its axons disintegrate
-If the axon dies, the myelin sheath breaks down in short order
-Example: Destruction of the motor cortex in the frontal lobe, therefore, leads to secondary degeneration of nerve fibers along the entire length of the lateral and ventral funiculi of the spinal cord
-Regeneration occurs transynaptically, orthogradely in some systems and retrogradely in others

Front 26

What is the most common cause of brain infarction?

Back 26

Atherosclerosis

Front 27

Where do atherosclerotic plaques tend to form?

Back 27

The internal carotid arteries at the bifurcation of the common carotid in the nect
The vertebral and basilar arteries
The supraclinoid segment of the internal carotid artery
The middle and posterior cerebral arteries
Proximal segments of major branches of the Circle of Willis
*These are all affected in the usualy segmental and eccentric fashion*

Front 28

What artery is usually not affected by atherosclerosis?

Back 28

The anterior cerebral artery past the anterior communicating artery

Front 29

What is characteristic of the most advanced cases of atherosclerosis?

Back 29

Thickening of the intimal layer of the cerebral convexities

Front 30

What are watershed zones? Why are they important to consider?

Back 30

-Areas of the brain bathed by the terminals of two different arteries
-When stenosis of an internal carotid reaches a certain point, circulation through the ipsilateral middle and anterior cerebral arteries is crtically compromised and the watershed areas are most vulnerable

Front 31

What is required/important for infarction?

Back 31

-Severe stenosis by an atherosclerotic plque
-Hemorrhage into the plaque
-Thrombus formation on the surface of hte plaque
-Systemic factors affecting cardiac rhythm and output are important
-Blood pressure is important
-Regional cerebral blood flow is important

Front 32

Describe laminar necrosis

Back 32

-Gray matter is usually more sensitive to ischemia than white matter
-Laminar necrosis of the scerebral cortex is a pattern of infarction in which some horizontal layers of the cortex, usually the middle or deeper ones, areseverely affected while te other layers are relatively spared
-The layer of predominantly astroglial tissue immediately beneath the pia and the ependyma usually resists destriction, undergoes florid hyperplasia, and walls off an area of cavity necrosis from subarachnoid and ventricular spaces
-The depths of cortical convolutions are often more severely damaged than the crests

Front 33

What are transient ischemic attacks?

Back 33

-Brief, recurrent episodes of focal neurological dysfunction, often remarkably repetitive in each patient
-A prelude to infarction
-May be caused by embolizing material dislodged from atheromatous plaques or tiggered by hemodynamic factors

Front 34

What is arteriolar sclerosis associated with?

Back 34

-Old age
-Hypertension at any age
-Diabetes mellitus

Front 35

How common is cerebral arteriolar sclerosis?

Back 35

About as common as its counterpart in the kidney, arteriolar nephrosclerosis

Front 36

What does arteriolar sclerosis cause?

Back 36

-It leads to small foci of infarctionn called, in their cystic end-stage, lacunes
-Most common in the basal ganglia, but they may be widely distributed in the brain

Front 37

Describe lacunar infarct

Back 37

-From arteriolar sclerosis
-Often hemorrhagic
-"Multilacunar state" is one of the causes of progresive dementia

Front 38

What is the pathogenesis of hemorrhagic lacunar infarcts?

Back 38

-There is development of microscopic aneurusms in the thickened walls of small intracerebral arteries in hypertensive individuals that can rupture
-This may occur in larger arteries that penetrate the basal ganglia and a few other sites and may lead to intracerebral hemorrhages of hypertensive disease

Front 39

Describe arterial embolization

Back 39

-A sudden occlusive event
-Leads to neurologic symptims that begin abruptly and are maximal almost immediately
-Embolic infarction is frequently, but not always, hemorrhagic

Front 40

Where do small emboli lodge and what do they cause?

Back 40

Small emboli lodge in small arteries in the subarachnoid space and their branches and produce small infarcts in hte cortex and subcortical white matter - not unlike blood-borne metastatic tumors in the cerebral hemispheres, which are usually located superficially

Front 41

What is a hemorrhage?

Back 41

Sizable extravasation of blood under pressure that replaces parenchymal tissue and produces a hematoma

Front 42

What is a hemorrhagic infarct?

Back 42

Infarcted tissue peppered by tiny hemorrhages

Front 43

How does a fresh infarct become hemorrhagic?

Back 43

It becomes hemorrhagic when blood flow is reestablished through dilated and damaged blood vessels, attributed to the propensity of embolic material to lyse or fragment and move downstram hours or days after occluding a vessel.

Front 44

What happenes to pure thromboemboli?

Back 44

They tend to reabsorb completely

Front 45

What happened to mixed thromboemboli?

Back 45

They tend to be organized by infiltrating fibroblasts from the wall of the blood vessel and a new lumen gradually formed (recanalization)

Front 46

Where do most cerebral thromboemboli come from?

Back 46

The heart

Front 47

What are the common sources of thromboemboli from the heart?

Back 47

-Left atrium in association with atrial fibrillation
-From damaged endocardial surfaces of the left ventricle after acute myocardial infarction
-Vegetations on the mitral and and aortic valves in rheumatic, bacterial, and non-bacterial endocarditis

Front 48

What is a mycotic aneurysm?

Back 48

When an infected embolus causes an inflammatory reaction in the wall of the occluded artery and the infection can spill into the subarachnoid spece

Front 49

What is the problem with showers of emboli?

Back 49

They produce multiple infarcts and a confusing array of neurologic symptoms

Front 50

Describe the consequences of ulceration and dissection of atherosclerotic plaques

Back 50

These can give rise to emboli of mixed composition. Small thrombi also, particularly aggregates of platelets, may break loose from the turbulent surface of atherosclerotic plaques

Front 51

What type of emboli produce global cerebral dysfunction?Why?

Back 51

-Gas emboli
-Fat emboli

These emboli tend to be copious and numerous small intraperenchymal blood vessels become occluded

Front 52

Where do fat emboli come from?

Back 52

They arise from the marrow of fractured long bones, enter the venous system, and filter through the lung into the systemic circulation

Front 53

Where do air emboli come from?

Back 53

They are caused by injury to the lungs or by rapid ascent in aviation or deep sea diving (Caisson's disease)

Front 54

What is vasculitis?

Back 54

An inflammatory process in blood vessel walls that can produce infarction by swelling the wall and narrowing the lumen, by damaging the endothelial lining and inducing thrombosis, or by destroying the vessel wall (necrotizing vasculitis) giving rise to hemorrhage.

Front 55

What can cause cerebral vasculitis?

Back 55

-Autoimmune disorder (polyarteritis nodosa)
-May be incidental to an intracranial infection
-Bacteria that cause subacute or chronic meningitis (TB meningitis, meningovascular tertiary syphilis)
-Aspergillus, Phycomyces, and Candida commonly infiltrate blood vessels (Cryptococcus does not)

Front 56

What hematologic disorder can cause infarction in the brain?

Back 56

The ones affecting coagulability, viscosity, or oxygen-carrying capacity of blood. These include
-Leukemias
-Sickle cell disease
-Thrombotic thrombocytopenic purpura
-Polycythemia
-Disseminated intravascular coagulation
-Anticoagulant therapy

Front 57

What typically causes primary subdural and epidural hemorrhages

Back 57

Traumatic lesions

Front 58

What typically causes spontaneous hemorrhage in the brain parenchyma and subarachnoid space

Back 58

-Underlying cerebrovacular disease
-Trauma

Front 59

Describe intracerebral hemorrhage

Back 59

-Often massive and fatal
-Dismal consequence of chronic hypertension

Front 60

What are the common sites of intracerebral hemorrhage?

Back 60

-One of the sizable arteries that run deep in the basal ganglia s the lenticulostriate branches of the middle cerebral artery
-Less common sites of hypertensive hemorrhages are the corpus medullaris of the cerebellum and the brain stem (almost always the pons)

Front 61

What are the consequences of massive hemorrhage in the basal ganglia?

Back 61

Loss of consciousness - which would be unusual in the more common stroke on the basis of infarction

Front 62

Describe the mass effect of hypertensive hemorrhages

Back 62

The mass effect is immediate and surrounding brain swelling and pressure are more marked than with infarction

Front 63

What is the most prognositc factor in hypertensive hemorrhages?

Back 63

Even with optimal medical management, the most important prognostic factor remains the size of the hemorrhage

Front 64

How can hypertensive hemorrhages result in death?

Back 64

-Dissection of the hemorrhage into the ventricle is incompatible with life for more than a few hours
-Hypertensive hemorrhage in the cerebellum, secondary compression of vital centers in the brain stem is the main threat to survival and timely removal of the hematoma may prove effective

Front 65

Describe the end results of hypertensive hemorrhages

Back 65

-The damage from intracerebral hemorrhage is compounded by foci of hemorrhagic infarction surrounding the hematoma
-Slowly the blood is resorbed an survivors end up with a cavity outlined by ragged walls stain by blood pigments

Front 66

What is the major cause of arterial subarachnoid hemorrhage at the base of the brain or in the Silvian fissure?

Back 66

Rupture of a saccular/berry aneurysm at or near the circle of Willis

Front 67

What are the initial symptoms of a saccular/berry aneurysm?

Back 67

-Head pain, typically explosive
-Promptly followed by depression of consciousness of variable degree

Front 68

What does it mean to have focal neurological defects present after a saccular/berry aneurysm bleed?

Back 68

May indicate
-Compression of neural structures, sometimes in the tentorial notch
-The blow-out under arterial pressure has dissected into the substance of the brain

Front 69

Describe the morbidity of acute subarachnoid hemorrhage

Back 69

Related to the hemorrhage itself and to the high incidence of segmental spasm of the parent artery at and beyond the site of aneurysmal rupture and not infrequently of nearby arteries as well

Front 70

Describe the segmental spasm of the parent artery during acut subarachnloid hemorrhage

Back 70

-At and beyond the site of aneurysmal rupture
-Not infrequently of nearby arteries as well
-Delayed effect, not ususally seen during the first 48 hours after rupture
-Persists for days before it resolves spontaneously
-Spasm produces ischemia and may result in infarction
-Behavior of arterial spasm is unpredicatable
-A scond bleed in short order at the site of rupture is frequent
-The ideal time at which the defect should be repaired is not an easy surgical judgement

Front 71

Describe saccular aneurysms

Back 71

-Called congenital
-Rarely occur in young children
-Located at or near arterial junctions, particularly:
-Between the posterior communicating artery and the internal carotid or the posterior cerebral artery
-At the short anterior communicating artery
-At the first branching of the middle cerebral artery in the Sylvian fissure
-Have a fairly broad base of origin from the partent artery and a short nect
-Usually rupture near the dome where hte wall of the aneurysm is likely to be thinnest
-Devoid of elastica and smooth muscle, they are composed entirely of poorly cellular collagen

Front 72

What are giant aneurysms?

Back 72

-Probably saccular aneurysms that enlarge slowly by repeated internal thrombosis and repair without hemorrhaging
-Think, non-uniform walls
-Diameter of a few centimeters
-Become symptomatic as a tumor mass compressing adjacent structures

Front 73

Describe fusiform aneurysms

Back 73

Segmental distentions of severely atherosclerotic arteries, notabley the basilar or a vertebral artery, and are also called atherosclerotic aneurysms

Front 74

Describe arteriovenous malformations

Back 74

-Congeries of abnormally large arteries and veins
-Rupture is the second major cause of spontaneous hemorrhage
-Vessels are interconnected and shunt arterial blood directly into venous channels
-Vessel walls are of uneven thickness and composition
-Walls not proportional to the caliber of the lumen
-Located mainly in subarachnoid space
-Extend into cortex and sometimes white matter
-Undergo scloerising changes at an accelerated pace
-Neuronal generation, foci of encephalomalacia, and astroglial reaction and fibrosis in the intervening parenchyma is common

Front 75

Describe blood flow through arteriovenous malformations

Back 75

-Hemodynamically abnormal
-They thrombose, leak, or hemorrhage

Front 76

Describe the symptoms of arteriovenous malformations

Back 76

-Seizures, especially focal fits
-Less commonly headaches
-Do not appear until adolescence or early maturity
-Lesions may be silent for decades
-Small episodes of hemorrhage or ischemic parenchymal injury as well as aging vascular changes in the malformation are cumulatively responsible for the belated onset of symptoms
-Hemorrhage in subarachnoid space tends to be smaller than from a ruptured aneurysm
-Large malformations fed by more than one major artery are not easily corrected surgically