patoloji-ders-notlari

Title

Serdar Balcı

Cerebrovascular diseases

Serdar BALCI, MD

EDEMA, HERNIATION, AND HYDROCEPHALUS

Central Nervous System

Rigid skull and spinal canal
Specific foramina
- vessels and nerves pass
Advantage of protection
But cannot expand
- generalized cerebral edema, hydrocephalus, mass lesions, tumors

EDEMA

Cerebral Edema

Accumulation of excess fluid within the brain parenchyma
Vasogenic edema
- Integrity of the normal blood-brain barrier is disrupted
- Fluid shift from the vascular compartment into the extracellular spaces of the brain
- Localized
  - increased vascular permeability due to inflammation, tumors
- Generalized
Cytotoxic edema
- Increase in intracellular fluid
- Neuronal and glial cell membrane injury
- Generalized hypoxic-ischemic insult, exposure to some toxins

Edematous brain

Softer than normal

Appears to “over fill” the cranial vault

In generalized edema gyri are flattened, the intervening sulci are narrowed, and the ventricular cavities are compressed

Robbins Basic Pathology

Cerebral edema

Gyri are flattened as a result of compression of the expanding brain by the dura mater and inner surface of the skull. Such changes are associated with a dangerous increase in intracranial pressure.

Robbins Basic Pathology

HYDROCEPHALUS

Hydrocephalus

CSF is produced by the choroid plexus within the ventricles

Circulates through the ventricular system

Flows through the foramina of Luschka and Magendie into the subarachnoid space

Absorbed by arachnoid granulations

The balance between rates of generation and resorption regulates CSF volume

Robbins Basic Pathology

Accumulation of excessive CSF within the ventricular system
Overproduction of CSF
- Tumors of the choroid plexus
- Rarely causes hydrocephalus

Noncommunicating hydrocephalus
- Localized obstacle to CSF flow within the ventricular system
- A portion of the ventricles enlarges while the remainder does not
- Masses obstructing the foramen of Monro or compressing the cerebral aqueduct
Communicating hydrocephalus
- Entire ventricular system is enlarged
- Reduced CSF resorption
In infancy before closure of the cranial sutures, the head enlarges
Once the sutures fuse, hydrocephalus causes ventricular expansion and increased intracranial pressure, but no change in head circumference
Hydrocephalus ex vacuo
- A compensatory increase in CSF volume can also follow the loss of brain parenchyma after infarcts or with degenerative diseases

HERNIATION

Herniation

Cranial vault is subdivided by rigid dural folds
- falx and tentorium
Intracranial pressure rises
- Volume of tissue and fluid inside the skull increases beyond the limit permitted by compression of veins and displacement of CSF
Focal expansion of the brain displaces it in relation to these partitions
If the expansion is sufficiently large, herniation occurs
Herniation often leads to “pinching” and vascular compromise of the compressed tissue
- infarction, additional swelling, and further herniation

Robbins Basic Pathology

Subfalcine (cingulate) herniation

Unilateral or asymmetric expansion of a cerebral hemisphere displaces the cingulate gyrus under the edge of falx

Compression of the anterior cerebral artery

Subfalcial herniation

Autopsy Pathology: A Manual and Atlas

Transtentorial (uncinate) herniation

Medial aspect of the temporal lobe is compressed against the free margin of the tentorium
Temporal lobe is displaced
Third cranial nerve is compromised
- Pupillary dilation and impaired ocular movements on the side of the lesion (“blown pupil”)
Posterior cerebral artery may also be compressed
- ischemic injury
- primary visual cortex

If herniation is big enough
- compress the contralateral cerebral peduncle against the tentorium
- hemiparesis ipsilateral to the side of the herniation (false localizing sign)
Kernohan’s notch
- Deformation formed by compression of the peduncle

Transtentorial herniation

Autopsy Pathology: A Manual and Atlas

Duret hemorrhages

-Progression of transtentorial herniation

-Linear or flame-shaped hemorrhages in the midbrain and pons

-Lesions usually occur in the midline and paramedian regions

-Result of tearing of penetrating veins and arteries supplying the upper brain stem

Robbins Basic Pathology

Duret hemorrhage

Mass effect displaces the brain downward

Disruption of the vessels that enter the pons along the midline, leading to hemorrhage

Robbins Basic Pathology

Tonsillar herniation

Displacement of the cerebellar tonsils through the foramen magnum

Life-threatening

Brain stem compression

Compromises vital respiratory and cardiac centers in the medulla

Cerebellar tonsillar herniation

Autopsy Pathology: A Manual and Atlas

CEREBROVASCULAR DISEASES

Stroke

Stroke (İnme, Nuzül, Felç)
- clinical designation applied to all conditions when symptoms begin acutely
Thrombotic occlusion
Embolic occlusion
Vascular rupture
Thrombosis and embolism
- loss of oxygen and metabolic substrates
- infarction or ischemic injury of regions supplied by the affected vessel
complete loss of perfusion, severe hypoxemia (e.g., hypovolemic shock), or profound hypoglycemia
- global injury
Hemorrhage accompanies rupture of vessels
- direct tissue damage, secondary ischemic injury

HYPOXIA, ISCHEMIA, AND INFARCTION

Hypoxia

Brain is highly oxygen-dependent tissue
Requires a continual supply of glucose and oxygen from the blood
- 2% of body weight
- 15% of the resting cardiac output
- 20% of total body oxygen consumption
Cerebral blood flow auto-regulated for a stable blood pressure and intracranial pressure
Functional hypoxia
- Low partial pressure of oxygen
  - high altitude
- Impaired oxygen-carrying capacity
  - severe anemia, carbon monoxide poisoning
- Inhibition of oxygen use by tissue
  - cyanide poisoning
Ischemia
- Transient or permanent
- Tissue hypoperfusion
  - Hypotension
  - Vascular obstruction

Global Cerebral Ischemia

Widespread ischemic-hypoxic injury
Severe systemic hypotension
- systolic pressures <50 mm Hg
- cardiac arrest, shock, and severe hypotension
Neurons are more susceptible to hypoxic injury than glial cells
- Mild or transient global ischemic insults may cause damage to vulnerable areas
- Most susceptible neurons pyramidal cells of the hippocampus, neocortex and Purkinje cells of the cerebellum
Severe global cerebral ischemia
- widespread neuronal death irrespective of regional vulnerability
Macroscopically
- Brain is swollen
- Wide gyri and narrowed sulci
- Cut surface shows poor demarcation between gray and white matter

Early changes

12-24 hours after the insult

Acute neuronal cell change (red neurons)

Microvacuolization

Cytoplasmic eosinophilia

Pyknosis and karyorrhexis

Similar changes later in astrocytes and oligodendroglia

Early changes

12-24 hours after the insult

Acute neuronal cell change (red neurons)

Microvacuolization

Cytoplasmic eosinophilia

Pyknosis and karyorrhexis

Similar changes later in astrocytes and oligodendroglia

Reaction to tissue damage

Infiltration by neutrophils

Infiltration of a cerebral infarction by neutrophils begins at the edges of the lesion where the vascular supply is intact.

Robbins Basic Pathology

Subacute changes

24 hours-2 weeks

Necrosis of tissue

Influx of macrophages

Vascular proliferation

Reactive gliosis

By day 10, an area of infarction shows the presence of macrophages and surrounding reactive gliosis.

Robbins Basic Pathology

Repair

> 2 weeks

Removal of all necrotic tissue

Loss of organized CNS structure, and gliosis

Old intracortical infarcts are seen as areas of tissue loss with a modest amount of residual gliosis

Robbins Basic Pathology

Border zone (“watershed”) infarcts

Wedge-shaped areas of infarction

Regions of the brain and spinal cord that lie at the most distal portions of arterial territories

Seen after hypotensive episodes

Border zone between the anterior and the middle cerebral artery distributions is at greatest risk

Focal Cerebral Ischemia

Cerebral arterial occlusion
Focal ischemia
Infarction in the distribution of the compromised vessel
The size, location, and shape of the infarct and the extent of tissue damage that results may be modified by collateral blood flow
Collateral flow through the circle of Willis or cortical-leptomeningeal anastomoses can limit damage in some regions
There is little or no collateral flow to structures such as the thalamus, basal ganglia, and deep white matter
- supplied by deep penetrating vessels

Embolic infarctions

More common than infarctions due to thrombosis
Cardiac mural thrombi are a frequent source of emboli
Thromboemboli arise in carotid arteries or aortic arch
Middle cerebral artery
- direct extension of the internal carotid artery
- most frequently affected by embolic infarction
Emboli tend to lodge where vessels branch or in areas of stenosis, usually caused by atherosclerosis

Thrombotic occlusions

superimposed on atherosclerotic plaques

carotid bifurcation, the origin of the middle cerebral artery, and at either end of the basilar artery

accompanied by anterograde extension, as well as thrombus fragmentation and distal embolization

Infarcts

Nonhemorrhagic infarcts
- Acute vascular occlusions
- Treated with thrombolytic therapies
Hemorrhagic infarcts
- Result from reperfusion of ischemic tissue
- Through collaterals or after dissolution of emboli
- Often produce multiple, sometimes confluent petechial hemorrhages

Section of the brain showing a large, discolored, focally hemorrhagic region in the left middle cerebral artery distribution: Hemorrhagic (red) infarction

Robbins Basic Pathology

An infarct with punctate hemorrhages, consistent with ischemia-reperfusion injury, is present in the temporal lobe

Robbins Basic Pathology

Old cystic infarct shows destruction of cortex and surrounding gliosis

Robbins Basic Pathology

Macroscopic appearance of a nonhemorrhagic infarct

First 6 hours
- unchanged in appearance
48 hours
- pale, soft, and swollen
2-10 days
- brain turns gelatinous and friable
- boundary between normal and abnormal tissue becomes more distinct
- edema resolves in the adjacent viable tissue
10 day-3 week
- Tissue liquefies
- fluid-filled cavity lined by dark gray tissue
- gradually expands as dead tissue is resorbed
After first 12 hours
- ischemic neuronal change (red neurons)
- cytotoxic and vasogenic edema
- Endothelial and glial cells, mainly astrocytes, swell, and myelinated fibers begin to disintegrate
48 hours
- some neutrophilic emigration
2 to 3 weeks
- **mononuclear phagocytic cells **
Months to years
- Macrophages containing myelin or red cell breakdown products
Phagocytosis and liquefaction proceeds
Astrocytes at the edges of the lesion progressively enlarge, divide, and develop a prominent network of cytoplasmic extensions
After several months
- astrocytic nuclear and cytoplasmic enlargement regresses
Wall of the cavity, astrocyte processes form a dense feltwork of glial fibers admixed with new capillaries and a few perivascular connective tissue fibers
In the cerebral cortex, the cavity is delimited from the meninges and subarachnoid space by a gliotic layer of tissue, derived from the molecular layer of the cortex
The pia and arachnoid are not affected
- do not contribute to the healing process

The microscopic picture and evolution of hemorrhagic infarction parallel those of ischemic infarction

Addition of blood extravasation and resorption

INTRACRANIAL HEMORRHAGE

Intracranial Hemorrhage

Hypertension and other diseases leading to vascular wall injury
Structural lesions such as arteriovenous and cavernous malformations
Tumors
Subarachnoid hemorrhages
- caused by ruptured aneurysms
- vascular malformations
Subdural or epidural hemorrhages
- associated with trauma

Spontaneous (nontraumatic) intraparenchymal hemorrhages

Most common in mid- to late adult life
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
- brain hemorrhage 15% of deaths with chronic hypertension
- typically occur in the basal ganglia, thalamus, pons, and cerebellum

Cerebral hemorrhage. Massive hypertensive hemorrhage rupturing into a lateral ventricle

Robbins Basic Pathology

Acute hemorrhages

Extravasated blood
Compresses the adjacent parenchyma
With time, hemorrhages are converted to a cavity
- brown, discolored rim
Early lesions
- clotted blood
- anoxic neuronal and glial changes
- edema
Later
- edema resolves
- pigment- and lipid-laden macrophages appear
- proliferation of reactive astrocytes becomes visible at the periphery of the lesion
- Similar changes observed after cerebral infarction

Cerebral Amyloid Angiopathy

Amyloidogenic peptides deposit in the walls of medium- and small-caliber meningeal and cortical vessels
- Similar to those in Alzheimer disease
Rigid, pipelike appearance and stains with Congo red
Weakens vessel walls and increases the risk of hemorrhages
Distribution is different from hypertensive hemorrhages
- occur in the lobes of the cerebral cortex ( lobar hemorrhages )

Subarachnoid Hemorrhage and Saccular Aneurysms

The most frequent cause of clinically significant non-traumatic subarachnoid hemorrhage is rupture of a saccular (berry) aneurysm
Other causes of subarachnoid hemorrhage:
- vascular malformation
- trauma
- rupture of an intracerebral hemorrhage into the ventricular system
- hematologic disturbances
- tumors

Saccular Aneurysms

Rupture can occur at any time (Ebru Gündeş)
1/3 associated with acute increases in intracranial pressure
- even straining at stool, sexual orgasm, holding sneezing
Blood under arterial pressure is forced into the subarachnoid space
Patient is stricken with sudden, excruciating headache
- the worst headache I’ve ever had
Rapidly loses consciousness
25-50% of affected persons die from the first bleed
Recurrent bleeds are common
Prognosis worsens with each bleeding episode

90% of saccular aneurysms occur in the anterior circulation near major arterial branch points

multiple aneurysms exist in 20-30%

Robbins Basic Pathology

Increased risk of aneurysms in patients with autosomal dominant polycystic kidney disease
Genetic disorders of extracellular matrix proteins
1.3% of aneurysms bleed per year
>1 cm in diameter, 50% risk of bleeding per year
In the early period after a subarachnoid hemorrhage
- additional risk of ischemic injury from vasospasm of other vessels
Healing and the attendant meningeal fibrosis and scarring sometimes obstruct CSF flow or disrupt CSF resorption, leading to hydrocephalus

An unruptured saccular aneurysm is a thin-walled outpouching of an artery

Robbins Basic Pathology

Beyond the neck of the aneurysm no muscular wall and intimal elastic lamina

Aneurysm sac is lined only by thickened hyalinized intima

Adventitia covering the sac is continuous with parent artery

Rupture usually occurs at the apex of the sac, releasing blood into the subarachnoid space or the substance of the brain, or both

Robbins Basic Pathology

Other aneurysms

Atherosclerotic
- fusiform and most commonly involve the basilar artery
Mycotic, traumatic, and dissecting aneurysms
- in the anterior circulation
Nonsaccular aneurysms
- manifest with cerebral infarction
- vascular occlusion

Vascular Malformations

arteriovenous malformations

cavernous malformations

capillary telangiectasias

venous angiomas

Arteriovenous malformations

Most common vascular malformation
M:F=2:1
10-30 years age
seizures, an intracerebral hemorrhage, or a subarachnoid hemorrhage
Large AVMs in the newborn
- high-output congestive heart failure because of blood shunting from arteries to veins
Risk of bleeding, most dangerous type of vascular malformation
Multiple AVMs
- hereditary hemorrhagic telangiectasia
- Autosomal dominant
- Mutations affecting the TGFβ pathway

Arteriovenous malformation

İnvolve subarachnoid vessels extending into brain parenchyma

Or exclusively within the brain

Tangled network of wormlike vascular channels

Robbins Basic Pathology

Enlarged blood vessels separated by gliotic tissue

Previous hemorrhage

Vessels can be recognized as arteries with duplicated and fragmented internal elastic lamina

Marked thickening or partial replacement of the media by hyalinized connective tissue

Cavernous malformations

distended, loosely organized vascular channels

thin collagenized walls

without intervening nervous tissue

most often in the cerebellum, pons, and subcortical regions

low blood flow without significant arteriovenous shunting

Foci of old hemorrhage, infarction, and calcification frequently surround the abnormal vessels

Capillary telangiectasias

microscopic foci of dilated thin-walled vascular channels

separated by relatively normal brain parenchyma

most frequently in the pons

unlikely to bleed or to cause symptoms, and most are incidental findings

Venous angiomas (varices)

aggregates of ectatic venous channels

unlikely to bleed or to cause symptoms, and most are incidental findings

Hypertensive Cerebrovascular Disease

Hyaline arteriolar sclerosis of the deep penetrating arteries and arterioles
Supply the basal ganglia, the hemispheric white matter, and the brain stem
Affected arteriolar walls are weakened and are more vulnerable to rupture
Minute aneurysms ( Charcot-Bouchard microaneurysms ) form in vessels
- less than 300 µm in diameter
May cause massive intracerebral hemorrhage
Lacunes or lacunar infarcts
- small cavitary infarcts
- just a few millimeters in size
- most commonly in the deep gray matter (basal ganglia and thalamus), the internal capsule, the deep white matter, and the pons
- caused by occlusion of a single penetrating branch of a large cerebral artery
- Depending on their location silent or significant neurologic impairment
Rupture of the small-caliber penetrating vessels
- development of small hemorrhages
- resorb, leave slitlike cavity ( slit hemorrhage ) surrounded by brownish discoloration
Acute hypertensive encephalopathy
- associated with sudden sustained rises in diastolic blood pressure to greater than 130 mm Hg
- increased intracranial pressure
- global cerebral dysfunction
- headaches, confusion, vomiting, convulsions, and sometimes coma
- brain edema, with or without transtentorial or tonsillar herniation
- Petechiae and fibrinoid necrosis of arterioles in the gray and white matter may be seen microscopically

Vasculitis

Infectious arteritis of small and large vessels
- syphilis and tuberculosis
- opportunistic infections
  - aspergillosis, herpes zoster, CMV
Polyarteritis nodosa
- single or multiple infarcts throughout the brain
Primary angiitis of the CNS
- involving multiple small to medium-sized parenchymal and subarachnoid vessels
- chronic inflammation, multinucleate giant cells (with or without granuloma formation)
- destruction of vessel walls
- diffuse encephalopathy
- cognitive dysfunction