pathology of cerebral vascular disease

1. Dr. Emmanuel Morgan

2. Definitions:
Cerebrovascular disease: This term denotes any abnormality of the brain
caused by a pathologic process of blood vessels.
 Cerebrovascular diseases, from the clinical point of view, include three major
categories:
 Thrombosis,
 Embolism, and
 Hemorrhage;
Stroke: is the clinical designation that applies to all these conditions, particularly
when symptoms begin acutely

3. From the standpoint of pathophysiology and pathologic anatomy, it
is convenient to consider cerebrovascular disease as two processes:
Hypoxia, ischemia, and infarction resulting from impairment of blood
supply and oxygenation of CNS tissue
Hemorrhage resulting from rupture of CNS vessels


4. Types of hypoxia:
Stagnant hypoxia: decreased blood flow
Ischemic hypoxia (no flow)
Hypoxic hypoxia: reduced blood oxygen content (cardiopulmonary
disease)
Anemic hypoxia: reduced oxygen-carrying capacity (carbon
monoxide poisoning)
Histotoxic hypoxia: inability of tissues to use oxygen (cyanide
poisoning)
Hypoglycemic hypoxia: decreased ability to metabolize oxygen
under conditions of reduced blood glucose

5. The effects of hypoxia/ischemia depends on the following
factors:
The availability of collateral circulation,
The duration of ischemia, and
The magnitude and rapidity of the reduction of flow.

6. Two principal types of acute ischemic injury are
recognized:
Global cerebral ischemia occurs when there is a generalized
reduction of cerebral perfusion, such as in cardiac arrest, shock, and
severe hypotension.
Focal cerebral ischemia follows reduction or cessation of blood flow
to a localized area of the brain due to vessel occlusion (such as
embolic or thrombotic arterial occlusion)

7. Definition:
 An infarct is a circumscribed focus or area of brain tissue that was rendered
nonviable as a result of localized hypoxia-ischemia from cessation of blood flow
 Incidence:
 Accounts for 70% of all strokes
 Incidence: 70/100,000 persons between the ages of 45 and 55 years; 2/100
persons 85 years or older
Gender and Risk Factors:
 Male > female (highly dependent on risk factors)
Risk factors: diabetes, hypertension, smoking, family history, hyperlipidemia,
obesity

8. Causes of cerebral infarction:
In situ thrombosis
Embolism
Infectious vasculitis (toxoplasmosis, aspergillosis, and CMV
encephalitis)
Arteritis of small and large vessels (syphilis and tuberculosis)
Primary angiitis of the central nervous system
 Cerebral autosomal-dominant arteriopathy with subcortical infarcts
and leukoencephalopathy (CADASIL)
Cerebral amyloid angiopathy (CAA)

9. Embolism
 Origins and risk factors include
 Cardiac mural thrombi
 Myocardial infarct
 Valvular disease, and atrial fibrillation are important predisposing factors.
 Thromboemboli arising in arteries, most often originating over atheromatous
plaques within the carotid arteries.
 Paradoxical emboli
 Emboli associated with cardiac surgery; and
 Emboli of other material (tumor, fat, or air).

10. Clinical Features
Highly variable depending on
Amount of brain compromised
Location of the lesion
Duration of reduced flow
Status of collateral circulation
Intrinsic vulnerability of brain cells

11. Clinically, symptomatic patient my present with
Hemiplegia,
Sensory deficit,
Blindness,
Aphasia, or some other deficit.
The deficit evolves over time, and the outcome either is fatal or is
characterized by some degree of slow improvement during a period of
months

12. Recent infarct in the right
cerebral hemisphere.
The basal ganglia show
the features of
hemorrhagic infarction
(reperfusion injury).

14. Massive cerebral
infarct in an anterior
and middle cerebral
artery distributions
showing marked
mass effect and
midline shift

15. Cerebral infarction of several
years’ duration. The necrotic
tissue has been removed and
the ipsilateral lateral ventricle
is enlarged

16. Widespread white
matter hemorrhages
are characteristic of
bone marrow
embolization

17. Gross Findings
Acute cerebral infarct: focal swelling and congestion in a well-defined
vascular territory
 Subacute: circumscribed regions of congestion, softening, and early
cavitation with separation of cortex from the underlying white matter
 Chronic (remote) infarct: complete cavitation

18. Microscopic Findings
 Acute changes (12 to 24 hours after significant hypoxia-ischemia): tissue
pallor with acute neuronal necrosis eosinophilic (ischemic) cell change
 Subacute changes (2 days to 2 weeks): appearance of macrophages,
capillary proliferation, and early astrocytic reaction at the lesion edge
 Chronic changes (months to years): removal of necrotic tissue by
macrophages with resulting cavitation (liquefaction necrosis)

19.  Spontaneous (nontraumatic) intraparenchymal hemorrhages occur most
commonly in middle to late adult life, with a peak incidence at about age 60 years.
 Most are caused by rupture of a small intraparenchymal vessel.
 Most important causes includes
 Hypertension
 Coagulation disorders (hemorrhagic diathesis),
 Open heart surgery,
 Neoplasms,
 Amyloid angiopathy,
 Vasculitis,
 Fusiform aneurysms, and
 Vascular malformations.

20. Hypertension is the most common underlying cause of primary brain
parenchymal hemorrhage, accounting for more than 50% of clinically
significant hemorrhages.
 Hypertension causes a number of abnormalities in vessel walls, including
 Accelerated atherosclerosis in larger arteries;
 Hyaline arteriolosclerosis in smaller vessels;
 Minute aneurysms (Charcot-Bouchard microaneurysms)

21. Hypertensive intraparenchymal hemorrhage may originate in the
putamen (50% to 60% of cases), thalamus, pons, cerebellar
hemispheres (rarely), and other regions of the brain.
When the hemorrhages occur in the basal ganglia and thalamus,
they are designated ganglionic hemorrhages to distinguish them
from those that occur in the lobes of the cerebral hemispheres,
which are called lobar hemorrhages.

22. Lobar hemorrhages may arise in the setting of:
Hemorrhagic diathesis,
Infectious and noninfectious vasculitis, and
Cerebral amyloid angiopathy.
Trauma (rare)

23. Clinical Features
 Intracerebral hemorrhage can be clinically devastating when it affects large
portions of the brain and extends into the ventricular system,
 Or it can affect small regions and either be clinically silent or evolve like an infarct.
 Over weeks or months, there is a gradual resolution of the hematoma, sometimes
with considerable clinical improvement.
 Again, the location of the bleed will determine the clinical manifestations.

25. A, Massive
hypertensive
hemorrhage rupturing
into a lateral ventricle.
B, Hypertensive
hemorrhage in the
pons, with extension
to fill the fourth
ventricle.

26. The most frequent cause of clinically significant subarachnoid
hemorrhage is rupture of a saccular (berry) aneurysm.
Subarachnoid hemorrhage may also result from
Extension of a traumatic hematoma,
Rupture of a hypertensive intracerebral hemorrhage into the ventricular
system,
Vascular malformation,
Hemorrhagic diathesis, and
Tumors.

27. Saccular (berry) aneurysm (congenital aneurysm) is the most
common type of intracranial aneurysm.
 Other, rarer, types of aneurysms include
 Atherosclerotic (fusiform; mostly of the basilar artery),
 Mycotic,
 Traumatic, and
 Dissecting aneurysms.
 These latter three, like saccular aneurysms, are most often found in the anterior
circulation.
 They usually present with cerebral infarction rather than subarachnoid
hemorrhage.

28. Common sites of
saccular (berry)
aneurysms in the
circle of Willis.

29. Pathogenesis of Saccular Aneurysms
 The etiology of saccular aneurysms is unknown.
 Although the majority occur sporadically, genetic factors may be important in their
pathogenesis.
 There is an increased risk of occurrence among patients with certain heritable
disorders such as
 Autosomal-dominant polycystic kidney disease,
 Vascular type Ehlers-Danlos syndrome
 Neurofibromatosis type 1, and
 Marfan syndrome

30. A, View of the base of the
brain, dissected to show
the circle of Willis with an
aneurysm of the anterior
cerebral artery (arrow). B,
Dissected circle of Willis to
show large aneurysm. C,
Section through a saccular
aneurysm showing the
hyalinized fibrous vessel
wall (H & E).

31.  Clinical Features
 Rupture of an aneurysm with clinically significant subarachnoid hemorrhage is
most frequent in the fifth decade.
 Rupture may occur at any time but in about one-third of cases it is associated with
acute increases in intracranial pressure, such as with
 Straining at stool or
 Sexual orgasm.
 Blood under arterial pressure is forced into the subarachnoid space

32. Clinically patients are stricken with a
Sudden, excruciating headache, typically "the worst headache I've ever
had," and
Rapid lose of consciousness.
Between 25% and 50% of patients die with the first rupture, but most
patients who survive improve and recover consciousness in minutes.
Rebleeding is common in survivors, and it is currently not possible to
predict in which patients rebleeding will occur

33.  The clinical consequences of blood in the subarachnoid space can be separated
into
 Acute events, occurring in the hours to days after the hemorrhage, and
 Late sequelae associated with the healing process.
 In the early post-subarachnoid hemorrhage period, there is vasospasm and
increased risk of additional ischemic injury.
 In the late healing phase of subarachnoid hemorrhage, meningeal fibrosis and
scarring occur, sometimes leading to obstruction of CSF flow

34. There is a large
amount of fresh
haemorrhage in the
basal cisterns due
to rupture of an
aneurysm at the
upper end of the
basilar artery.

35. Vascular malformations of the brain are classified into four
principal groups:
Arteriovenous malformations,
Cavernous angiomas,
Capillary telangiectasias, and
Venous angiomas.

36. Clinical Features
Arteriovenous malformations are the most common type of clinically
significant vascular malformation.
Males are affected twice as frequently as females,
The lesion is often recognized clinically between the ages of 10 and 30
years, presenting as
A seizure disorder,
An intracerebral hemorrhage, or
A subarachnoid hemorrhage.

37. Arteriovenous
malformation:
There is a large
plexus of vascular
channels of
varying size in the
upper part of the
left cerebral
hemisphere.

38. The most important effects of hypertension on the brain include
Massive hypertensive intracerebral hemorrhage
Lacunar infarcts and
Slit hemorrhages, and
Hypertensive encephalopathy.
Atherosclerosis and diabetes are frequently associated diseases.

39. Acute hypertensive encephalopathy is a clinicopathologic syndrome
arising in a hypertensive patient characterized by diffuse cerebral dysfunction,
including
 Headaches,
 Confusion,
 Vomiting,
 Convulsions, and sometimes
 Coma.
 Rapid therapeutic intervention to reduce the accompanying increased intracranial
pressure is required, as the syndrome often does not remit spontaneously.

40. THANK YOU