pathology

2. Cerebrovascular diseases
• Denotes any abnormality of the brain caused by a
pathologic process of blood vessels.
• It includes three major categories
1. Thrombosis
2. Embolism
3. Hemorrhage
• Consider it as two processes:
• Hypoxia, ischemia & infarction resulting from
impairment of blood supply & oxygenation of CNS
TISS
• Hemorrhage resulting from rupture of CNS vessels.

3. Cerebrovascular diseases
• Cerebrovascular disease – 3 rd most common cause of death – most common of all
CNS diseases
• Stroke = sudden and dramatic development of a focal neurological deficit due to a
vascular impairment
• 10% of all deaths in the U.S.
• 500,000 new victims each year
• mainly results from HTN, cerebral atherosclerosis, or both
• SYMPTOMS OF STROKE
1. sudden weakness or numbness of the face, arm, or leg on one side of the body
2. loss of speech, or difficulty in speaking or understanding speech
3. dimness or loss of vision, in one eye
4. unexplained dizziness
• TIAs = reversible focal neurological symptoms secondary to ischemia which last from
several seconds to

4. Cerebrovascular diseases: Hypoxia,
Ischemia & Infarction
• Cerebral blood flow (50ml per minute for each 100gram of
tissue) remain constant over a wide range of BP & intracranial
pressure becoz of autoregulation of vascular resistance.
• Brian may be deprived of O2 by several mechanism:
functional hypoxia in a setting of a low partial pressure of
oxygen ( pO2), impaired O2 carrying capacity of blood, or
inhibition of O2 use by tissue.
Ischemia : transient / permanent after interruption of normal
circulatory flow.
1. Reduction in perfusion pressure ( Hypotension)
2. Secondary to vessel obstruction.

5. Cerebrovascular diseases
Two types of acute ischemic injury:
1.Global cerebral ischemia ( ischemic/hypoxia
encephalopathy) occurs when there is
generalized reduction of cerebral perfusion. E.g.
cardiac arrest, shock & severe hypotension.
2.Focal cerebral ischemia.: reduction or cessation
of blood flow to a localized area of brain
due to large vessel disease ( thrombotic/embolic
occlusion) small vessel disease ( vasculitis)

6. Cerebrovascular diseases
• Outcome of severe hypotensive episode
produces Global cerebral ischemia varies with
severity of the insult.
• Mild cases:transient postischemic confusional
state, with eventual complete recovery, no
irreversible tissue damage.
• Severe cases: wide spread neuronal death
occurs. patients who survive: severe impaired
neurologically and deep comatosed.

7. Cerebrovascular diseases
• Brain death including persistent evidence of
diffuse cortical injury & brainstem damage
including absent reflexes & resp. drive, absent
cerebral perfusion.
• Mechanical ventilation: brain undergoes
autolytic process- soft disintegrated tissue
that does not fix well with formalin & stain
poorly with dyes _ so called respirator brain

8. Cerebrovascular diseases
• Global cerebral ischemia:
Brain is swollen,
gyri are widened,
sulci are narrowed.
• c/s poor demarcation b/w gray & white matter.

9. Global cerebral ischemia:
• HP changes:
Early changes: 12-24hrs
acute neuronal cell damage characterised by
microvacuolization, then eosinophilia of neuronal
cytoplasm & later nuclear pyknosis & karyorrhexis.
similar changes seen in astrocytes
,oligodendroglia.

10. Cells most susceptible to Global
cerebral ischemia
• Pyramidal cell of hippocampus ( sommer
sector)
• Purkinje cells of cerebellum
• Pyramidal cells in neocortex
• After acute injury reaction to tissue damage
begins with infiltration by neutrophils.

11. Global cerebral ischemia:
Subacute changes: 24hrs to 2wks
• Necrosis of tissue
• Influx of macrophages
• Vascular proliferation
• Reactive gliosis

12. Global cerebral ischemia:
Repair: >2weeks
• Removal of all necrotic tissue
• Loss of normally organised CNS structure
• Gliosis
• Pseudolaminar necrosis: in cerebral cortex,
neuronal loss & gliosis produce an uneven
destruction of neocortex with preservation of
some layers & involvement of others.

13. Global cerebral ischemia:
• Border Zone ( “Watershed”) infarcts: Wedge
shaped areas of infarction that occur in regions
of brain & spinal cord which lie at the most
distal fields of arterial irrigation.Seen after
hypotensive episodes.
• In cerebral hemispheres, border zone b/w
anterior & middle cerebral artery distribution
is at greater risk & produce a sickle-shaped
band of necrosis over the cerebral convexity.

18. Infarction From obstruction of local
blood supply ( focal cerebral ischemia)
Cerebral arterial occlusion may lead to focal
ischemia & infarction of a specific region of
CNS tissue within the territory of distribution
of the compromised vessel.

19. ARTERIALINFARCTION
• Pathophysiology
• Chief causes: embolism and thrombosis ( due to atherosclerosis)
• Factors contributing to infarction
1. Decreased O2 in blood
• reduced hemoglobin in blood
• hypoxemia
2. Decreased perfusion
• cardiac arrest, hypoTN, shock, pulmonary embolism
• venous stasis, CHF, Increased ICP
3. Altered composition of blood
• polycythemia, thrombotic thrombocytopenic purpura
• macroglobulinemia
• oral contraceptives, pregnancy, and puerperium

20. ARTERIALINFARCTION
• Misc. causes of infarction
1. Hypoglycemia
2. Vasculitis ( association with syphilis & TB,
opportunistic infections like toxoplasmosis,
aspergillosis, CMV)
3. Infection with local thrombosis or endarteritis
obliterans
4. Compression of vessels by tumors, aneurysm
5. PAN & other collagen vascular diseases
6. Drug abuse( Heroin, cocaine)

21. ARTERIALINFARCTION
• Major sources of emboli
1. Cardiac mural thrombi ( most common).
MI, valvular diseases & Atrial fibrillation
are main predisposing factors.
2. thromboembolism arising in arteries originating over
atheromatous plaque within carotid arteries.
3. Paradoxical emboli ( in children with cardiac anomalies)
4. Emboli asso. With cardiac surgeries.
5. Emboli of other material( tumor, fat or air.)
6. Peripheral vessels – rare because of entry into right side of
heart first.

22. Classification of Infarcts
I. According to type
• Anemic (Pale)
• Hemorrhagic (red)
II. According to site of involvement
• Cortical and subcortical
• Cortical only
• laminar necrosis
• granular atrophy
• White matter only – HTN etiology
• Basal Ganglia

23. ARTERIALINFARCTION
• Remember topographical features are determined by artery
of supply
• Size and extent of infarcts influenced by:
1. Site of the occlusion (the more proximal, the more extensive)
2. presence and efficacy of collateral circulation ( major source
of collateral flow is the circle of willis.)
3. rapidity of occlusion (the more rapid, the more extensive)
• Two main types of infarcts
1. infarcts of end-arterial zones
2. boundary zones (water-shed) infarcts

25. ARTERIALINFARCTION
Common sites of thrombosis
• Carotid bifurcation
• Origin of MCA
• Either end of basilar artery.

26. ARTERIALINFARCTION
• CADASIL ( Cerebral autosomal- dominant
arteriopathy with subcortical infarcts &
leukoencephalopathy)
• Rare hereditary form of stroke caused bt
mutations in Notch3 gene.
• Characterized clinically by recurrent strokes
( usually infarcts ,less often hemorrhages) &
dementia.

27. ARTERIALINFARCTION
Cerebral amyloid angiopathy ( CAA):
• Amyloidogenic peptides deposit in the wall of
medium & small caliber meningeal & cortical
vessels .
• Weakning of vessel wall & risk of
hemorrhage.

28. Intracerebral( intraparenchymal)
hemorrhage
• Spontaneous (nontraumatic) intraparenchymal
hemorrhage occur most commonly occur in middle to
late adult life.
• Peak incidence: age 60 yrs
Cause:
• Rupture of a small intraparenchymal vessel
• HT :most common underlying cause of primary brain
parenchymal hemorrhage accounting for 50%)
• Brain hemorrhage accounts for 15% of deaths in
patients with Chronic HT.

29. Intracerebral( intraparenchymal)
hemorrhage
HT causes number of changes in vessel wall:
• Accelerated atherosclerosis in larger arteries.
• Hyaline arteriosclerosis in small vessel
• Severe form: Proliferative changes & frank necrosis
of arterioles
Chronic HT:
• Asso. with minute aneurysms, termed Charcot-
Bouchard microaneurysms which may be the site of
rupture. Most frequently found in the small arteries
of the basal ganglia.

30. Intracerebral( intraparenchymal) hemorrhage
5 Sites of HTN hemorrhage
1. Putamen ( 50 -60%)
2. Cerebral hemispheric white matter
3. Thalamus
4. Pons
5. Cerebellar white matter
• the location and relative incidence of HTN
hemorrhages is in accord with the distribution of
Charcot-Brouchard aneurysms
• Complications of HTN: rupture into ventricles or
through cortex into leptomeninges.

31. Intracerebral( intraparenchymal)
hemorrhage
• Ganglionic hemorrhages :when hemorrhage occur in basal
ganglia & thalamus.
• Lobar hemorrhages: occurring in lobes of cerebral
hemisphere. Arise in setting of hemorrhagic diathesis,
neoplasms, drug abuse, infectious & noninfectious vasculitis
& cerebral amyloid angiopathy.

32. Lobar hematoma

33. Brainstem (pontine) hemorrhage

34. Thalamic hematoma

35. Intracerebral( intraparenchymal)
hemorrhage
• Acute hemorrhages: Extravasation of blood with
compression of adjacent parenchyma.
Microscopy: central core of clotted blood surrounded
by a rim of brain tissue showing anoxic neuronal &
glial changes & odema.
• Old hemorrhages: area of cavitary destruction of
brain with a rim of brownish discoloration.
Microscopy: Odema resolves, pigment & lipid-laden
macrophages ,proliferation of reactive astrocytes at
the periphery.

36. Subarachnoid Hemorrhageand
ruptured Saccular Aneurysms.
Subarachnoid Hemorrhage: cause
• Rupture of a saccular( berry) aneurysm.
• Extension of atraumatic hematoma
• Ruptureof hypertensiveintracerebral
hemorrhageinto ventricular system,
• Vascular malformations,
• Hematological disturbances
• Tumors

38. Saccular or “berry” aneurysms
/congenital aneurysms
• Unruptured Saccular or “berry” aneurysms :
thin-walled outpouching at an arterial branch point
along circle of wills or a major vessel just beyond.
• Measure a few mm to 2-3cm in diameter.
• Bright red, shiny surface, thin, translucent wall.
• Atherosclerotic plaques, calcification, or thrombotic
occlusion of sac may be found in the wall or lumen of
aneurysm.
• Rupture occur at the apex of the sac.
• Other aneurysms: atherosclerotic, mycotic, traumatic
& dissecting aneurysms.

39. Saccular or “berry” aneurysms/congenital aneurysms
• clinically most relevant
Pathogenesis
• medial muscular defect (congenital)
• degeneration due to hemodynamic stress
• Rupture in 65% with subarachnoid and intracerebral
hemorrhage
• “The worst headache of my life!”
• MAY FORM MASS – DON’T BIOPSY
• may be further complicates by arterial spasm – which may
lead to thrombotic infarction
• treat these patients with Ca2+ CHANNEL BLOCKERS
prophylactically

40. Saccular or “berry” aneurysms
/congenital aneurysms
• most common locations of saccular
aneurysms
1. anterior communicating artery (30%)
2. middle cerebral artery (30%)
3. internal carotid artery and its branches (35%)
4. basilar artery bifurcation and vertebral artery
(5%)

41. Berry Aneurysms

42. Berry Aneurysms

43. Berry Aneurysms

45. Vascular malformations
Arteriovenous Malformation (AVM)
• large vascular spaces with intervening brain
• most common of all the vascular congenital abnormalities in neurosurgical
specimens
• clinical manifestations
1. Hemorrhagic stroke
2. Convulsions
• more than 90% supratentorial
• 10% of subarachnoid hemorrhages are caused by AVMs
Venous Angiomas
Cavernous angiomas
• veins are back-to-back
• no intervening brain
• slower flow of blood and become calcified and thrombosed
Capillary talangiectases

46. Schematic
drawing of AVM
Angiography

47. Hypertensive Cerebrovascular
Disease
1. Massive intracerebral hemorrhage
2. Lacunar infarcts
3. Slit hemorrhages
4. Hytensive encephalopathy

48. Hypertensive Cerebrovascular Disease
• Lacunar stroke or lacunar infarct (LACI) is a type
of stroke that results from occlusion of one of the
penetrating arteries that provides blood to the brain's
deep structures
• Basal ganglia, hemispheric white matter & brain stem
• Single or multiple, small, cavitary infarcts- lacunes
or lacunar state
• Lake like spaces, < 15mm wide, occur in lenticular
nucleus ,thalamus, internal capsule, deep white
matter, caudate nucleus & pons.
• Microscopy: loss of tissue, fat-laden macrophages &
gliosis

49. Lacunar infarct

50. Lacunar infarct

52. Slit hemorrhage

53. Hypertensiveencephalopathy
• presents with alterations of consciousness and
severe headaches
Pathological findings
• fibrinoid necrosis of arterioles
• edema
• Failure of vascular autoregulation and forced
opening of the BBB by sudden or prolonged
HTN

54. Hypertensiveencephalopathy
• Binwanger’s disease (subcortical arteriosclerotic encephalopathy)
• clinical picture
 persistent HTN
 systemic vascular disease
 history of acute strokes
 multifocal neurological symptoms
 long latent periods
 lengthy clinical course
 dementia
 ventricular dilatation
• Pathological findings
 diffuse degenration of white matter associated with multiple infarcts
• Numerous white matter lesions seen on the MRI of a demented patient w/
HTN should suggest Binswanger’s disease

55. THANK YOU