8 PATHO6 - Cerebrovascular Disease 2015B(3)

6.8.2 CEREBROVASCULAR DISEASES Dr. Tilbe

CEREBROVASCULAR DISEASE 



Any abnormality of the brain due to an underlying pathology in the blood vessels  Impaired blood supply  rapidly developing loss of brain function. Clinically present as "Stroke” or CVA (cerebrovascular accident)

STROKE   

Medical emergency and can cause permanent neurological damage, complications, and death. Leading cause of adult disability in the US, Europe and even in the Philippines. No. 2 cause of death worldwide

TWO UNDERLYING PATHOLOGIC PROCESSES RESPONSIBLE FOR STROKE: 1) Impairment of blood supply of CNS tissue  hypoxia, ischemia, and infarction 2) Rupture of CNS vessels  hemorrhage  Impaired blood supply and hemorrhage will lead to ischemia (lack of glucose and oxygen supply)  Affected area is unable to function, leading to hemiplegia and other neurologic deficits COMMON CEREBROVASCULAR DISORDERS: 1) Thrombosis Ischemic stroke 2) Embolism 3) Intraparenchymal hemorrhage due to HPN Hemorrhagic 4) Subarachnoid stroke hemorrhage secondary to ruptured aneurysm A. Ischemic Stroke is due to a reduction of blood flow most commonly due to occlusion (an obstruction) brought about by thrombosis or embolism. B.

Hemorrhagic stroke (or intracranial hemorrhage)  due to rupture of blood vessel in the brain  spilling blood into the spaces surrounding the brain cells  due to rupture of cerebral aneurysm

Figure 2: Embolism may cause obstruction of CNS vessels resulting to death of brain tissue due to lack of blood supply.

CEREBRAL BLOOD FLOW  



 

 

CBF delivers a constant supply of glucose and oxygen Brain:  1- 2% of BW,  Receives 15% of the resting CO  Accounts for 20% of the total body O2 consumption. Normal CBF: about 50 mL/ minute for each 100 gm of tissue  regional variations between white and gray matter and among different portions of the gray matter CBF remains constant over a wide range of BP and ICP because of auto-regulation of vascular resistance. Causes of decreased oxygen to the brain:  A low partial pressure of oxygen (pO2) (functional hypoxia),  Impaired oxygen-carrying capacity of the blood,  inhibition of oxygen use by tissue  Ischemia after interruption of the normal blood flow. Special responses to ischemia in the CNS. Excitatory amino acid neurotransmitters (e.g. Glutamate) released  overstimulates and result in persistent opening of specific membrane channels including N-methyl-Daspartate and kainate receptors.  Cell death results from 1) Uncontrolled influx of calcium ions or 2) Toxic effects of nitrous oxide

 The mortality and long-term morbidity prognosis is generally worse for hemorrhagic strokes than for ischemic strokes.

Figure 1: Two processes in CVS: (1) Hypoxia, ischemia and infarction resulting from impairment of blood supply and oxygenation if CNS tissue. (2) Hemorrhage resulting from rupture of CNS vessels.

Mattus Medina Pamintuan Panday Parabuac Rejante

Figure 3: This diagram shows how the CNS responds to ischemia.

Page 1 of 6

TWO TYPES OF ACUTE ISCHEMIC INJURY A. GLOBAL CEREBRAL ISCHEMIA  Due to severe hypotensive episode leading to a generalized reduction of cerebral perfusion (cardiac arrest, shock, and severe hypotension.)  Clinical outcome: Diffuse hypoxic/ischemic encephalopathy: o Mild cases: no irreversible tissue damage  Eventual complete recovery o Severe cases: can result in irreversible damage to CNS tissue.  Occur in parts of the brain that lie at the boundary between zones of arterial distribution from different arteries.  Normally, border zones are hypoperfused because they are the last to receive blood from main arterial trunk.  With hypotension  watershed areas are more susceptible to damage than other areas of the brain.  PATHOLOGIC CONSEQUENCES:  Focal neuronal death that follows pattern of selective vulnerability. Preferentially affects Sommer Sector of Hippocampus and Purkinje cells  “Watershed infarcts”  Laminar necrosis

Figure 6: Gross picture of global cerebral ischemia. Brain is swollen. Gyri are widened, and the sulci are narrowed. Poor demarcation between gray and white matter. 

Microscopic Findings:  Mild global ischemia : neurons(most sensitive cells ) are affected first  Severe global cerebral ischemia: widespread neuronal death

B. FOCAL CEREBRAL ISCHEMIA/INFARCTION  Due to reduction or cessation of blood flow to a localized area of the brain  Focal ischemia: obstruction of local blood supplies not enough to cause necrosis.  Infarction: tissue necrosis due to sustained, obstruction of local blood supply (further discussed below); CAUSES: a) Large-vessel disease (such as embolic or thrombotic arterial occlusion) i. Thrombotic Arterial Occlusion - causes bland/white type of infarct ii. Embolic Arterial Occlusion - causes hemorrhagic type of infarct b) Small-vessel disease (such as vasculitis or occlusion secondary to arteriosclerotic lesions seen in HPN)

CEREBRAL INFARCTS  Figure 4: Bilaterally symmetric dark discolored areas (superior and just lateral to the midline) representing recent infarction in the watershed zone (overlapping area) supplied by ACA and MCA circulation 

CAUSES:

A. THROMBOTIC INFARCTS  

CORTICAL LAMINAR NECROSIS  A specific type of cortical infarction, which usually develops as a result of generalized ischemia  Typically affects the deep layers of the cerebral cortex (area receiving blood from blood vessels entering the cortex from the surface of the brain (“short penetrators”)

Focal brain necrosis due to complete and prolonged ischemia that affects all tissue elements



Are due to atherosclerosis The most common sites:  Carotid bifurcation,  the origin of the middle cerebral artery,  either end of the basilar artery. Frequently associated with hypertension and diabetes.

Figure 7: Majority of thrombotic occlusions is due to atherosclerosis.

Figure 5: Gross picture of laminar necrosis. The gray matter has six layers. The third layer is the most vulnerable to depletion of oxygen and glucose.

Mattus Medina Pamintuan Panday Parabuac Rejante

Page 2 of 6





Figure 8: Progressive narrowing of the lumen may be accompanied by embolization resulting to obstruction = stroke.

Figure 9: Thrombosis of the internal carotid artery (black arrow). B. EMBOLIC INFARCTS  Embolism is the most frequent cause of ischemic infarction.  Embolic infarcts have an abrupt onset.  Origin: 1) Cardiac mural thrombi are the most common sources. Predisposing factors: MI, valvular disease, and AF. 2) Thromboemboli arising in arteries, most often originating over atheromatous plaques within the carotid arteries. 3) Other sources: Emboli of other material (tumor, fat, or air). C. SMALL VESSEL DISEASE  Primarily seen in HPN and DM  Also known as:  "small artery arteriosclerosis",  "hyaline arteriolosclerosis”  "lipohyalinosis".  Pathogenesis:  HPN: endothelial injury and leakage of plasma proteins in and around vessels;  DM: glycation of pr- and diffuse BM thickening.  Vessels walls thicken, becomes homogenous and hyalinized  Lumen becomes narrowed  Vessels become tortous  Outcome:  SMALL INFARCTS (LACUNAR INFARCTS) which affects small penetrating arteries and arterioles that supply the BG, thalamus, deep white matter, and the BS  Account for about 20% of all strokes.  Single or multiple, small, cavitary infarcts

Mattus Medina Pamintuan Panday Parabuac Rejante

Due arteriolar sclerosis (due to HPN) of deep penetrating arterioles of Basal ganglia and brainstem. Maybe clinically silent or cause severe neurologic impairment depending on location.

Figure 10: Lakelike spaces (> fatal  Maybe clinically silent  May produce neurologic deficits o Hemorrhage may gradually resolve over weeks or months.

Figure 18: Cystic infarct showing destruction of the cortex with cavitation.

HEMORRHAGIC STROKES   

Accounts for 15% to 20% of strokes Due to rupture of blood vessels with intracerebral or subarachnoid hemorrhage. 3 major causes of hemorrhagic strokes are 1. Hypertensive bleed 2. Ruptured arterial aneurysms 3. Arteriovenous malformations

INTRACEREBRAL (INTRAPARENCHYMAL) HEMORRHAGE  Spontaneous (nontraumatic) intraparenchymal hemorrhages  Most common cause of hemorrhage in middle to late adult life  Most are caused by rupture of a small intraparenchymal vessel  Hypertension : the most common underlying cause ((Hypertensive Bleed) Accounts for more than 50% of clinically significant hemorrhages  Due to HPN induced vessel wall abnormalities:  Hyaline arteriolosclerosis in small vessels  Proliferative changes and frank necrosis of arterioles  Lipohyalinosis promoting the development of rupture prone Charcot-Burhard aneurysms

Figure 19: Massive hypertensive hemorrhage rupturing into a lateral ventricle. SUBARACHNOID HEMORRHAGE  Common cause of hemorrhagic stroke  Most common cause: rupture of a saccular (berry) aneurysm.  Other causes: Extension of a traumatic hematoma Rupture of a hypertensive intracerebral hemorrhage into the ventricular system, Vascular malformation, Hematologic disturbances Tumors  PATHOGENESIS OF SACCULAR ANEURYSMS Etiology: unknown. Majority occur sporadically Genetic factors may play a role in their pathogenesis. Predisposing factors:  Cigarette smoking  HPN Basic underlying defect: defect in the media of the vessel (maybe present since birth)

CHARCOT-BOUCHARD MICROANEURYSMS o Minute aneurysms, which are prone to rupture seen in patients with chronic HPN. o CB aneurysms, occur in vessels that are less than 300 μm in diameter o Most common within the basal ganglia. HPN: SLIT HEMORRHAGES  Slit-like cavity (slit hemorrhages) surrounded by brownish discoloration upon resorption  Due to rupture of the small-caliber penetrating vessels damaged by HPN.

Mattus Medina Pamintuan Panday Parabuac Rejante

Figure 19: Common sites of saccular aneurysm in the circle of willis.

Page 5 of 6

Figure 20: Berry aneurysm: Outpouchings (few mm - 3cm in diameter) at an arterial branch point along the circle of Willis. Have bright red shiny surface and a thin translucent wall. The wall or lumen may contain atheromatous plaques, calcification, or thrombus. 

SAH: Clinical Features: Most frequent in the 5th decade Slightly more frequent in females Aneurysms > 10 mm in diameter: 50% risk of bleeding per year. 1/3 cases it is associated with acute increases in intracranial pressure, such as with straining at stool or sexual orgasm. Sx: sudden, excruciating headache, then rapidly lose consciousness.



Complications of SAH: 1) Acute events ( hours to days)  Vasospasm  increased risk of further damage 2) Late sequelae  Meningeal fibrosis and scarring can lead obstruction of CSF flow.

  

Most common type of vascular malformation. M:F ratio 2:1 Clinically presents between the ages of 10 and 30 years as:  Seizure disorder  Intracerebral hemorrhage  Subarachnoid hemorrhage Most common site: territory of the MCA, particularly its posterior branches Developmental abnormalities of cerebral vessels. Tangle of abnormal vessels interposed between a feeding artery and a draining vein. Chronic compression  ischemia of brain tissue  seizures and neurologic deficits HISTO: Greatly enlarged blood vessels separated by gliotic tissue

Figure 22: Vascular malformation: dilated, tortuous, worm-like blood vessels separated by gliotic tissue

CEREBRAL EDEMA 

  

Caused by the release of osmotically active substances (arachidonic acid, electrolytes, lactic acid) from the necrotic brain tissue Vascular injury and leakage of proteins in the interstitial space aggravates edema By 3-4 days (most dangerous period for large infarct) interstitial fluid accumulates in the infarct and around it. Increase tissue volume ( edema or hemorrhage)  increase pressure inside fixed capacity of skull  damage to brain by:  Decreasing perfusion  Displace tissue across dural barriers or through openings (herniation)

ARTERIOVENOUS MALFORMATION

 

 

Figure 23: Swelling of the left cerebral hemisphere  a shift with herniation of the uncus of the hippocampus through the tentorium  uncal grooving (white arrow.)

Figure 24: Acute cerebral swelling producing herniation of the cerebelllar tonsils into the foramen magnum. Figure 21: GROSS morphology - tangled network of wormlike irregular, tortuous vessels with prominent, pulsatile arteriovenous shunt.



Acute brain swelling in the closed cranial cavity is serious can be fatal. Cause of death from a massive hemispheric infarct:  Cerebral edema and herniations --- End---

Mattus Medina Pamintuan Panday Parabuac Rejante

Page 6 of 6