pathophysiology of stroke 2

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Pathophysiology of Stroke 2

Case Presentation

This presentation addresses the pathophysiology of stroke. The followingtopics will be addressed: 1. Conditions that inuence ischemic injury 2. Mechanisms of neuron death coagulation necrosis !s. apoptosis" #. Cerebral blood ow $. %ur!i!al of brain tissue &. 'eatures of hypotensi!e stroke

Pathophysiology of Stroke

Introduction

This brief presentation of pathophysiology of stroke re!iews conditions thatinuence ischemic injury( mechanisms of death of neurons coagulationnecrosis !s apoptosis"( cerebral blood ow and sur!i!al of brain tissue andfeatures of hypotensi!e stroke. )schemic penumbra and !iability of brain

tissue( and re*perfusion hemorrhage * a complication of restoration ofcerebral blood ow to injured brain tissue are also e+plained.

,nderstanding of the pathogenesis of stroke is to understand how ischemiaand hemorrhage cause injury. -n ischemic stroke depri!es neurons of o+ygenand nourishment. -ccumulation of no+ious metabolites in the brain tissueoriginating from the injured or dying neurons increases with time( which thenresults in injury to the surrounding healthy neurons. This process can behalted or e!en re!ersed in the ischemic penumbral brain tissue if restorationof blood ow occurs within a critical time period. )n hemorrhagic stroke(

e+tra !ascular release of blood causes damage by cutting o connectingpathways( resulting in local or generali/ed pressure injury.

Two major types of 0strokes cause brain damage: ischemic andhemorrhagic stroke. )n ischemic stroke( which represents about 34 of totalstrokes( lack of circulating blood depri!es neurons of o+ygen andnourishment. The eects are fairly rapid because the brain does not store


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glucose and is incapable of anaerobic metabolism 1 . 5emorrhagic strokecauses damage to brain tissue by disrupting connecting pathways resultingin local or generali/ed tissue injury.

Acute Ischemic Injury

The occlusion of a major artery such as the middle cerebral artery is rarelycomplete and cerebral blood ow C6'" depends on the degree ofobstruction and the collateral circulation. The !ascular compromise leadingto an acute stroke is a dynamic process that e!ol!es o!er time and isinuenced by many factors 2*& .

These conditions inuence the progression and the extent ofischemic injury:

a" 7ate and duration: The brain better tolerates an ischemic e!ent

of short duration than a prolonged period of ischemia. 5owe!er( therate of de!elopment of ischemia also inuences the e+tent of ischemicinjury. - slow ischemic e!ent allows for collateral circulation to beestablished.

b" Collateral circulation: The impact of ischemic injury is greatlyinuenced by the state of collateral circulation in the aected area ofthe brain.

c" %ystemic circulation: -de8uate systemic blood pressure isre8uired to maintain cerebral perfusion.

d" Coagulation: -ny hypercoagulable state increases theprogression and e+tent of micro thrombi( e+acerbating !ascularocclusion.

e" Temperature: 9le!ated body temperature is associated withgreater ischemic injury

f" lucose: 6oth hyper or hypoglycemia ha!e deleterious eectson progression of ischemic injury.

Pathophysiology at acro tissue !e"el

The normal cerebral blood ow C6'" is appro+imately &3 to ;3ml


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is reduced to below 23 ml


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)schemic strokes can be grouped into three main categories: a" thrombotic(2" embolic and #" global ischemic hypotensi!e" stroke. The list of0infre8uent causes is !ery long. 5owe!er( strokes caused by !asospasmmigraine( following %-5( hypertensi!e encephalopathy" and some form of0arteritis stand out among the more infre8uent causes of stroke.

Throm#otic Stroke

-therosclerosis is the most common pathological feature of !ascularobstruction resulting in thrombotic stroke 2$ . Gther pathological etiologies of!ascular occlusion in thrombotic stroke are: clot formation due tohypercoagulable state( @bromuscular dysplasia( arteritis iant cell and Takayasu"( dissection of !essel wall and hemorrhage into a pre*e+istingpla8ue leading to an obstruction of the blood ow.

(m#olic Stroke

Most emboli lodge in the middle cerebral artery distribution because 34 ofthe blood carried by the large neck arteries end up in MC-. The two mostcommon sources of emboli are( the left* sided cardiac chambers and 0arteryto artery emboli D as in detachment of a thrombus from the internal carotidartery at the site of an ulcerated pla8ue. 9mbolic strokes are generallysmaller than thrombotic strokes.Many embolic strokes become 0hemorrhagic because ischemic tissue isoften reperfused when the embolus lyses spontaneously and blood ow isrestored to a pre!iously ischemic area.

*lo#al + Ischemic or ,ypotensi"e Stroke

?rofound reduction in systemic blood pressure for any reason is responsiblefor 0hypotensi!e stroke. Cerebral gray matter is particularly !ulnerable.lobal ischemia causes greatest damage to areas between the territories ofthe major cerebral and cerebellar arteries known as the boundary /one orwatershed area. The parietal*temporal*occipital triangle at the junction of theanterior( middle and posterior cerebral arteries is most commonly aected.

>atershed infarct in this area causes a clinical syndrome consisting ofparalysis and sensory loss predominantly in!ol!ing the arm. 'ace is notaected and speech is spared.

Selecti"e -ulnera#ility of 'eurons to *lo#al Ischemia


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%ome neurons are more susceptible to ischemia than others. These includethe pyramidal cell layer of the hippocampus and the ?urkinje cell layer of thecorte+. The increased susceptibility is due to an abundance of theneurotransmitter glutamate found in these neurons( which triggers thee+citoto+icity reaction discussed earlier 21 .

Complications of .estoration of /lood Supply to a Pre"iouslyIschemic Area

Two main complications of restoring blood supply are hemorrhage andcerebral edema. -n initial !ascular obstruction is likely to occur at abifurcation of a major !essel. The occlusion may obstruct one or both of thebranches( producing ischemia of the distal tissue. 6lood !essels as well asbrain tissue are rendered fragile and injured. >hen the occluding emboluseither lyses spontaneously or breaks apart and migrates distally( C6' isrestored to the 0injured or ischemic arterioles. This can result in a

hemorrhagic or 0red infarct in what had pre!iously been a bloodless @eld. The areas that continue to be poorly perfused are referred to as 0anemicinfarcts 2&=2; . The following factors are associated with 0red infarcts or a hemorrhagictransformation of stroke:

a" %i/e of the infarct. The bigger the infarct( the greater the possibility

of hemorrhage.b" 7ichness of collateral circulation.c" The use of anticoagulants and inter!entional therapy with

thrombolytic agents is associated with a higher incidence of

hemorrhagic transformation. Hasogenic edema follows loss of cerebral autoregulatory mechanisms inischemic areas of the brain. Iarge infarcts are associated with a greaterpotential of de!eloping cerebral edema. ?ost ischemic brain edema peaks at$ to E2 hours after the onset of symptoms 2E .


.eferences

1. Jones T5( Morawet/ 76( Crowell 7M( et al: Thresholds of focal cerebral

ischemia in awake monkeys. Journal of Neurosurgery 11=&$:EE#*E2.


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2. >ass CT( Ianier >I: lucose modulation of ischemic brain injury:re!iew and clinical recommendations. K7e!iewL K13 refsL. MayoClinic Proceedings 1;=E1:31*12.

#. 6runo -( 6iller J( -dams 5?( et al: -cute blood glucose le!el and

outcome from ischemic stroke. Trial of G7 131E2 in -cute %troke Treatment TG-%T" )n!estigators. Neurology 1=&2:23*2$.

$. 7eith J( Jorgensen 5%( ?edersen ?M( et al: 6ody temperature in acutestroke: relation to stroke se!erity( infarct si/e( mortality( andoutcome. Ksee commentsL. Lancet 1;=#$E:$22*$2&.

&. %chwab %( %pranger M( -scho -( %teiner T( 5acke >: 6raintemperature monitoring and modulation in patients with se!ereMC- infarction. Neurology 1E=$:E;2*E;E.

;. ?ulsinelli >-: )schemic ?enumbra in %troke. Sci Med 1&=1:1;*2&.

E. 5akim -M: )schemic penumbra: the therapeutic window. K7e!iewL K21refsL. Neurology 1=&1:%$$*%$;

. -strup J( %iesjo 6( %ymon I: Thresholds in cerebral ischemia * theischemic penumbra. Stroke 11=12:E2#*E2&.

. Ni!in J-( Choi F>: %troke therapy. Scientic American 11=2;&:&;*;#.

13. >ise 7J( 6ernardi %( 'rackowiak 7%( Iegg BJ( Jones T: %erial obser!ationson the pathophysiology of acute stroke. The transition from

ischaemia to infarction as reected in regional o+ygene+traction. Brain 1#=13;:1E*222.

11. 5eros 7C: %troke: early pathophysiology and treatment. %ummary of the'ifth -nnual Fecade of the 6rain %ymposium. KseecommentsL. Stroke 1$=2&:1EE*11.

12. 5ossmann -: Hiability thresholds and the penumbra of focal ischemia.Ksee commentsL. K7e!iewL K2 refsL. Annals ofNeurology 1$=#;:&&E*&;&.

1#. %iesjo 6( -gardh CF( 6engtsson ': 'ree radicals and brain damage.K7e!iewL K23& refsL. Cerebrovascular & Brain Metabolismevie!s1=1:1;&*211.

1$. del Noppo J( %chmid*%chonbein >( Mori 9( Copeland 67( Chang CM:?olymorphonuclear leukocytes occlude capillaries following middlecerebral artery occlusion and reperfusion inbaboons. Stroke 11=22:12E;*12#.


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1&. %iesjo 6: Cell damage in the brain: a speculati!e synthesis. K7e!iewLK2$$ refsL. Journal of Cerebral Blood "lo! &Metabolism11=1:1&&*1&.

1;. 7othman %MGJ>: 9+citoto+icity and the BMF- 7eceptors. #rends in

Neuroscience 1E=13:2*#32.

1E. 6ecker J: )nammation and acute stroke. K7e!iewL K;; refsL. Current$%inion in Neurology 1=11:$&*$.

1. 5ademenos J( Massoud T': 6iophysical mechanisms of stroke.K7e!iewL K$& refsL. Stroke 1E=2:23;E*23EE.

1. Feraba TJ: The role of inammation after acute stroke: utility ofpursuing anti*adhesion molecule therapy. K7e!iewL K;#refsL. Neurology 1=&1:%;2*%;

23. roemer ( ?etit ?( Nam/ami B( Hayssiere JI( Mignotte 6: Thebiochemistry of programmed cell death. K7e!iewL K$ refsL. "ASB Journal 1&=:12EE*12E.

21. arcia J5: Morphology of global cerebral ischemia. K7e!iewL K&2refsL. Critical Care Medicine 1=1;:E*E.

22. Choi F>: )schemia*induced neuronal apoptosis. K7e!iewL K&&refsL. Current $%inion in Neurobiology 1;=;:;;E*;E2.

2#. ajstura J( Cheng >( 7eiss ( et al: -poptotic and necrotic myocyte cell

deaths are independent contributing !ariables of infarct si/e inrats. Laboratory 'nvestigation 1;=E$:;*13E.

2$. Challa H: At(erosclerosis of t(e Cervicocranial Arteries( ?hiladelphia(Iippincott >illiams and >ilkins= 1:

2&. Iyden ?F( Ni!in J-: 5emorrhagic transformation after cerebral ischemia:mechanisms and incidence. K7e!iewL K;; refsL. Cerebrovascular &Brain Metabolism evie!s 1#=&:1*1;.

2;. Toni F( 'iorelli M( 6astianello %( et al: 5emorrhagic transformation ofbrain infarct: predictability in the @rst & hours from stroke onsetand inuence on clinical outcome. KseecommentsL. Neurology 1;=$;:#$1*#$&.

2E. 7opper -5( %hafran 6: 6rain edema after stroke. Clinical syndrome andintracranial pressure. Arc(ives of

Neurology 1$=$1:2;*2.


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Annotated /i#liography

01 /arnett ,enry 3 ohr 3P Stein / 4atsu 5 6eds7

Stroke Pathophysiology )iagnosis and anagement1 Thirdedition Philadelphia PA: Churchill !i"ingston8 099

This is one of the most e+hausti!e sources of all aspects of stroke. -!oluminous book of o!er 1$33 pages is di!ided into & sections. Thesection of pathophysiology has an e+cellent re!iew of neurochemistryand molecular biology. Two !ery useful chapters dedicated to functionalM7) and ?9T scans reference recent works which !alidate hypothesesregarding cerebral blood ow and o+ygen


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-poptosis is now known to occur in both global and focal ischemicinsults. This is a good re!iew of apoptosis.


Buestions

01 Conditions that ad"ersely inuence progression and extent of

ischemic injury include all of the follo%ing except

a. systemic hypotensionb. rapid de!elopment of an ischemic e!entc. 5ypercoaguable states

d. ?rolonged ischemiae. below normal body temperaturef. 5ypo or hyperglycemiag. %tate of collateral circulation 21 5eatures of ischemic stroke due to glo#al reduction in cere#ral

#lood o% 6,ypotensi"e stroke7 include all the follo%ing except

a. 5ippocampus and purkinje cell layer of the cerebral corte+ are most

!ulnerable to a reduction in cerebral blood ow

b. %peech diOculties typify !ictims of 5ypotensi!e stroke who reco!erc. ,ncontrolled release of e+citatory amino acids primarily glutamate and

aspartate cause calcium channels to open up which ultimately leads tocell death

d. %ites aected by critically low cerebral blood ow are located at theend of an arterial territory( the so*called watershed areas

=1 The true statement %ith regards to ischemic penum#ra 6IP7 is

a. )? is an area of massi!e neuronal death that results from a global

reduction in cerebral blood ow C6'"b. C6' in the )? is usually abo!e the &34 of the normc. -uto regulatory mechanisms are preser!ed in the )?d. )? is a potentially sal!ageable area of marginal blood ow that

surrounds a core of ischemic brain tissue

>1 All of the follo%ing are true except


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more of these underlying diseases or risk factors. The primary pathologies

include hypertension( atherosclerosis leading to coronary artery disease(

dyslipidemia( heart disease( and hyperlipidemia. The two types of stroke that

result from these disease states are ischemic and hemorrhagic strokes.

Bon*reducable 7isk 'actors

1. The possibilities of a stroke occurring increases with age. 'or e!ery

decade 13 years" o!er the age of &&( the possibility of a stroke

occurring doubles. - patient that is E& years of age has four times the

risk of ha!ing a stroke compared to someone who is && years old. Gf all

strokes that occur in people( appro+imately ;&4 occur in those who are

o!er the age of ;&.

2. Those who ha!e had a stroke or T)- are more likely to ha!e another

stroke or transient ischemic attack. -ppro+imately ;34 of strokes occur

in patients who ha!e had a pre!ious T)-.#. %trokes generally occur more often in males than females( until the

age of &&= after age && the risk is the same for both men and women.

$. The occurrence of stroke is higher in the -frican*-merican( 5ispanic(

and -sian*?aci@c )slander population than in other ethnical

backgrounds.

&. ?atients who ha!e immediate family members mother( father( or

sibling" that ha!e had a stroke or T)- are at greater risk for ha!ing a

stroke or T)- than those who do not ha!e a family history with these

e!ents.

;. ?eople who ha!e diabetes are also at greater risk of stroke that those

without diabetes.7educable 7isk 'actors

1. Iower your high blood pressure. 5ypertension high blood pressure" is

the number one most treatable risk factor for stroke. Rou can help

pre!ent a T)- or stroke considerably by working to lower your blood

pressure.

2. Iowering cholesterol le!els may decrease the risk of stroke. 6y working

to lower your cholesterol( you can help pre!ent a T)- or stroke.

#. %top smoking. )f you stop smoking( you can decrease your risk forstroke to that of a non*smoker within two to @!e years.

$. Management of heart disease and diabetes may also help to decrease

your risk of stroke.

pathophysiology of stroke 2

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