Ischemic Stroke Pattern And Pathogenesis Study In Patients With Symptomatic MCA Occlusive Disease

Internal carotid atherosclerosis is the most common cause of ischemicstroke in western population. However, atherosclerosis stenosis ofintracranial large artery occurs frenquently in stroke patients in Asia,especially the middle cerebral artery (MCA). Therefore, it's important tofind the patients with asymptomatic MCA occlusive disease for strokeprevention and treatment. Transcranial Doppler(TCD) can detect extra-andintra-cranial artery occlusive diseases and may be used as a noninvasivestool to screen risk individuals for stroke . Up to date, it's still controversyabout TCD accuracity in China due to absence of TCD diagnosis criteria.Otherwise, acute MCA total occlusion frenquently result from the carotidartery disease or cardiac embolus. However, the pattern and mechanism ofcerebral infarctions in MCA atherosclerotic stenosis(cerebral middle arteryocclusive disease, MCAOD) remain unknown. Possible pathogenesis forcerebral infarctions includes thrombosis, artery-artery embolism,hemodynamic impairment and MCA branch occlusion or combination ofthese factors. The elucidation of mechanism responsible for cerebralinfarctions may have clinical complications for treatment and prevention ofischemic stroke.Using the advantage of diffusion-weighted magnetic resonanceimaging(DWI) and TCD, we study stroke pattern and the relationshipbetween MCA atherosclerosis plaque and infartion.1. Optimal values of flow velocity on transcranial Doppler in diagnosingand grading middle cerebral artery stenosis in comparison with magneticresonance angiographyObjective: The aim of this study was to evaluate the best cutoff pointsof flow velocity for diagnosing and grading MCA stenosis compared withMRA in a large group of asymptomatic patients.Methods: We diagnosed 148 MCA stenostic patients withconventional method using EME-TC2000 TCD by a single researchtechnician. All patients performed a MRA within 1 week after TCDexamination. The severity of MCA stenosis was categorized asnormal-mild(<50%), moderate(50-75%), and severe(>75% and void offlow signal) on the basis of the amount of signal loss and the lumenreduction of MCA in MRA. According to different systolic velocity asfollowing ≥130 cm/s, ≥140 cm/s, ≥150 cm/s, ≥160 cm/s, ≥ 170 cm/s, wedrown different ROC(receiver operator characteristic) curve anddetermined which cutoff point was the best for diagnosing and grading ofMCA stenosis.Results: The numbers of vessel with normal, moderate and severestenosis were 75(25%), 112(38%), 109(37%) respectively in MRA, theirmean MCA velocity was 121.83 cm/s±22.52 cm/s, 155.96 cm/s±21.62 cm/s,199.39±43.86 cm/s respectively in TCD, there is an obvious difference ofsystolic velocity among three groups. Through calculating the bigest areasunder ROC(receiver operator characteristic), we concluded that the optimalcutoff points for diagnosing MCA stenosis was 140 cm/s(areas under ROCwas 0.87, P<0.001), and the specificity and sensitivity diagnosing MCAstenosis was 82.7%, 91.4% respectively . The optimal cutoff points forgrading MCA stenosis were 140 cm/s and 180 cm/s throughCHAID(chisquare automatic interaction dector) method.Conclusions: There are a good correlation between TCD and MRA indiagnosing and grading asymptomatic MCA stenosis. But it's difficult toaccurately locate stenosis position.2. Stroke pattern of FLAIR imaging and diffusion-weighted imaging inpatients with middle cerebral artery occlusive diseaseObjective: In ICA disease both emboli and hemodynamic mechanismare assumed to be the causes of stroke, studies based on CT have suggestedthat hemodynamically significant stenosis or occlusion of the extracranialICA may cause hemodynamic changes in the distal regions of thehemispheric blood supply, the so-called border-zones between majorvascular territories, while embolism from ICA stenosis is believed to affectthe middle cerebral artery stem and distal branches producing territorialinfarction. Atherosclerotic narrowing of the intracranial vessels is awell-recognized cause of cerebral ischemia in Chinese and about 1/2patients with ischemic stroke associated with middle cerebral arteryocclusive diseases(MCAOD). But the definite pathomechanism ofsymptomatic MCAOD is still not understood. Using FLAIR MRI and DWMRI, We investigated the lesion patterns on MRI FLAIR and DWI in acutestroke patients with symptomatic, unilateral MCAOD associated with astenosis >50% and analyze the relationship between stroke pattern and thedegree of MCA stenosis and further to undertand pathogenesis of stroke inpatients with MCAOD.Methods: we prospectively studied 238 acute ischemic stroke patientswith middle cerebral artery occlusive disease(MCAOD) detected bytranscranial Doppler(TCD) and/or magnetic resonance angiogram (MRA),MCAOD were divided into middle-grade and high-grade depending onMCA peak flow velocity and signal loss of MRA. All patients performedfluid-attenuated inversion recovery(FLAIR) sequence MRI, and partialpatients took diffusion-weighted(DW) MRI again. According to lesion size,site and distribution, acute infarction pattern on DWI were categorized ascortical territory infarction, border zone infarction and perforating arteryinfarction, they were further divided into MCA stem infarction, corticalbranch infarction, cortical multiple small infarction and centrum semiovaleinfarction, border zone infarction, striatocapsular infarction(giant lacunae)and lacunae-like infarction. Otherwise, Characteristics of infarction onDWI were divided into single infarction and multiple infarction dependenton the number of lesion on DWI. Then statistical analysis was done withSAS 6.12 version software.Results: 238 patients performed FLAIR MRI scan, results showed137(57.6%) patients with single lesion and 101(42.4%) patients withmultiple infarctions. Among of them, 82(34.5%) patients showed corticalterritory infarcts, 120 cases(50.4%) for deep small infarcts and border zoneinfarcts were 143(60.1%) patients, internal border zone(IBZ) infarction wasthe most common infarction pattern(52.9%), they were characterized bychainlike distribution in the paraventricular white matter, usually involvingcentrum semiovale and anterior border zone. For single infarction,striatocapsular infarction or giant lacunae were characteristic infarctionsubtype in MCA stem stenosis. Although patients with different stages ofMCAOD may present any stroke pattern or subtype, in statistic terms theincidence of a particular stroke pattern is clearly dependent on the degreeof stenosis, the patients with MCA stem total occlusion and severe stenosisare susceptive to had cortial branch infarction and centrum semiovaleinfarction, lacunae-like infarct occur in the patients with middle-gradestenosis. DWI results in 84 MCAOD patients suggested that corticalterritory infarcts, border zone infarcts and deep small infarcts were 46.4%,56%, and 44.0% respectively, DWI was more sensitive for cortical smallinfarct and centrum semiovale infarcts. MCAOD patients seldom showedlarge infarcts in MCA territory, multiple chain-like infarcts in internalborder zone or centrum semiovale with the size less than 10mm were themost common pattern.Conclusions: Although any infarcts pattern may occur in MCAODpatients, the most common stroke pattern of MCAOD patients is multipleinfarction, which usually involved internal border zone and centrumsemiovale with chain-like or arciform shape distribution, it's pathogenesisis artery-artery emboli. Other 50 percent patients showed deep smallinfarcts or cortical territory infarcts. Single striatocapsular infarction orgiant lacunae were frequently associated with MCA stem stenosis, whichinduced occlusion of the origin of the lenticulostriate artery, were differentfrom the small artery disease in pathogenesis and therapeutic anddiagnostic methods. Total infarcts of MCA cortical territory and centrumsemiovale infarct are associated with severe stenosis or occlusion of MCA.Therefore, we conclude that hemodynamic disturbance is responsible fortotal cortical infarcts and centrum semiovale infarcts. DWI is moresensitive for cortical and subcortical small infarcts than FLAIR MRI, andmore helpful to understand infarct pattern and pathogenesis of MCAODpatients.3. The pathogenesis of subcortical infarcts in patients with MCA occlusivediseaseObjectives: To investigate the pathogenesis of subcortical infarcts inpatients with MCA occlusive disease, because different pathophysiologyrequire different strategy for stroke treatment and prevention.Methods: We prospectively studies 86 acute ischemic stroke withMCAOD by diffusion-weighted magnetic resonance imaging(DWI),among of them, 47 patients were done embolic monitoring again withtranscranial Doppler (TCD) in the distal of stenostic MCA. Acutesubcortical infarcts include internal border zone infarcts and centrumsemiovale infarcts and striatocapsular infarcts and they were categrozied assingle infarct and multiple infarcts according to the number of lesions onDWI. Positive microembolic signal were recorded and the relationshipbetween infarct pattern in DWI and the results of TCD monitoring wereanalyzed.Results: DWI showed that 23 patients(26.7%) had single acute lesionand 63(73.3%) patients had acute multiple infarcts, and the later mainlyinvolved internal border zone(74.4%), which were located in the junctionsbetween the deep penetrating artery and surperior medullary artery of MCA.Twenty-five patients(29.1%) showed multiple centrum semiovale infarcts,which accompanied with cortical small infarcts or IBZ infarcts. TCDmonitoring showed that microembolic signal were detected in 14 patients,among of them, 13 patients were multiple infarcts, account for 40.6% of alldetected patients with multiple infarts, including centrum semiovaleinfarcts(9 cases), IBZ infarcts(8 cases) and cortical small infarcts(6 cases).Microembolic signal were associated with multiple infarcts(P<0.02),centrum semiovale(P<0.001) and cortical small infarcts(P<0.001). Butinternal border zone infarcts and other stroke type were not associated withmicroembli signal.Conclusions: Our study suggests that subcortical infarcts withMCAOD characterized as multiple lesion and combination of artery-arteryembolism and hemodynamic low-flow is the main pathogenesis ofsubcortical multiple infarcts. The clearance and destination of emboli wereaffected by hemodynamic. And microemboli is susceptive to lodge andocclude the most remote artery in hypoperfusion state. The mechanism ofinternal border zone infarct isn't completely the same as that of centrumsemiovale infarct and cortical small infarct, and embolic pathogenesismakes a greater contribution to centrum semiovale and cortical smallinfarctions than internal border zone infarctions in MCAOD patients.Different mechanism require different therapeutics, we should increasedwhole artery pressure and blood volume to increase cerebral blood flow forthe patients with low-flow infarct, prescribe congulation medicine andstatin for the patients with artery-artery embolism to inhibit the thrombosisand steady the plaque.