CerebrovascularDiseasesOutlineIntroductionTransientIschemicAttacks(TIA)IschemicstrokeIntracerebralHemorrhageSubarachnoidHemorrhageIntroductionl lDefinitionDefinitionl lagroupofbraindysfunctionsrelatedtodiseaseoftheagroupofbraindysfunctionsrelatedtodiseaseofthebloodvesselssupplyingthebrainbloodvesselssupplyingthebrainl lStroke:cerebrovascularaccidentStroke:cerebrovascularaccidentl lsuddenlossofbloodcirculationtoanareaofthebrain,suddenlossofbloodcirculationtoanareaofthebrain,withcorrespondinglossofneurologicfunction.withcorrespondinglossofneurologicfunction.l lAsif“struckbythehandofGod”Asif“struckbythehandofGod”EpidemiologyThirdleadingcauseofdeathApproximately2millionnewstrokeseachyearinchinaAssociatedwithriskfactors(seebelow)Blood supply of the Braininternalcarotidarteryvetebral-basilararterytheyareinterconnectedbyanarterialcircle(ofWillis)INTERNALCAROTIDARTERYINTERNALCAROTIDARTERYEnters cranium via the carotid canal of the temporal boneSupplies dura, hypophysis, tympanic cavity and trigeminal gangliaProvide direct branches to the optic nerve, optic chiasm, hypothalamus and genu of internal capsulTerminalbranchesaretheanteriorandmiddlecerebralarteriesAnteriorcerebralartery(ACA)AnteriorcerebralarteryCortical branches supply all the medial surface of the cerebral cortex (basal ganglia, corpus callosum) as far back as the parieto-occipital sulcus.KeyfunctionalareasPrimarymotorcortexforlegandfootMotorplanninginmedialfrontallobeMiddleandanteriorcorpuscallosumMiddlecerebralarteryMiddlecerebralartery(MCA)Largest branch, Runs in the lateral sulcusDivides into superior and inferior branchSuperior MCA lateral and inferior frontal, anterior part of parietal Inferior MCA lateral temporal, posterior parietal, lateral occipital.Central perforating branches supply the lentiform and the caudate nuclei and the internal capsuleDeep branches of MCAKeyfunctionalareasofMCAPrimarymotorcortexforface,arm,legPrimarysensorycortexforface,arm,legBrocaslanguagearea(superiorMCA)Wernickesarea(inferiorMCA)Perceptionofownbody,outsideworldandabilitytoexpressemotionsAreaofsupplyofcerebralarteriesVERTEBROBASILARSYSTEMEnter the cranial cavity through the foramen magnum.Just inferior to the pons, fuse to form the basilar artery. Keyfunctionalareas1/3 of posterior braincerebellumSpinalcordtractspyramidalandspinothalamicCranialnerves3-12VERTEBROBASILAR SYSTEMVertebralarterybranchesThemeningealbranchesTheposteriorspinalarteryTheanteriorspinalarteryPosteriorinferiorcerebellarartery(PICA)SmallmedullaryarteriesBASILARARTERYBRANCHESPontinearteriesLabyrinthineartery(Suppliestheinternalear)Anteriorinferiorcerebellarartery(AICA)Superiorcerebellarartery(SCA)AnteriorandposteriorspinalarteryPosteriorcerebralartery(PCA)Posteriorcerebralartery(PCA)Blood supply for midbrain, half thalamus, geniculate bodiesoccipital lobe, visual cortex, inferior temporal lobe, including the hippocampusKeyfunctionalareasPrimaryvisualcortex3rdnerveinmidbrainSensorycontroltemperature,pain,sleepCIRCLE OF WILLIS-Bridges ICA and vertibrobasilar arteryCIRCLEOFWILLISFormedbyanastomosisbetweentwointernalcarotidandtwovertebralarteriesThecontributingarteriesareTheanteriorcommunicatingTheanteriorcerebralTheinternalcarotidTheposteriorcommunicatingTheposteriorcerebralThebasilarCerebralbloodflow(CBF)The brain accounts for 2%3% of body weight but utilizes 20%25% of glucose and energy.RegulationofCBFBloodpressure: CBF is automatically regulated when mean arterial pressure (MAP) is between 60-160mmHg (Bayliss effect). Autonomic regulation will not be effective when MAP is below 60mmHg or above 160mmHg (hypertension).Chemicals:O2, CO2 and pH in blood and CSF.Common forms of CVDTIAIschemia（缺血性,8590%）Thrombosis（脑血栓形成）Embolism（脑栓塞） Hemorrhage（出血性,1015%）Intracranial hemorrhage（脑出血） Subarachnoid hemorrhage （蛛网膜下腔出血）RiskfactorsofCVDNon-modifiableriskfactorsAge, Sex , Race, GeneticsModifiable:TIAsHigh blood pressureAtrial fibrillationDiabetesCholesterolOthers: smoking, alcohol, drugs (contraceptive, cocaine, amphetamines), lack of physical activities, obesityPrimary preventionTreatment of risk factors in individuals with no previous history of strokeHypertension: blood pressure to 140/90mmHgAtrial fibrillation: 1/6 of stroke in patients 60 years oldWarfarin +statins(lipid reduction)DiabetesSecondary preventionRisk factor treatment for those who have experienced a strokeBloodpressurelowering:Recommended even for normal blood pressure without stenosisCholesterolloweringLow dose of statins is suggested even for normal cholesterol levelAntiplateletagents aspirin + dipyridamole (双嘧达莫) is better than aspirin aloneClopidogrel: aspirin allergy, or with coronary artery diseaseAnticoagulants:Atrial fibrillation, or TIACarotidintervention:Stenosisof50%:Endarterectomy(proven beneficial for symptomatic, applied within 2 weeks), stenting (angioplasty, 支架成形术, recommended in younger patients of 70 years old). Aneurysms: clipping or coilingSupposed to know in this sectionRisk factors Concepts of primary and secondary prevention of CVDOutlineIntroductionTransientIschemicAttacks(TIA)IschemicstrokeIntracerebralHemorrhageSubarachnoidHemorrhageTransientIschemicAttacks(TIAs)Are episodes of stroke symptoms that only last briefly, with average duration of 12min. Without evidence of infarction50% of TIA recovered within the first hour, 90% recovered within 4 hours. Infarcts do occur in 15 to 40% of TIAs even though neurologic signs and symptoms are absentUrgent risk stratification is requiredCausesandpathophysioloyCauses are similar to all strokePathophysiologyBlood flow dynamics: Atherosclerosis or srenosis + blood pressure fluctuation, or with high coagulative state, Micro-emboli: Atherosclerosis, arterial or vetricular sourcesOthers: Arteritis, arterial steal syndrome (ASS) Clinical presentationsAge: 5070 years oldWith risk factors: hypertension, heart disease, diabetes, abnormal blood lipidAbrupt onsetBrief neurologic deficitsInternal carotid systemVertibro-basal systemInternal carotid TIAsCommon features: contralateral hemiplegia, sensory loss or numbnessCharacteristic presentations: transient monocular blindness(ophthalmic artiery), with contralateral hemiplegia or sensory disturbanceHoners sign (hypothalamus) with contralateral hemiplegiaAphasia (MCA occlusion)Vertibral-basal TIAsCommonfeatures:Vertigo, usually without tinnitus (耳鸣); nausea, vomiting CharacteristicfeaturesDrop attack: brain stemTransient global amnesia: temporal lobe, the hippocampusPossiblesymptoms:Diplopia (复视), nystagmus, dysarthria(构音障碍), dysphgia(吞咽困难),ataxia, disturbance of consciousnessCrossed sensory disturbance: Wallenberg syndrome Crossed paralysis: cranial nerves (brain stem syndromes), will be discussed in detail in next sectionDiagnostic testsRisk factors:Blood pressure, serum lipid and sugar, coagulation (ESR, Erythrocyte sedimentation rate; Thrombin time),artery diseases(atherosclerosis, arthritis), heart disease (atrial fibrillation, patent foramen ovale),TCD (transcranial Dopplar):Large artery blood flow dynamicsArterial stenosis: MRA, CTA, sometimes DSADiagnosisHeavily relies on historyAged peopleTransient signs or symptomsInternal carotid or vertibral-vasal systemlast for min and are recovered in 24 hrsImage study fails to show any lesionsDifferential diagnosisEpilepsy: symptoms last for seconds(5min), stereotyped, loss of consciousness (events can not be recalled), EEG abnormalityMeniere Disease: vertigo/nausea several hrs, with hearing impairment, vestibular dysfunctionMigraine: vertigo sometimes, younger in age (60 years old; duration 10minSymptoms: unilateral motor weakness, speech disturbanceHypertension 140/95mmHgDiabetes Treatment:Hospitalization suggestedAspirin or aspirin + clopidagrel for 2 weeksBlood pressure controlLowering blood sugarDrug treatment for TIAsAntipletlets: Aspirin 50300mg qd.Or aspirin 100mg qd + dipyridamole 2550mg tidOr aspirin 100mg qd + clopidagrel 75mg qd (in acute phase 5070%)Endarterectomy or angioplastyHeartdiseasesHypertensionDiabetesHyperlipidaemiastatinsImportant notes in TIAsDiagnosisofTIAsAgedpeople brief presentation (minutes), recovered within 24hrsNo positive image findingsDifferentialdiagnosisofTIAsTreatment principlesIdentify high risk TIAsDrug choiceUnderlying pathology controlOutlineIntroductionTransientIschemicAttacks(TIA)Ischemicstroke(cerebralinfarction)IntracerebralHemorrhageSubarachnoidHemorrhageCerebral infarction(cerebral ischemic stroke)Major forms of ischemic strokeAtherosclerotic thrombotic cerebral infarctionCerebral embolismLacunar infarction (small-vessel stroke)Border zone infarction (cerebral watershed infarction)They share common pathophysiology and therefore the treatment is similar.EtiologyCommon:Thrombus: Atherosclerosis, dehydrationEmbolus: artery-to-artery, cardioembolic, valvular lesions, patent foremen ovaleLesscommon:Hypercoagulable disorders: sickle cell anemia, SLE, homocysteinemia, oral contraceptivesVenous sinus thrombosisVasculitisVasospasm after subarachnoin hemorrhageDrugs:coccaine, amphatamine,Moyomoya diseaseCBF in ischemiaNormal CBF is approximately 5060 ml/100 g /minPermanent ischemia 17 - 18 ml/100g/min histological changes2 hours ischemia 12 ml/100g/min histological changesReduction of CBF of less than 10 ml/100 g/min results in irreversible neuronal injuryIschemic cascadeLack of oxygen supply to ischemic neuronesATP depletionMembrane ions system stops functioningDepolarisation of neuroneInflux of calciumRelease of neurotransmitters, including glutamate, activation of N-metyl -D- aspartate and other excitatory receptorsat the membrane of neuronesFurther depolarisation of cellsFurther calcium influxCarrol and Chataway,2006Energy failure / depolarisationTransmitter releaseand receptor activation Ca2+Lipolysis (DAG PKC) ProteinphosphorylationProteolysisDisaggregationof microtubuli(FFAs.LPLs)EnzymeconversionBreakdown ofcytoskeletonDamage to membranestructure and functionDysfunction ofreceptors andion channelsFree radicalformationInhibition of axonaltransportCosequences of brain ischemiaIschemic penumbraRing-like area around ischemic centerBlood flow range between the thresholds of transmitters release and cell membranes failureFunctional activity of the neurons is suppressed although structural integrity of the cell is still preserved - neurons are injured but still viableIt provides a rational basis for functional improvements in injured brain tissue occurring long after the onset of stroke MRI of ischemic penumbraDWI/PWI mismatch is increasingly being used to identify patients who are most likely to benefit from new interventions in acute ischaemic strokeCell death and tissue edemaTwo types of cell deathNecrosis: core of infarctApoptosis: may exists in penumbraBrain edema: leading cause of death especially in the first weekMixture of cytotoxic and vasogenic edemaCytotoxic occurs early due to cell energy failure Vasogenic edema occurs latter due to disrupted blood-brain barrierTheconceptofdiaschisis(失联络)Remotedisturbancesofbraincellsduetothesuppressionofneuronsconnectedtotheinjured(ischemic)regionTheremotefocusofbrainsufferakindofshockwhendeprivedfromafferentinputcommingfromischemicfocusDisturbedneurotransmittermetabolismAppearswithin30minaftertheonsetofischemia;reversesafterafewmonthAlsoseeninspinalshockafteracutemyelitisAtherosclerotic thrombotic cerebral infarctionAtherosclerotic thrombotic cerebral infarctionTypes: complete stroke develops within 6 hrs, progressive stroke develops in 6hrs to several daysMiddle to old ageRisk factorsNeurologic defects: hemiplegia, hemianesthesia, aphasia, ataxia. Sometimes vomiting and coma, and , death.Stroke syndromesInternalcarotidarteryMCA,ACAMotor,sensoryandadvancedbrainfunctionVetebrobasilararteryBrainstem,cerebellum,partofhypothalamus,thalamusCranialnerve,cerebellardysfunctionwithcrossedcharacteristicsACA occlusionUsually without neurologic deficitCollaterals from MCA,PCA, or anteriaior communicating arteryParalysis and sensory loss of opposite foot and legUrinary incontinence (paracentral lobule)Contralateral gasp and sucking reflexAbbulia (akinetic mutism), slownessMCA occlusionComplete block: 3 HEMIs: contralateral hemiplegia, hemianesthesia, homonymous hemianopia Gaze preferance to ipsilateral sideAdvanced brain functionAphaia, anosognosia (病觉缺失), constructional apraxia (结构性失用)Vertibral arteries occlusionWallenberg Syn.(lateral medullary syn.)VIII, IX, X cranial nerve: Vertigo, hoarseness, dysarthria, disphagia,Crossed surface sensory loss: ipsilateral face and contrlateral trunk and limbHorners sign (ipsilateral) Ataxia (ipsilateral)Cerebellar infarctionGait unsteadiness,nausea, vomitting, with headache, neck stiffnessEdema can lead to sudden respiratory arrestBasilar artery occlusionThree groups: paramedian (7-10 branches), short circumferential (5-7) and bilateral long circumferential (SCA and AICA)Affects corticospinal and corticobulbar tracts, ascending sensory tracts and cranial nerve nuclei (sensory + motor+ cranial nerves+cerebellum)Complete block usually causes bilateral signsCommon syndromes: basilar artery occlusionMedial inferior pontine syn.(Millard-Gubler Syn.)Ipsilateral facial and abdunct nerve palsyContrlateral hemiparalysisLock-in syn (bilateral pontine infarction)Preserved consciousnessQuapledia and lower cranial nerve signsTop of the basilar syn(TOBS, SCA+PCA)Rostral brain stem: dysfunctional eye movement and pupil(anisocoria,瞳孔不等), disturbance of consciousness, hypersomnia (嗜睡)PCA: memory loss, homonymous hemianopia Hallucination of cerebral peduncle: animated, vivid charateristicsTOBSPCA occlusionCortical branches: contralateral homonymous hemianopia with macula sparing , acute disturbance of memoryPenetrating branches:3rd nerve palsy with contralateral hemiplegia (Weber syndrome), or contralateral ataxia or dyskinesia(Benedikt Syndrome, red nucleus)Thalamic syndrome: contralateral hemisensory loss or burning painImaging studiesCTuseful for identifying ischemia from hemorrhagesensitive to ischemia in brain hemisphere after 24hrsMRICan find small and posterior fossa ischemiaSensitive in several min, but time consumingAngiographyCTA, DSA and MRAHelpful in finding vesculopathiesExamples of CT and MRI (MCA occlusion)a Magnetic resonance angiography, b diffusion-weighted imaging and c perfusion-weighted imaging performed in a patient 2.5 hours after onset of aphasia and right hemiparesis. Occlusion of the left middle cerebral artery trunk (arrow) is seen, with a small diffusion abnormality and a large perfusion abnormality indicative of a large ischemic penumbra (tissue potentially salvageable with thrombolysis).DiagnosisMiddle to old ageRisk factors including previous TIAsSymptoms peak within min to several daysNeurologic deficits correspond to occluded brain areasPositive image findingsDifferential diagnosisThrombotic vs. embolicAge, heart disease, TIAs, onsetIschemic vs. hemorrhagicAge, TIAs, background activity, symptom onset, sings of intracranial hypertension, imaging studySubdural/epidural hematomaHistory of head injury, sings of intracranial hypertension, CT findingSpace occupying lesionsBroken tumor or abscessPrinciples of treatment General management: very importantManagement of brain edemaTargeting on thrombosisThrombolysis, fibrinolytics, anticoagulants, antipltelets (Avoid combined use of these drugs)NeuroprotectionSurgeryRehabilitation General managementAirwayHypertension(200/110mmHg) Blood sugar HyperthemiaUpper gastrointestinal bleedingFluid and electrolyte imbalanceHeart diseaseEpilepsyBrainedemaElevation of the head end of the bed to a 2030 degree angle to improve venous drainage.Hypoxia, hypercapnia, hyperthermia, hyperglycemia, and antihypertensive drugs, particularly those that can cause cerebral vasodilatation, should be avoided.Osmotherapy (manitol, glycerol fructose, corticosteroids). Surgical: decompressive surgery, ventricular drainage.Thrombolysis IndicationsTime window: 4.5 hrs for rt-PA, 6hrs for urokinase(UK)No known intracranial hemorrhageContraindicationsBleeding tendency (history of bleeding, anticoagulants, low plasma platelets), recent (3months) cerebral or cardiac infarction,Special conditions: Pregnant, severe systemic diseases, hypertension, hypoglycemiaUsage of thrombolysisrt-Pa: 0.9mg/kg (maximum 90mg)/ iv. gtt (in 100ml NS)Urokinase(UK)11.5 million IU /iv. Gtt (in 100ml NS)Anticoagulants Not recommended for routine useIndicationsInfarction due to cardiac diseasesIschemia with protein C, S deficiency, dissecting aneurysm and arterial stenosisCarefully monitor IRN (international normalized ratio,65 years, severe stroke, hyperglycemia, and signs of mass effect on pre-treatment imagingCareful selection of thrombolysisCerebral embolismCerebral embolismCardioembolicAtrial fibrillation, myocardial infarction, dilated cardiomyopathy,Valvular lesions: mitral stenosis, mechanical valve, bacterial endocarditisRight-to left shunt: patent foremen ovale (venous clot, fat, bacteria, air, tumor)Artery-to-artery embolicCarotid bifurcation atherosclerosisIntracranial atherosclerosisIn younger patients, dissection of arteriesClinical features and treatmentClinical featuresNeurologic deficits are similar with regard to thrombosisYounger in age, abrupt symptom onset (within sec to min), with primary diseases (most heart disease)TreatmentSimilar to thrombosisAnticoagulants for those with atrial fibrillationLacunar infarction(Small-vessel stroke)Lacunar infarction“lacunes”: Latin for “lake” of fluid noted at autopsyOcclusions of a small cerebral artery(30300um)Penetrating arteries supplying white matter, brain stem or cerebellumResults from atherosclerosis or vessel wall thickeningOccurs in patients with hypertensionRanges in size from 3mm to 2cmAccounts for 20% of all strokesClinical manifestationsPure motor hemiparesis (not complete paralysis)Internal capsule or Base of pons Dysarthria-clumsy hand (arm)Base of pons or genu of the internal capsulePure sensory stroke: hemianesthesiaThalamasAtaxic hemiparesisThe base of ponsCT or MRIWhat should be remembered-for ischemic stroke Diagnosis of cerebral infarctionPrinciples of treatment of cerebral infarctionClinical features of lacunar infarctionThankyouAnyquestions?