This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (154)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Cerebrovascular Disease  • Alert me on articles by topic

Louis R. Caplan, MD; Michael Hennerici, MD

Arch Neurol. 1998;55:1475-1482.

Objective  To explore the relationship between hypoperfusion, embolism, and brain infarction.

Design  We studied 4 situations in which brain infarction is related to hypoperfusion: extracranial and intracranial occlusive vascular disease, reduced functional vascular reserve in patients with carotid artery occlusive disease, reduced collateral blood flow in patients given thrombolytic treatment, and cardiac surgery. We reviewed results of emboli monitoring using transcranial Doppler ultrasonography.

Results  Hypoperfusion is strongly linked to brain ischemia and infarction. The evidence includes close correlation of (1) the severity of arterial stenosis with brain infarction; (2) impaired functional blood flow reserve in patients with carotid artery disease and subsequent brain infarction; (3) reduced collateral blood flow with poor prognosis after thrombolysis; and (4) stroke-related neurologic deficits after cardiac surgery to hypoperfusion during surgery. Microembolization is common in patients with severe symptomatic carotid artery stenosis and during and after cardiac surgery.

Conclusions  Hypoperfusion and embolism often coexist and their pathophysiological features are interactive. Arterial lumenal narrowing and endothelial abnormalities stimulate clot formation and subsequent embolization. Reduced perfusion limits the ability of the bloodstream to clear or wash out emboli and microemboli and reduces available blood flow to regions rendered ischemic by emboli that block supply arteries. The brain border zones are a favored destination for microemboli that are not cleared. We posit that impaired washout is an important but neglected concept that intertwines hypoperfusion, embolization, and brain infarction.

From the Department of Neurology, Beth Israel Deaconess Medical Center, Tufts University, Boston, Mass (Dr Caplan), and Heidelberg University, Mannheim, Germany (Dr Hennerici).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

A 70-Year-Old Man With a Transient Ischemic Attack: Review of Internal Carotid Artery Stenosis
Caplan
JAMA 2008;300:81-90.
ABSTRACT | FULL TEXT  

Anterior cerebral artery infarction: Stroke mechanism and clinical-imaging study in 100 patients
Kang and Kim
Neurology 2008;70:2386-2393.
ABSTRACT | FULL TEXT  

An Acute Ischemic Stroke Classification Instrument That Includes CT or MR Angiography: The Boston Acute Stroke Imaging Scale
Torres-Mozqueda et al.
Am. J. Neuroradiol. 2008;29:1111-1117.
ABSTRACT | FULL TEXT  

Cerebral Ischemic Lesions on Diffusion-Weighted Imaging Are Associated With Neurocognitive Decline After Cardiac Surgery
Barber et al.
Stroke 2008;39:1427-1433.
ABSTRACT | FULL TEXT  

Preliminary Findings of External Counterpulsation for Ischemic Stroke Patient With Large Artery Occlusive Disease
Han et al.
Stroke 2008;39:1340-1343.
ABSTRACT | FULL TEXT  

Incidence, Topography, Predictors and Long-Term Survival After Stroke in Patients Undergoing Coronary Artery Bypass Grafting
Filsoufi et al.
Ann. Thorac. Surg. 2008;85:862-870.
ABSTRACT | FULL TEXT  

Endovascular Therapy of Symptomatic Intracranial Stenosis in Patients With Impaired Regional Cerebral Blood Flow or Failure of Medical Therapy
Puetz et al.
Am. J. Neuroradiol. 2008;29:273-280.
ABSTRACT | FULL TEXT  

Brain Perfusion Territory Imaging: Methods and Clinical Applications of Selective Arterial Spin-labeling MR Imaging
van Laar et al.
Radiology 2008;246:354-364.
ABSTRACT | FULL TEXT  

Diffusion-Weighted Imaging in Stroke Attributable to Internal Carotid Artery Dissection: The Significance of Vessel Patency
Bonati et al.
Stroke 2008;39:483-485.
ABSTRACT | FULL TEXT  

Vertebral artery stump syndrome
Nguyen et al.
J. Neurol. Neurosurg. Psychiatry 2008;79:91-92.
ABSTRACT | FULL TEXT  

Cardiac Anesthesia
Savino and Cheung
Card Surg Adult 2008;3:281-314.
FULL TEXT  

Cerebral Border Zones between Distal End Branches of Intracranial Arteries: MR Imaging
Hendrikse et al.
Radiology 2007;0:2461062100.
ABSTRACT | FULL TEXT  

Anterior Cerebral Artery Emboli in Combined Intravenous and Intra-arterial rtPA Treatment of Acute Ischemic Stroke in the IMS I and II Trials
King et al.
Am. J. Neuroradiol. 2007;28:1890-1894.
ABSTRACT | FULL TEXT  

Paradoxical Clustering of Brain Metastases in an Underperfused Cerebral Hemisphere
Yountz et al.
Arch Neurol 2007;64:1659-1660.
ABSTRACT | FULL TEXT  

Changes in Cerebral Perfusion after Revascularization of Symptomatic Carotid Artery Stenosis: CT Measurement
Waaijer et al.
Radiology 2007;245:541-548.
ABSTRACT | FULL TEXT  

Pretreatment Ipsilateral Regional Cortical Blood Flow Influences Vessel Recanalization in Intra-Arterial Thrombolysis for MCA Occlusion
Jovin et al.
Am. J. Neuroradiol. 2007;28:164-167.
ABSTRACT | FULL TEXT  

Borderzone Infarction: Stroke Topography Does Not Easily Equate With Stroke Mechanism
Phan et al.
Stroke 2006;37:2658-2658.
FULL TEXT  

Response to Letter by Phan et al
Yong and Bang
Stroke 2006;37:2659-2659.
FULL TEXT  

Watershed Strokes After Cardiac Surgery: Diagnosis, Etiology, and Outcome
Gottesman et al.
Stroke 2006;37:2306-2311.
ABSTRACT | FULL TEXT  

Stroke Thrombolysis: Slow Progress
Caplan
Circulation 2006;114:187-190.
FULL TEXT  

Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices.
Hogue et al.
Anesth. Analg. 2006;103:21-37.
ABSTRACT | FULL TEXT  

Clinically Silent Cerebral Ischemic Events After Cardiac Surgery: Their Incidence, Regional Vascular Occurrence, and Procedural Dependence
Floyd et al.
Ann. Thorac. Surg. 2006;81:2160-2166.
ABSTRACT | FULL TEXT  

Rate, Predictors, and Consequences of Hemodynamic Depression After Carotid Artery Stenting
Gupta et al.
J Am Coll Cardiol 2006;47:1538-1543.
ABSTRACT | FULL TEXT  

Internal and Cortical Border-Zone Infarction: Clinical and Diffusion-Weighted Imaging Features
Yong et al.
Stroke 2006;37:841-846.
ABSTRACT | FULL TEXT  

Lesion Patterns and Stroke Mechanism in Atherosclerotic Middle Cerebral Artery Disease: Early Diffusion-Weighted Imaging Study
Lee et al.
Stroke 2005;36:2583-2588.
ABSTRACT | FULL TEXT  

Infarcts in the posterior circulation territory in migraine. The population-based MRI CAMERA study
Kruit et al.
Brain 2005;128:2068-2077.
ABSTRACT | FULL TEXT  

Multiparametric MRI and ultrasound findings in patients with internal carotid artery dissection
Lanczik et al.
Neurology 2005;65:469-471.
ABSTRACT | FULL TEXT  

A syndromal analysis of neuropsychological outcome following coronary artery bypass graft surgery
Kneebone et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:1121-1127.
ABSTRACT | FULL TEXT  

Impaired Clearance of Microemboli and Cerebrovascular Symptoms During Carotid Stenting Procedures
Orlandi et al.
Arch Neurol 2005;62:1208-1211.
ABSTRACT | FULL TEXT  

Applied Neuromonitoring and Improving CNS Outcomes
Murkin
SEMIN CARDIOTHORAC VASC ANESTH 2005;9:139-142.
ABSTRACT  

Emergency Carotid Artery Stent Placement in Patients with Acute Ischemic Stroke
Imai et al.
Am. J. Neuroradiol. 2005;26:1249-1258.
ABSTRACT | FULL TEXT  

Applied Neuromonitoring in Cardiac Surgery: Patient Specific Management
Saidi and Murkin
SEMIN CARDIOTHORAC VASC ANESTH 2005;9:17-23.
ABSTRACT  

The Pathophysiology of Watershed Infarction in Internal Carotid Artery Disease: Review of Cerebral Perfusion Studies
Momjian-Mayor and Baron
Stroke 2005;36:567-577.
ABSTRACT | FULL TEXT  

Poststenotic Flow and Intracranial Hemodynamics in Patients with Carotid Stenosis: Transoral Carotid Ultrasonography Study
Kamouchi et al.
Am. J. Neuroradiol. 2005;26:76-81.
ABSTRACT | FULL TEXT  

Perioperative Multimodality Neuromonitoring: An Overview
Murkin
SEMIN CARDIOTHORAC VASC ANESTH 2004;8:167-171.
ABSTRACT  

Isolated middle cerebral artery disease: clinical and neuroradiological features depending on the pathogenesis
Lee et al.
J. Neurol. Neurosurg. Psychiatry 2004;75:727-732.
ABSTRACT | FULL TEXT  

Diffusion-Weighted Magnetic Resonance Imaging in Internal Carotid Artery Dissection
Koch et al.
Arch Neurol 2004;61:510-512.
ABSTRACT | FULL TEXT  

Diffusion-Weighted Magnetic Resonance Imaging and Neurobiochemical Markers After Aortic Valve Replacement: Implications for Future Neuroprotective Trials?
Stolz et al.
Stroke 2004;35:888-892.
ABSTRACT | FULL TEXT  

Mechanism of Ischemic Infarct in Spontaneous Carotid Dissection
Benninger et al.
Stroke 2004;35:482-485.
ABSTRACT | FULL TEXT  

Transcranial Doppler and Near-Infrared Spectroscopy Can Evaluate the Hemodynamic Effect of Carotid Artery Occlusion
Vernieri et al.
Stroke 2004;35:64-70.
ABSTRACT | FULL TEXT  

Assessment of the Patient with Hyperacute Stroke: Imaging and Therapy
Provenzale et al.
Radiology 2003;229:347-359.
ABSTRACT | FULL TEXT  

Subcortical White Matter Infarcts: Comparison of Superficial Perforating Artery and Internal Border-Zone Infarcts Using Diffusion-Weighted Magnetic Resonance Imaging
Lee et al.
Stroke 2003;34:2630-2635.
ABSTRACT | FULL TEXT  

Short-Term Changes in Cerebral Microhemodynamics after Carotid Stenting
Wilkinson et al.
Am. J. Neuroradiol. 2003;24:1501-1507.
ABSTRACT | FULL TEXT  

Comparison of cerebral embolization during off-pump and on-pump coronary artery bypass surgery
Lund et al.
Ann. Thorac. Surg. 2003;76:765-770.
ABSTRACT | FULL TEXT  

Prevalence and Volume of Internal Border Zone Lesions in Patients With Impaired Cerebral Carbon Dioxide Vasomotor Reactivity: A Follow-up Study
Bisschops et al.
Arch Neurol 2003;60:1233-1236.
ABSTRACT | FULL TEXT  

Collateral Circulation
Liebeskind
Stroke 2003;34:2279-2284.
ABSTRACT | FULL TEXT  

Benefits of off-pump bypass on neurologic and clinical morbidity: a prospective randomized trial
Lee et al.
Ann. Thorac. Surg. 2003;76:18-26.
ABSTRACT | FULL TEXT  

Cerebral Microembolism Is Blocked by Tirofiban, a Selective Nonpeptide Platelet Glycoprotein IIb/IIIa Receptor Antagonist
Junghans and Siebler
Circulation 2003;107:2717-2721.
ABSTRACT | FULL TEXT  

Collateral flow and ischemic brain lesions in patients with unilateral carotid artery occlusion
Bisschops et al.
Neurology 2003;60:1435-1441.
ABSTRACT | FULL TEXT  

Assessment of the Collateral Function of the Circle of Willis: Three-Dimensional Time-of-Flight MR Angiography Compared with Transcranial Color-Coded Duplex Sonography
Hoksbergen et al.
Am. J. Neuroradiol. 2003;24:456-462.
ABSTRACT | FULL TEXT  

Association Between Impaired Carbon Dioxide Reactivity and Ischemic Lesions in Arterial Border Zone Territories in Patients With Unilateral Internal Carotid Artery Occlusion
Bisschops et al.
Arch Neurol 2003;60:229-233.
ABSTRACT | FULL TEXT  

Patterns of Perfusion-Weighted Imaging in Patients With Carotid Artery Occlusive Disease
Chaves et al.
Arch Neurol 2003;60:237-242.
ABSTRACT | FULL TEXT  

Thromboembolic Events Associated with Guglielmi Detachable Coil Embolization of Asymptomatic Cerebral Aneurysms: Evaluation of 66 Consecutive Cases with Use of Diffusion-Weighted MR Imaging
Soeda et al.
Am. J. Neuroradiol. 2003;24:127-132.
ABSTRACT | FULL TEXT  

Cardiac Anesthesia
Savino et al.
Card Surg Adult 2003;2:249-281.
FULL TEXT  

Is there any impact of the shape of aortic end-hole cannula on stroke occurrence? Clinical evaluation of straight and bent-tip aortic cannulae
Albert et al.
Perfusion 2002;17:451-456.
ABSTRACT  

Progressive Stroke, Lacunae, and Systemic Blood Pressure
Bergui et al.
Stroke 2002;33:2735-2736.
FULL TEXT  

Lesion Patterns and Mechanism of Ischemia in Internal Carotid Artery Disease: A Diffusion-Weighted Imaging Study
Kang et al.
Arch Neurol 2002;59:1577-1582.
ABSTRACT | FULL TEXT  

Hemodynamic Modifications in Patients with Symptomatic Unilateral Stenosis of the Internal Carotid Artery: Evaluation with MR Imaging Perfusion Sequences
Bozzao et al.
Am. J. Neuroradiol. 2002;23:1342-1345.
ABSTRACT | FULL TEXT  

Encephalopathy and Stroke After Coronary Artery Bypass Grafting: Incidence, Consequences, and Prediction
McKhann et al.
Arch Neurol 2002;59:1422-1428.
ABSTRACT | FULL TEXT  

Cardiac Surgery and Magnetic Resonance Imaging of the Brain
Wityk and Restrepo
Arch Neurol 2002;59:1074-1076.
FULL TEXT  

Brain Damage After Coronary Artery Bypass Grafting
Bendszus et al.
Arch Neurol 2002;59:1090-1095.
ABSTRACT | FULL TEXT  

Worsening in Ischemic Stroke Patients: Is it Time for a New Strategy?
Caplan
Stroke 2002;33:1443-1445.
FULL TEXT  

Risk of Stroke, Transient Ischemic Attack, and Vessel Occlusion Before Endarterectomy in Patients With Symptomatic Severe Carotid Stenosis
Blaser et al.
Stroke 2002;33:1057-1062.
ABSTRACT | FULL TEXT  

Hand weakness from a precentral gyrus infarct with intermittent hypotension
De Marinis et al.
Neurology 2002;58:510-510.
FULL TEXT  

Report of the Substudy Assessing the Impact of Neurocognitive Function on Quality of Life 5 Years After Cardiac Surgery Editorial Comment
Newman et al.
Stroke 2001;32:2874-2881.
ABSTRACT | FULL TEXT  

Characteristics of Cerebral Microembolism During Carotid Stenting and Angioplasty Alone
Orlandi et al.
Arch Neurol 2001;58:1410-1413.
ABSTRACT | FULL TEXT  

Long-Term Prognosis of Medically Treated Patients With Internal Carotid or Middle Cerebral Artery Occlusion: Can Acetazolamide Test Predict It? Editorial Comment: Can Acetazolamide Test Predict It?
Kuroda et al.
Stroke 2001;32:2110-2116.
ABSTRACT | FULL TEXT  

Effect of Collateral Blood Flow and Cerebral Vasomotor Reactivity on the Outcome of Carotid Artery Occlusion
Vernieri et al.
Stroke 2001;32:1552-1558.
ABSTRACT | FULL TEXT  

Hand weakness from a precentral gyrus infarct with intermittent hypotension
Altieri et al.
Neurology 2001;56:1748-1748.
FULL TEXT  

Acute Stroke Patterns in Patients With Internal Carotid Artery Disease : A Diffusion-Weighted Magnetic Resonance Imaging Study
Szabo et al.
Stroke 2001;32:1323-1329.
ABSTRACT | FULL TEXT  

Diffusion- and Perfusion-Weighted Brain Magnetic Resonance Imaging in Patients With Neurologic Complications After Cardiac Surgery
Wityk et al.
Arch Neurol 2001;58:571-576.
ABSTRACT | FULL TEXT  

Cerebrovascular Reactivity and Subcortical Infarctions
Cupini et al.
Arch Neurol 2001;58:577-581.
ABSTRACT | FULL TEXT  

Cognitive Changes 5 Years After Coronary Artery Bypass Grafting: Is There Evidence of Late Decline?
Selnes et al.
Arch Neurol 2001;58:598-604.
ABSTRACT | FULL TEXT  

Stroke With Internal Carotid Artery Stenosis
Tsiskaridze et al.
Arch Neurol 2001;58:605-609.
ABSTRACT | FULL TEXT  

Risk stratification and carotid surgery: new technology but old trials
Bamford
Brain 2001;124:455-456.
FULL TEXT  

Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion
Markus and Cullinane
Brain 2001;124:457-467.
ABSTRACT | FULL TEXT  

Coronary-Artery Bypass Surgery and the Brain
Selnes and McKhann
NEJM 2001;344:451-452.
FULL TEXT  

Do transient ischemic attacks have a neuroprotective effect?
Caplan and Bogousslavsky
Neurology 2000;55:1596-1596.
FULL TEXT  

Atherothrombotic Middle Cerebral Artery Territory Infarction : Topographic Diversity With Common Occurrence of Concomitant Small Cortical and Subcortical Infarcts
Min et al.
Stroke 2000;31:2055-2061.
ABSTRACT | FULL TEXT  

Comparison of Microembolism Detected by Transcranial Doppler and Neuropsychological Sequelae of Carotid Surgery and Percutaneous Transluminal Angioplasty
Crawley et al.
Stroke 2000;31:1329-1334.
ABSTRACT | FULL TEXT  

Diffusion- and Perfusion-Weighted MRI Patterns in Borderzone Infarcts
Chaves et al.
Stroke 2000;31:1090-1096.
ABSTRACT | FULL TEXT  

Low Risk of Ischemic Stroke in Patients With Reduced Internal Carotid Artery Lumen Diameter Distal to Severe Symptomatic Carotid Stenosis : Cerebral Protection Due to Low Poststenotic Flow?
Rothwell and Warlow
Stroke 2000;31:622-630.
ABSTRACT | FULL TEXT  

Brain embolism is a dynamic process with variable characteristics
Babikian and Caplan
Neurology 2000;54:797-801.
FULL TEXT  

Angiographically Defined Collateral Circulation and Risk of Stroke in Patients With Severe Carotid Artery Stenosis
Henderson et al.
Stroke 2000;31:128-132.
ABSTRACT | FULL TEXT  

Cerebrovascular Reactivity in Internal Carotid Artery Occlusion • Response
Cheung et al.
Stroke 1999;30 :2759-2768.
FULL TEXT  

Mechanisms and clinical features of posterior border-zone infarcts
Belden et al.
Neurology 1999;53:1312-1312.
ABSTRACT | FULL TEXT  

Treatment of Posterior Circulation Ischemia With Extracranial Percutaneous Balloon Angioplasty and Stent Placement
Malek et al.
Stroke 1999;30:2073-2085.
ABSTRACT | FULL TEXT