caplan 2000年的经典演讲-后循环缺血

Louis Caplan Lecture—2000 Posterior Circulation Ischemia: Then, Now, and Tomorrow : The Thomas Willis ISSN: 1524-4628 Copyright © 2000 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514 2000, 31:2011-2023Stroke http://stroke.ahajournals.org/content/31/8/2011 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/reprints Reprints: Information about reprints can be found online at journalpermissions@lww.com 410-528-8550. E-mail: Fax:Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters http://stroke.ahajournals.org//subscriptions/ Subscriptions: Information about subscribing to Stroke is online at by guest on August 13, 2011http://stroke.ahajournals.org/Downloaded from Posterior Circulation Ischemia: Then, Now, and Tomorrow The Thomas Willis Lecture—2000 Louis Caplan, MD To know and appreciate where we are now and where weare going in the future, it is essential to know where we have been. We cannot afford to relive and repeat the history of stroke every several decades. Posterior circulation stroke represents a microcosm of stroke in general. In this presen- tation I first review the development of ideas regarding brain and posterior circulation ischemia and its recognition and treatment. I then share some recent data from a large prospective registry of patients with posterior circulation ischemia. Finally, I look ahead to reflect on what I believe should be the future directions for research and for the care of patients with posterior circulation disease. Patients who present to physicians and hospitals with symptoms that suggest posterior circulation ischemia are handled differently from patients who have symptoms that suggest anterior circulation disease in the great majority of medical facilities in the United States and in the world. A patient who has an attack of dizziness with diplopia and ataxic gait usually has a brain image but seldom has vascular or cardiac investigations. A diagnosis of “vertebrobasilar insufficiency” (VBI) is often made, and physicians then debate whether or not to treat with warfarin-type anticoagu- lants, and, if so, for how long and at what intensity. In contrast, a patient who has right-hand weakness and aphasia is usually evaluated and treated quite differently at the very same facilities. Brain imaging, cardiac investigations, nonin- vasive vascular tests of the carotid and intracranial anterior circulation with the use of extracranial and transcranial ultrasound and/or MR angiography (MRA) and CT angiog- raphy, and catheter angiography are often pursued, depending on the local technological capabilities and experience of the treating physicians. An effort is made to identify the etiology and mechanism of the ischemia. Treatment is then chosen among a variety of possibilities (including carotid artery surgery, angioplasty, anticoagulants, and antiplatelet ag- gregants) depending on the nature, location, and severity of the occlusive disease and the mechanism of ischemia. Why should anterior and posterior circulation ischemia be handled so differently? Does this schizophrenic approach make sense? After all, the internal carotid artery and its branches and the vertebral (VA) and basilar arteries (BA) and their branches are just a few inches apart; they are made of the same coats and look the same under the microscope except for size. These vessels carry the same blood under the same blood pressure. The diseases that affect the blood vessels in the 2 circulations are the same. Do stroke mechanisms really differ between the 2 circulations? How did this differing approach originate, and does it continue to make sense today? These are some questions that I will attempt to answer as I review the development of ideas about posterior circulation ischemia and as I report recent data. Development of Ideas Herein I review how knowledge about the posterior circula- tion evolved. To be as concise as possible, I have eclectically selected key individuals and their contributions. I was fortu- nate to have been mentored by some of the individuals who have made key contributions during the second half of the 20th century. Clinicoanatomic Correlations The first important question that physicians asked concerned the anatomy of the brain. What did the brain look like? How did it work? Which areas were responsible for which func- tions? One of the very first important observers was Sir Thomas Willis. Willis (1621–1675) was born soon after the deaths of Shakespeare and Queen Elizabeth. Great Britain was still basking in the artistic and cultural bloom of Elizabethan England. Willis was a very successful practicing physician and an accomplished organizer, teacher, and re- searcher. He performed necropsies on his patients and did extensive anatomic dissections, especially on the brain. His coworkers included the physicists Robert Hooke and Robert Boyle; Richard Lower, an anatomist, physiologist, and clini- cian who administered the first blood transfusion1; and Sir Christopher Wrenn, the renowned architect and artist. Wrenn is responsible for the engraved plates from which the illus- trations in Willis’ The Anatomy of the Brain and Nerves2,3 are derived. Willis became the Sedleian Professor of Natural Philoso- phy at Oxford University. His anatomy text contains detailed description of the brain stem, the cerebellum, and the ventri- The opinions expressed in this paper are not necessarily those of the editors or of the American Heart Association. From the Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Mass. Presented as the Thomas Willis Lecture at the American Heart Association 25th International Stroke Conference, New Orleans, La, February 10, 2000. Correspondence to Louis Caplan, MD, Department of Neurology, Dana 779, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. E-mail lcaplan@caregroup.harvard.edu (Stroke. 2000;31:2011–2023.) © 2000 American Heart Association, Inc. Stroke is available at http://www.strokeaha.org 2011 Special Report by guest on August 13, 2011http://stroke.ahajournals.org/Downloaded from cles, with extensive hypotheses about the functions of these brain parts. He was the first person to use the term neurology. Willis knew and collaborated with other 17th century giants: Sir Isaac Newton; John Locke, physician and philosopher; and William Harvey. After Willis, there was a relative lull in activity concerning brain anatomy and function until the latter years of the 19th century, when physicians, mostly in France, Germany, and the United Kingdom, reported case studies of patients that helped to elucidate the anatomy and functioning of the brain stem. The so-called classic brain stem syndromes, all ep- onymic and named after the original describers of the syndromes, were stimulated by a fascination of the authors with the anatomy and functions of the brain stem.4 We still recognize today these various constellations of findings as the midbrain syndromes of the following: Weber4,5 (ipsilateral third nerve paresis and contralateral hemiparesis); Benedikt4,6–8 (ipsilateral third nerve paresis and contralateral hemiparesis, tremor, and involuntary movements); Claude8–10 (ipsilateral third nerve paresis and contralateral limb ataxia with gait ataxia); the pontine syndromes of Millard- Gubler11,12 (ipsilateral facial palsy and contralateral hemipa- resis) and Foville13 (ipsilateral facial palsy and conjugate gaze paresis with contralateral hemiplegia); the medullary syndromes of Wallenberg14,15 (lateral medullary syndrome) and Babinski-Nageotte16 (lateral medullary syndrome with a contralateral hemiparesis); and the thalamic syndrome of Dejerine-Roussy17 (contralateral hemisensory loss with con- tralateral ataxia and clumsiness and delayed onset of pain). Many of the lesions described in these reports were not vascular in etiology; some were tuberculomas, tumors, and focal infections. Although most reports were single necropsy- based case reports, some had no necropsy confirmation. Wallenberg’s reports were particularly exemplary. He re- ported detailed clinical findings, predicted the location of the medullary lesion, and then later described the necropsy findings.14,15 The next important contributor was Joseph Jules Dejerine (1849–1917). Dejerine was a master clinician and anato- mist.18,19 He was a large man who created an imposing image on ward rounds (Figure 1). Dejerine was associated with the Salpetriere and Bicetre hospitals in Paris, and in 1910 he assumed the Charcot chair. His wife, Augusta Klumpke, was an accomplished clinician and artist.20 She is responsible for the elegant illustrations in Dejerine’s 2 major contributions: his anatomy21 and semiology22 texts. Dejerine and Dejerine- Klumpke drew illustrative cartoons that depicted the symp- toms and signs in patients with various brain stem and cerebral lesions. Figure 2 shows one of the cartoons depicting the anatomy and findings in a patient with a hemimedullary infarct. Dejerine described the findings in patients with different varieties of reading abnormalities and first described the syndrome of alexia without agraphia.23 Charles Foix (1882–1927) was probably the first modern stroke neurologist. Foix was born in Salies-de-Bearn, a small village in southern France.24,25 He spent his entire medical career within the hospital systems of Paris (Hotel Dieu, Necker, Bicetre, Salpetriere). He was a clinician, anatomist, revered teacher, writer, and poet. Within a 3-year period (1924–1927), he and his coworkers published an astonishing array of reports concerning the clinicoanatomic correlation of symptoms and signs with softenings at various sites in the cerebral hemispheres and the brain stem.26 Especially impor- tant in relation to posterior circulation disease were his studies of the thalamic syndromes,27 syndromes related to occlusions of the posterior cerebral arteries,28 and the lateral medullary syndrome.29 Later clinicians clarified the clinical findings in patients with pontine infarction related to basilar artery occlusion30; patients with cerebellar infarction at various loci in the cerebellum31–35; midbrain, thalamic, and occipital and temporal lobe infarction in patients with embolism to the “top-of-the-basilar” artery35,36; and patients with small localized infarcts in the pons, medulla, and thalamus caused by disease of the penetrating artery supply.35,37–46 Vascular Anatomy Concurrent with the interest in how the brain looked and how it worked was an interest in how the different parts of the brain were supplied with blood. Thomas Willis was probably the first to study the circulatory supply of the brain in detail. He wrote the following about the anatomy of the vertebral circulation: as the Carotides carry the tribute of the blood to the brain; so the Vertebrals serve chiefly for watering the cerebellum and the hinder part of the oblong marrow. . . . The Vertebral Artery passes through little holes cut in the extuberances of the Vertebrae till it comes near the base of the skull and is admitted through the Figure 1. Ward rounds at the Salpetriere. Jules Dejerine, with white robe and black hat, is the imposing figure standing on the right. Reprinted with permission from Dejerine J, Gaukler E. Les manifestations fonctionelles des psychoneuroses. Paris, France: Masson et Cie; 1911. 2012 Stroke August 2000 by guest on August 13, 2011http://stroke.ahajournals.org/Downloaded from last hole. . . . Beneith the Cerebellum the Vertebral branches are united.2 Willis is usually remembered as the describer of the vascular composition of the large arteries at the base of the brain, the so-called circle of Willis. He emphasized the capability for collateral circulation if an artery became blocked and the interconnection of blood vessels (Figure 3). A section in his anatomy text is devoted to “for what use the wonderful net is made, and the reason for it.”2 Charles Foix and his colleagues dissected and described in detail the arteries of both the anterior and the posterior circulation. They described the arterial supply of the thala- mus,27,47 the posterior cerebral artery and its branches,28 and the blood supply of the pons48,49 and the medulla oblongata.29 Especially important was the description of the pattern of blood supply of the pons (Figure 4).48,49 The pattern of large median arteries, smaller paramedian arteries, and circumferential arteries is a model for the circulatory supply of the brain stem and also the cerebral hemispheres. Foix also analyzed the clinical findings ex- pected in case of occlusion of the various pontine penetrating and circumferential supply arteries.49 Duret50,51 and Duvernoy52 in France, Stopford53 in En- gland, and Gillilan54 and Stephens and Stilwell55 in the United States were also important contributors to knowledge of the arterial and venous anatomy of the posterior circulation. Vascular Pathology and the Mechanism of Brain Infarction During the first half of the 19th century, the terms encepha- lomalacia, softenings, and ramollissements were in general use. These were all descriptive terms and did not indicate etiology. Not until the observations of Rudolf Virchow (1821–1902) was it established that arterial occlusions and diminished blood flow to brain regions were the cause of softenings and that these lesions were infarctions. Laennec had already used the term infarction for pulmonary apoplectic lesions.56 In 1846, Virchow performed 76 necropsies and Figure 2. Dejerine diagram of the hemimedullary syndrome. The large cartoon above illustrates left facial sensory loss and atrophy of the left side of the tongue, as well as right limb hemiplegia and sensory loss. The small cartoon inserts show left pharyngeal (right insert) and left vocal cord (left insert) paralysis. The anatomic dia- gram below shows the area of infarction on the right as a gray zone. Reprinted with permission from Reference 22. Figure 3. Drawing of the carotid arteries and their communica- tions from Willis’ anatomy. The legend reads, “Shews the ascent of the Caritidick Arteries, and their situation in a horses skull. AA. Either Carotidick Artery ascending toward the Skull. BB. The Trunk of either, having past the Skull, pressed down as it were into a valley. CC. The communications of either by cross Branches. DD. A branch from either Trunk destinated for the Dura Mater. Dddd. Little shoots on either side sent into the pitu- itary Glandula or Kernel. EE. FF. Either Carotidick Artery being divided before it reaches the Brain, and ascending with a dou- ble Trunk.” Reprinted with permission from Reference 3. Figure 4. Foix’s schema of the blood supply of the brain stem. a, Long circumferential artery; b, short circumferential artery; c, larger paramedian artery; d, “protuberance” (pons); e, cerebellar vermis; and f, lateral lobe of the cerebellum. Reprinted with per- mission from Reference 47. Caplan The Thomas Willis Lecture—2000 2013 by guest on August 13, 2011http://stroke.ahajournals.org/Downloaded from found blood clots in 18 peripheral veins and 11 pulmonary arteries.56,57 He concluded that the blood stream allowed transport of venous coagula for distances from their origins. He then described necropsy material in which thrombi orig- inating in the left atria or cardiac valves blocked cerebral, splenic, and renal arteries. In animals, Virchow showed that foreign materials placed into the jugular vein traveled to the lungs and foreign materials placed in arteries also traveled to distant arterial sites.56–58 Virchow showed that thrombi that formed within arteries were often caused by lesions of the arterial wall. Before his work, blockage of arteries was usually attributed to inflammation. Virchow introduced the terms thrombus, thrombosis, embolus, and embolism and deduced the general principles of thrombosis and embolism.56 Virchow’s triad explained localized thrombus formation and consisted of the following: (1) an abnormality of the intima and vascular wall, (2) an abnormality of blood flow, and (3) an abnormality of blood coagulability. Virchow’s patho- logical studies revolutionized thinking about brain infarction, thrombosis, and embolism. The early studies of Charles Foix related strictly to the localization of ramollissements (brain softenings) and their vascular supply and accompanying clinical findings. He and his predecessors had shown little interest in the nature and mechanisms of the vascular occlusive process. Several weeks before his death (Foix died at the age of 45 years, likely of a ruptured appendix), Foix and his colleagues Hillemand and Ley delivered a paper at a meeting of the Medical Society of the Hospitals of Paris concerning a study that they performed on the arteries that led to brain infarcts. Although an abstract of this report was published,59 a full article never appeared. Among 56 brains with infarcts, the artery supplying the infarcts was totally occluded in only 12 and subtotally in 14. In 30 patients the arteries were open. Foix and his colleagues speculated on possible explanations of the arterial patency: (1) arterial occlusion might follow softenings, (2) embolism with distal passage before necropsy, (3) insufficiency (l’insuffisance arterielle), that is, more proximally located circulatory failure, and (4) vasospasm (spasme arterielle). The next important contributor was Raymond Adams, a neuropathologist and clinical neurologist. With Charles Kubik, then director of the neuropathology laboratory at the Massachusetts General Hospital (MGH), Adams, who at the time was director of the neuropathology laboratory at the Mallory Institute of the Boston City Hospital, described the clinical and necropsy findings in 18 patients who at necropsy had occlusion of the basilar artery.30 Eleven occlu- sions were thought to arise in situ, while 7 were considered embolic. Adams and Kubik described the clinical findings and diagrammed in each case the location of the arterial occlusion and the resulting brain stem and cerebellar infarcts (Figure 5). They noted morphological distinctions between thrombosis and embolism, as follows: Thrombosis of the basilar artery could usually be recognized at a glance. The thrombosed portion of the vessel was distended, firm, and rigid and the throm- bus could not be displaced by pressure. . . . In embolism, the embolus was usually lodged in the distal portion of the basilar artery.30 Thrombosis was engrafted on arteriosclerotic lesions, while a displaceable embolus often blocked a normal- appearing artery. Thrombosis was often superimposed on emboli distally and/or proximally.30 Adams later became chairman of the Neurology Department at MGH, where he and his protege Charles Miller Fisher performed many important clinical and pathology studies of various stroke conditions. C. Miller Fisher is the individual probably most responsi- ble for furthering information about stroke and stroke mech- anisms during the 20th century. Fisher, a Canadian by birth, came to the Boston City Hospital and later to MGH to study neuropathology with Raymond Adams. He created the Stroke Service at MGH, the first of its kind in the United States. I was a Stroke Fellow with Dr Fisher in 1969–1970, at which time I also came under the tutelage of Raymond Adams. Fisher’s 1951 report on occlusion of the internal carotid artery was a benchmark in the history of stroke.60 This article emphasized that occlusions commonly developed in the neck engrafted on atherosclerosis and that transient ischemic at- tacks (TIAs) often precede