REVIEW

Stroke: Anatomy of A Catastrophic EventJOHN ZHANG, ADAM LEWIS, DAVID BERNANKE, ALEXANDER ZUBKOV, AND BEN CLOWER

Subarachnoid hemorrhage (SAH) resulting from the rupture of a cerebral aneurysm represents one major cause ofstroke. SAH may be followed by a spontaneous severe contraction of major cerebral arteries, a condition referred to ascerebral vasospasm. Vasospasm may result in brain ischemia or actual tissue death. This constrictive vascular state isdevastating, remains largely untreatable, and is a major cause of morbidity and mortality in SAH patients.Approximately 30,000 Americans are affected by this condition each year. The overall death rates are 25%, andsignificant neurological complications occur in 50% of individuals who survive the initial bleed. This report highlightssome of the important aspects of this vascular disease. Anat. Rec. (New Anat.) 253:58-63, 1998. r 1998 Wiley-Liss, Inc.

KEY WORDS: stroke; subarachnoid hemorrhage; vasospasm

CASEA 48-year-old women was admitted tothe University of Mississippi MedicalCenter after 7 days of a severe head-ache. On admission, she was in poorneurologic condition, unresponsive tovoice and painful stimuli. She hadnonreactive pupils, and corneal andgag reflexes were absent. A computedtomographic (CT) scan of the brainshowed diffuse bleeding into the spaceimmediately surrounding the brain(subarachnoid space); this is subarach-noid hemorrhage (SAH) (Fig 1A). Aventriculostomy was performed imme-diately to remove fluid and reducepressure. Over a few hours her neuro-logical condition improved so that shecould open her eyes and follow simplecommands. Transcranial doppler ultra-sonographic (TCD) measurements ofcerebral vessels showed increased ve-locity of blood in the middle cerebralarteries, indicating cerebral vaso-spasm. Cerebral angiography showedsevere cerebral vasospasm in the inter-

nal carotid arteries, middle cerebralarteries, and anterior cerebral arter-ies. In addition to generalized cerebralvasospasm, an aneurysm of the rightposterior communicating artery andof the left ophthalmic artery was alsoseen (Fig. 1B,C). An infusion of intraar-terial papaverine (to reduce spasms)and ballon angioplasty was performedto reverse the cerebral vasospasm (Fig.1D). Repeat angiography the follow-ing day showed recurrent severe dif-fuse vasospasm of the major arteries.Despite another infusion of papaver-ine, the patient failed to improve. Shedied from rebleeding of the right oph-thalmic aneurysm on the thirteenthday after admission.

INTRODUCTION

OverviewThe above account is common after apatient suffers SAH from a rupturedcerebral aneurysm. While SAH repre-sents one major type of stroke, theother types result from sudden occlu-sion of a vessel (thromboembolic isch-

emia) or from the rupture of a vesselwithin the substance of the brain (in-tracerebral hemorrhage). The mostcommon cause of spontaneous SAH isa ruptured intracranial aneurysm. Sub-arachnoid hemorrhage may also becaused by trauma, vascular malforma-tions, hypertension or coagulation dis-orders.1,2 Aneurysmal SAH is a devas-tating condition. Over the years theepidemiology, clinical presentation, di-agnostic studies, prevention, and treat-ment of SAH have been carefully re-viewed.1–5 Here we will consider theanatomic changes that occur in cere-bral arteries after spontaneous SAHafter briefly reviewing the clinicalpoints related to this type of vascularlesion in the brain.

EpidemiologySpontaneous SAH represents 5–10%of all strokes, and about 30,000 Ameri-cans will suffer an SAH each year.2,4,6

Overall death rates are 25%, and sig-nificant complications occur in 50% ofindividuals who survive SAH. Autopsystudies reveal that about 5% of thepopulation has an unruptured intra-cranial aneurysm.7

Although aneurysms range in sizefrom 2 mm to 5 cm, the average size ofa ruptured aneurysm is approximately7 mm.2,7 Ten percent of all aneurysmsare classified as giant; these have adiameter greater than 2.5 cm. Theincidence of multiple aneurysms (more

The most common causeof spontaneous SAH is a

ruptured intracranialaneurysm.

Associate Professor Zhang, AssistantProfessor Lewis, and Research Associ-ate Zubkov are with the Department ofNeurosurgery at the University of Mis-sissippi Medical Center in Jackson. As-sociate Professor Bernanke and Profes-sor Clower are affiliated with theDepartment of Anatomy at the same in-stitution.

Grant sponsor: American Heart Asso-ciation.

58 THE ANATOMICAL RECORD (NEW ANAT.)

than one in the same patient) rangesfrom 20–35%.2 The risk of ruptureincreases with age, and women aremore commonly affected than men bya ratio of 3 to 2.1,7 Tobacco use, heavyalcohol consumption, and hyperten-sion are risk factors for SAH. Aneu-rysms may occur more frequently inpatients with connective tissue disor-ders such as Marfan’s syndrome orpolycystic kidney disease.1,2

Symptoms and Signs of SAHThe most common symptom of SAH isa sudden, unusually severe headachethat the patient often describes as the‘‘worst headache of my life.’’ Fre-

quently this headache is associatedwith a loss of consciousness, nauseaand vomiting, sensitivity to light (pho-tophobia), and/or pain in the neck.1

Seizures occur in about 25% of pa-tients and usually at the time of hemor-rhage.

Because the symptoms are nonspe-cific and most patients do not havefocal neurologic signs, 25% of the pa-tients are diagnosed as having a mi-graine or tension headache, a viralillness, or sinusitis. However, patientswho suffer SAH usually have an ele-vated blood pressure and neck stiff-ness. When a cranial nerve is para-lyzed (for example, movements of face,

tongue, eyes are affected), when thebody is partially or completely para-lyzed on one side (hemiparesis), orwhen the patient is confused and le-thargic, the diagnosis is made consid-erably easier. A fall at the time ofhemorrhage may prompt a diagnosisof traumatic rather than spontaneousSAH. Young patients with SAH may bediagnosed as being intoxicated fromdrugs or alcohol. An elevated bloodpressure may suggest a diagnosis ofdisease processes related to hyperten-sion.

Death (Mortality) andComplications (Morbidity)It is important to establish a dignosisof SAH since the leading causes ofdeath or disability after this event in-clude the effects of the initial hemor-rhage, rebleeding, and cerebral vaso-spasm.6 Therapy to limit the effect ofthe initial hemorrhage includes reduc-

ing intracranial pressure and relievinghydrocephalus. Most deaths from theinitial hemorrhage occur in the first 48h and result from increased intracra-nial pressure. The highest incidence ofrebleeding occurs in the first 2 weeks,and rebleeding at this point has an80% mortality rate. The annual risk ofrebleeding decreases with time and isabout 2–3% at 6 months.

Cerebral VasospasmSpasm of blood vessels around thebrain (cerebral vasospasm) occurs inapproximately 70% of patients withruptured aneurysms (Fig. 2). The vaso-spasm appears 3–4 days after SAH,peaks at 7–10 days, and resolves over aperiod of 2–4 weeks. The severity ofcerebral vasospasm is directly propor-tional to the quantity of the SAH.Other risk factors for the developmentof cerebral vasospasm and ischemicstroke include age (older patients are

Figure 1. Computed tomographic scan and angiogram of a patient. Computed tomo-graphic scan (A) of the brain with blood on the brain in the subarachnoid space surface (lightarea at arrow); this is a subarachnoid hemorrhage (SAH). Cerebral angiogram (B) of a patientwith a ruptured ophthalmic artery aneurysm. The arrowhead indicates an aneurysm, whilearrows indicate large cerebral vessels under severe vasospasm. Cerebral angiogram (C)showing vasospasm of two large cerebral arteries (arrows). Balloon angioplasty increased thediameter of the internal carotid artery (D, arrowhead) and the proximal part of the middlecerebral artery (arrow).

Tobacco use, heavyalcohol consumption,

and hypertension are riskfactors for SAH.

REVIEW THE ANATOMICAL RECORD (NEW ANAT.) 59

more susceptable), use of tobacco,other brain diseases, and hydrocepha-lus. Symptoms of a localized loss ofblood supply to a specific region of thebrain (cerebral ischemia) occurs inabout 30–40% of patients with SAH.The peak period for death after astroke and cerebral vasospasm is 10days.

Diagnostic StudiesThe most important diagnostic test forSAH is CT.1,2 The CT scan demon-strates blood in the space surroundingthe brain (subarachnoid space) (Fig.1A), and 95% of patients will showblood on the day of the hemorrhage.The location of blood frequently pre-dicts the location of the aneurysm.The CT scan also shows hydrocepha-lus and brain swelling in patients withSAH. Magnetic resonance imaging(MRI) and magnetic resonance angiog-raphy (MRA) are also important imag-ing procedures that serve as a screen-ing for ruptured aneurysms. The MRAcan also identify blood clots in smallaneurysms or clots within giant aneu-rysms.

Cerebral angiography remains the‘‘gold standard’’ for the evaluation ofcerebral aneurysms and cerebral vaso-spasm (Fig. 1B,C). Therapeutic deci-sions are made based on the configura-tion of the aneurysm, on a cerebralangiogram, and on the presence orabsence of cerebral vasospasm. Trans-cranial Doppler ultrasound (the imag-ing of vessels in the brain through theskull) is a screening study used tomonitor cerebral vasospasm. Early de-tection of cerebral vasospasm allowsthe clinician to implement treatmentto reverse arterial narrowing beforepermanent neurologic deficits occur.

TreatmentDirect surgical clipping is the mosteffective method to eliminate an aneu-rysm and prevent rebleeding.5 Surgeryis best performed prior to the onset ofcerebral vasospasm. Operating duringthe period of cerebral vasospasm in-creases the risk of a poor outcome. Inthe past 5 years, detachable platinumcoils have been used to obliterate aneu-rysms. A catheter is placed within thefemoral artery and passed into an ar-tery in the brain and into the aneu-rysm on that artery. A coil is placed

inside the aneurysm and detached,and the sac of the aneurysm is effec-tively occluded. This method is particu-larly effective in treating aneurysmswith a narrow neck and a wide dome.Aneurysms treated in this way have areduced rate of rebleeding.

To prevent the ischemic complica-tions of cerebral vasospasm, treat-ments are initiated to correct and toimprove cerebral blood flow. Lower-ing the intracranial pressure and drain-ing the fluid that surrounds the brain(cerebrospinal fluid [CSF]) improvesthe perfusion of arteries serving thebrain. Before the aneurysm is clipped,the blood pressure is lowered to avoidrebleeding. After surgery, the bloodpressure is raised, the volume of fluidsin the vessles is increased, and othersteps are taken to prevent brain dam-age due to arterial narrowing. Thepatient also receives medication (suchas nimodipine) in an effort to reducethe incidence of cerebral ischemia. Ifsymptoms persist, balloon angioplasty(a mechanical dilation of the vessel)(Fig. 1D) is done, and vascular injec-tions of papaverine (to reduse thespasm of the muscular wall of theartery) are given to reverse the cere-bral vasospasm.

CEREBRAL ARTERY STRUCTUREThe cerebral arteries have three lay-ers: the tunica intima, the tunica me-dia, and the tunica adventitia. Thetunica intima, the innermost layer,consists of a single layer of endothelialcells which line the luminal (inner)surface of the artery, a connective tis-sue layer called the subintima, and a

layer of elastin called the internal elas-tic lamina (IEL). The IEL separatesthe intimal layer from the tunica me-dia of the vessel. The IEL can bedistinguished in stained histologicalsections as a wavy, reddish, and refrac-tile line. The tunica media, or middlelayer, is the thickest layer and is com-posed primarily of smooth muscle.These smooth muscle cells are indi-vidually surrounded by a collagenousmatrix that is produced by the smoothmuscle cells. Larger muscular arterieshave an external elastic lamina sur-rounding the tunica media, but thislayer is not obvious in cerebral arter-ies. The outermost layer of the artery,the tunica adventitia, consists mainlyof a collagenous matrix populated byfibroblasts.8

The endothelium of the tunica in-tima consists of a thin sheet of squa-mous (flattened) cells providing a con-tinuous lining for the internal surfaceof the vessel. The endothelial cellscontain numerous vesicles and distinc-tive rod-shaped granules enmeshed ina dense matrix. Endothelial cells areconnected to each other by occluding(tight) junctions and communicating(gap) junctions. Beneath the endothe-lial cells is the basal lamina (also calledthe basement membrane), consistingof Type IV collagen, proteoglycans,and glycoproteins. This complex, alongwith the tight junctions of the overly-ing epithelium, forms the permeabil-ity barrier between the blood and thesurrounding tissues (the blood-brainbarrier) which regulates passage ofmolecular substances and helps to pro-vide protection against toxins. In cere-bral arteries, as in some other smallarteries in the body, projections of theendothelial cells extend through thebasal lamina, penetrate the subendo-thelial connective tissue, and, via smallholes in the IEL, contact the adjacentsmooth muscle cells of the tunica me-dia. These junctions may allow cell-to-cell communication and transport oflarge molecules taken up by the endo-thelial cells from the circulatingblood.8,9

The smooth muscle of the tunicamedia is usually the predominant com-ponent of the arterial wall. Smoothmuscle cells seem to be circularlyaligned in the vessel wall but actuallyare arranged helically along the lengthof the vessel. The smooth muscle

Figure 2. Schematic illustration of aneurys-mal rupture and cerebral vasospasm (ar-rows). A diagrammatic illustration of an aneu-rysmal rupture (A) shows blood passing intothe subarachnoid space. A diagrammaticrepresentation of vasoconstriction (B, arrowsindicating narrowing of the vessels) of thevessel from which the aneurysm originatesand of vessels in the immediate vicinity thatwould be bathed in blood.

60 THE ANATOMICAL RECORD (NEW ANAT.) REVIEW

makes up a layer of variable thicknesswhich is responsible for the dynamicchanges in luminal diameter of thevessel. Each smooth muscle cell issurrounded by a basal lamina pro-duced by the cell, as well as a substan-tial amount of collagen fibers that aidin their attachment to other smoothmuscle cells. Smooth muscle cells inarteries are somewhat smaller thanthose found in other muscular organssuch as the gut. Large numbers ofsarcolemmal vesicles arranged in lon-gitudinal rows are a prominent fea-ture as well as myofilaments and densebodies.8,10,11

The mechanical integrity of the tu-nica media, and thus the arterial wall,is aided by considerable amounts ofconnective tissue components. Fibro-blasts, the cells common to connectivetissues, are found in the tunica adven-titia, where they produce abundantamounts of collagenous extracellularmatrix. The substance and strength ofthe arterial wall is made up of thefollowing components: elastic fibers inthe IEL and in the intercellular matrixof the tunica media; collagen fibers inthe tunica media and tunica adventitiaas well as in the subendothelial space;and proteoglycan-rich extracellularmatrix throughout all layers. Disor-ders of elastin and collagen metabo-lism are related to aging and severaldisease states, including the formationand rupture of aneurysms.1,4,8

PATHOLOGY OF ANEURYSMFORMATIONIn humans, blood reaches the brainthrough the internal carotid arteriesand the vertebral arteries. The internalcarotid arteries principally supplyparts of the cerebral hemispheres,whereas the vertebral arteries supplythe brainstem and parts of the spinalcord. Anatomically, the major arteriesthat supply blood to the brain anasto-mose with each other to form a vascu-lar circle at the base of the brain calledthe circle of Willis. The large cerebralarteries located in or around the circleare common sites for aneurysm forma-tion. Aneurysms commonly arise atthe bifurcation of these major arteriesand at the origin of their smallerbranches. They seldom occur in themore distal branches of major arteries

in the brain or in smaller vessels withinthe substance of the brain.1,7

Cerebral arteries show only minoranatomical differences from other ar-teries in the body. They are character-ized by a well-developed internal elas-tic lamina, a paucity of elastic fibers inthe tunica media, little adventitial tis-sue, and no external elastic lamina.7

The paucity of elastic fibers in thetunica media may explain why small(berry) aneurysms are found only inthe cerebral circulation. These saccu-lar-like structures occur at branchpoints of vessels in or near the circle ofWillis. Since the tunica media layer isabsent at branch points in many vascu-lar beds throughout the body, a lack ofthis layer does not fully explain thedevelopment of cerebral aneurysms atbranch points. However, the absenceof an external elastic lamina in brainvessels, coupled with the absence ofthe tunica media, may lead to aneu-rysm formation at branch points.2,7

While aneurysms usually result froma weakened arterial wall, their develop-ment may be augmented by abnormalblood flow patterns within an artery.For example, autopsy studies haveshown that the circle of Willis may beincomplete. The lack of a flow throughthe entire extent of the circle may putadditional stress (pressure) on the arte-rial wall and lead to aneurysm forma-tion. As the blood pulsates against aweak vessel wall, the wall begins tobulge. The vessel wall may bulgeequally in all directions (Fig. 3A), or itmay form a sac arising from only oneside of the wall (Fig. 3B). Aneurysmformation usually takes years, makingthe presence of aneurysms in childrenextremely rare. Risk factors for aneu-rysm development include tobacco

use, hypertension, diabetes, and somecollagen disorders.2 There is a small(11%) incidence of familial aneurysmformation, suggesting that hereditaryfactors are involved.

The etiology of cerebral aneurysmsis thought to be either congenital oracquired. The former is based on con-genital defects in the wall, particularlyat bifurcation sites, and the latter fa-vors aneurysms that development overtime.1,2 Congenital defects resulting inweaknesses in the muscular layer ofcerebral arteries are the most com-mon cause of aneurysm formation andthe leading cause of SAH.1 The weak-ened portion of the wall bulges andoffers little resistance to pressurewithin the artery. While not all aneu-rysms rupture, hypertension and/oratherosclerosis, combined with abnor-mal hemodynamic actions, clearly in-crease the probability of such an out-come.

MORPHOLOGIC CHANGESAFTER CEREBRAL VASOSPASMAfter SAH and during vasospasm, cere-bral arteries undergo distinctive histo-logical changes. There is a generalthickening of the arterial wall, al-though the specific details of the tissuechanges responsible for the increasedthickness are not clear. The structuralalterations can be divided into earlychanges, which occur within a fewdays after SAH, or later changes, whichoccur weeks after the original bleed-ing.

Early Changes in Cerebral ArteryStructure After SAHThe tunica adventitia becomes thick-ened in an inflammatory response tothe blood in the CSF surrounding thebrain. Smooth muscle cells in the tu-nica media appear pale, and thenuclear membrane becomes indis-

Figure 3. Schematic illustration of aneurysmsshowing an equal bulging of the arterial wallin all directions (A) or an aneurysm forming asa sac on one side of the arterial wall (B).

The etiology of cerebralaneurysms is thought tobe either congenital or

acquired.

REVIEW THE ANATOMICAL RECORD (NEW ANAT.) 61

tinct. Smooth muscle cells may alsohave dark (pyknotic) nuclei, usuallyindicating cell damage and death. Themore healthy-looking cells of the tu-nica media change shape, appearinground rather than spindle-shaped.

Other cells, such as macrophages, lym-phocytes, and other cells of the im-mune response, have been identifiedin the tunica media and tunica adven-titia.11 The IEL appears very convo-luted due to the reduction in overall

circumference during vasoconstric-tion. Irregularities of thickness, dupli-cations, and even discontinuities areapparent in the IEL. Thickenings ofthe subintimal layer are often but notalways present in early cases. The en-dothelial cells frequently appear swol-len, and some cells are lifted from theunderlying basement membrane(delamininated) by mechanisms thatremain unclear.9 Blood componentsfound in cerebrospinal fluid after SAHhave been implicated in this delamini-nation. The clinical significance of thisdamage to the endothelium is the earlyloss of the integrity of the blood-brainbarrier.2,11

Late Changes in Cerebral ArteryStructure After SAHTwo weeks after the initial bleed, morechanges occur in the artery wall. Thegross thickening of the arterial wall iseasily seen in a light microscope. Con-nective tissue components increasethroughout the vessel wall, and signifi-cant fibrosis is seen in the tunica me-dia and tunica intima (Fig. 4). The IELappears thinner but irregular and dis-continuous. Often the most strikingfeature of the vasospastic cerebral ar-tery is the subendothelial thickeningdue to fibrotic changes in the subin-tima layer, with accumulations of col-lagen fibers, fibroblasts, and immunecells. Damage to endothelial cells isevidenced by a corrugation of thislayer, detachments leaving bare sec-tions of basal lamina and subintimalconnective tissue, crater formation inindividual cells, and adhesions of plate-

Figure 4. Histology of cerebral arteries. Lightmicroscopy (A) of a large cerebral artery af-fected by vasospasm. Note increased thick-ness of the intimal layer (top arrow), corruga-tion of internal elastic lamina (arrowhead),and increased amount of connective tissuein the tunica medica (light areas indicatedby bottom arrow) Gomori trichrome. 315.Scanning electron microscopy (B) of a smallbranch of the internal carotid artery. Noteincreased thickness of the tunica intima(double arrow), the most striking feature ofvasospasm in small arteries. 375. Transmissionelectron microscopy (C) of a large cerebralartery showing degenerative changes in theendothelial layer (arrow). Note edema andvacuolization of endothelial cells (arrow-head). There is also thickening of subendothe-lial layer and accumulation of cells under thebasement membrane (double arrow).

62 THE ANATOMICAL RECORD (NEW ANAT.) REVIEW

lets, red cells, and thrombi on theluminal wall.9,10

The overall description of the cere-bral artery reflecting the changes dueto vasospasm after SAH can be sum-marized as an artery with enlargedoutside diameter but a narrowed lu-men. The thickness of the wall is dueto fibrotic and proliferative changes inthe subintima and the tunica media.Increased width of the tunica media isevident, but, while it might seem thatthis is due to proliferative changes insmooth muscle cells, it has been sug-gested that contraction of the tunicamedia with shortened and overlappedcells during the vasoconstiction couldbe responsible.12

PATHOGENESIS OF CEREBRALVASOSPASMThe unique feature of cerebral vaso-spasm is that it occurs several daysafter the initial SAH.2 The constrictiveresponse develops very slowly, but onceit occurs it is essentially irreversible.There are numerous theories regard-ing the pathogenesis of cerebral vaso-spasm, but none has been proven. Theprime culprit seems to be productsreleased from the blood clot, particu-larly those of erythrocytes. Platelets,fibrin degradation products, and othersmall molecules such as serotonin,catecholamines, thrombin, plasmin,histamine, and prostaglandins mayplay a role. More recently, investiga-tors have focused on the possible con-tribution of endothelin and adeninenucleotides.5 It is likely that oxyhemo-globin and adenine nucleotides re-leased from blood clots and the genera-tion of endothelin in the spastic vesselwall may play a leading role in the

pathophysiology of cerebral vaso-spasm.

It has been accepted that no oneparticular agent or theory can totallyexplain all aspects of this constrictivevascular condition. In reality, cerebralvasospasm following SAH probablyresults from an interrelated, multifac-torial phenomenon involving suchthings as blood and its by-products,the autonomic nervous system, cellmembrane receptors, the immune sys-tem, and a malfunctioning arterialwall. An adequate knowledge of thenormal anatomy, physiology, molecu-lar biology, genetics, and biochemistry

of the arterial wall is necessary to dealwith this complicated disorder. Ge-netic factors predisposing to aneu-rysm formation and altered cerebro-vascular physiology are incompletelydeciphered. Future advancements inthis field will depend on cooperativeefforts of basic scientists and clini-cians.

ACKNOWLEDGMENTSThis work was partially supported by agrant in aid to H.Z. from the AmericanHeart Association. We thank Dr. D.E.Haines for his valuable suggestion andDr. J.C. Lynch for his support in prepar-ing the line drawings. Ms. Mary Ann

Albin and Ms. Kathy Squires preparedthe drafts of this manuscript.

LITERATURE CITED

1 Batjer HH (1994) Intracranial aneurysm.In Rengachary SS, Wilkins RH (eds): ‘‘Prin-ciples of Neurosurgery.’’ Mosby-Wolfe,Times Mirror International Publishers Ltd.,pp 11.1–11.26.2 Weir B (1987) ‘‘Aneurysms Affecting theNervous System.’’ Baltimore: Williams &Wilkins.3 Cook DA (1995) Mechanisms of cerebralvasospasm in subarachnoid hemorrhage.Pharmacol Ther 66:259–284.4 Kassell NF, Sasaki T, Clohan ART, NazarG (1985) Cerebral vasospasm following an-eurysmal subarachnoid hemorrhage. Stroke16:562–572.5 Macdonald RL, Wang X, Zhang J, MartonLS (1997) Molecular changes with sub-arachnoid hemorrhage and vasospasm.Concepts in Neurosurgery 8:278–293.6 Kassell NF, Torner JC, Haley EC, Jane JA,Adams HP, Kongable GL (1990) The inter-national cooperative study on the timing ofaneurysm surgery. Part 1: Overall manage-ment results. J. Neurosurg. 73:18–36.7 Lee RMKW (1995) Morphology of cere-bral arteries. Pharmacol Ther 66:149–173.8 Simionescu N, Simionescu M (1988) Thecardiovascular system. In Weiss L (ed):‘‘Cell and Tissue Biology,’’ 6th ed. Balti-more: Urban & Schwarzenberg, pp 353–400.9 Smith RR, Clower BR, Grotendorst GM,Yabuno N, Cruise JM (1985) Arterial wallchanges in early human vasospasm. Neuro-surgery 16:171–176.10 Findlay JM, Weir BKA, Kanamaru K,Espinosa F (1989) Arterial wall changes incerebral vasospasm. Neurosurgery 25:736–746.11 Hughes JT, Schianchi PM (1978) Cere-bral artery spasm. A histological study atnecropsy of the blood vessels in cases ofsubarachnoid hemorrhage. J Neurosurg 48:515–525.12 Mayberg MR, Okada T, Bark DH (1990)The significance of morphological changesin cerebral arteries after subarachnoid hem-orrhage. J Neurosurg 72:626–633.

The unique feature ofcerebral vasospasm isthat it occurs several

days after the initial SAH.

REVIEW THE ANATOMICAL RECORD (NEW ANAT.) 63