mecanismo vascular en tvm

NTENSIVE studies of the pathophysiology of spinalcord injury have provided evidence that the primarymechanical trauma is followed by secondary injury

mechanisms that contribute to the necrotizing process andthat vascular injuries play a key role in both primary andsecondary damage.26,3840 For example, experimental stud-ies have reported significant posttraumatic ischemia at theinjured segment and adjacent areas after severe spinalcord injury.9,10,13,32,33 Using microangiographic techniques,regions of severe ischemia were demonstrated in the trau-matized spinal cord in rats,20,21,34,45 cats,1,5,7,31 rabbits,8,27,44and monkeys.11 The pathophysiology of vascular mecha-nisms of secondary neural injury was the topic of a recentreview.37

In the present study, we investigated the vascular sys-tem in three uninjured human cervical spinal cords usingsilicone rubber microangiography. This technique allowsthree-dimensional analysis of the intramedullary vesselsafter the spinal cord is made transparent with an alco-holmethylsalicylate technique.21 The present study is thefirst to use this technique to visualize the vascular systemin the human spinal cord. It was believed that this tech-

nique would provide useful information for interpretingvascular damage in acute spinal cord injury, especially thephenomena of secondary injury and remote infarction. Inaddition, we analyzed histological findings in nine trau-matized human spinal cords obtained at autopsy. The pur-pose of these studies was to determine the role of vascularinjuries in the pathophysiology of human spinal cordinjury.

Materials and MethodsSilicone Rubber Angiography in the Uninjured HumanSpinal Cord

Uninjured human spinal cords were removed at the cervical levelin three cadavers during autopsy to examine the normal vascularsystem using the silicone rubber microangiographic technique.These three individuals, aged 62 to 77 years old, had had no spinalcord lesions and died of cerebrovascular accidents or pneumonia.The interval from death to autopsy ranged from 18 to 66 hours.Before removing the spinal cord, the left vertebral artery was can-nulated at its origin at the subclavian artery and was infused with800 to 1000 ml saline. The spinal cord was then removed from C-2

J. Neurosurg. / Volume 86 / March, 1997

J Neurosurg 86:483492, 1997

Vascular mechanisms in the pathophysiology of humanspinal cord injuryCHARLES H. TATOR, M.D., PH.D., F.R.C.S.(C), AND IZUMI KOYANAGI, M.D.Canadian Paraplegic Association Spinal Cord Injury Research Laboratory, Division of Neurosurgeryand Playfair Neuroscience Unit, The Toronto Hospital, Western Division, and the University ofToronto, Toronto, Ontario, Canada

U Vascular injury plays an important role in the primary and secondary injury mechanisms that cause damage to theacutely traumatized spinal cord. To understand the pathophysiology of human spinal cord injury, the authors investi-gated the vascular system in three uninjured human spinal cords using silicone rubber microangiography and analyzedthe histological findings related to vascular injury in nine acutely traumatized human spinal cords obtained at autopsy.The interval from spinal cord injury to death ranged from 20 minutes to 9 months. The microangiograms of the unin-jured human cervical cords demonstrated new information about the sulcal arterial system and the pial arteries. Thecentrifugal sulcal arterial system was found to supply all of the anterior gray matter, the anterior half of the posteriorgray matter, approximately the inner half of the anterior and lateral white columns, and the anterior half of the poste-rior white columns. Traumatized spinal cord specimens in the acute stage (35 days postinjury) showed severe hem-orrhages predominantly in the gray matter, but also in the white matter. The white matter surrounding the hemorrhag-ic gray matter showed a variety of lesions, including decreased staining, disrupted myelin, and axonal and periaxonalswelling. The white matter lesions extended far from the injury site, especially in the posterior columns. There was noevidence of complete occlusion of any of the larger arteries, including the anterior and posterior spinal arteries and thesulcal arteries. However, occluded intramedullary veins were identified in the degenerated posterior white columns. Inthe chronic stage (39 months postinjury), the injured segments showed major tissue loss with large cavitations, where-as both rostral and caudal remote sites showed well-demarcated necrotic areas indicative of infarction mainly in theposterior white columns. Obstruction of small intramedullary arteries and veins by the initial mechanical stress or sec-ondary injury mechanisms most likely produced these extensive white matter lesions. Our studies implicate damage tothe anterior sulcal arteries in causing the hemorrhagic necrosis and subsequent central myelomalacia at the injury sitein acute spinal cord injury in humans.KEY WORDS acute spinal cord injury vascular lesion pathology humans

I

483

to T-2 (two cases) or from C-4 to T-2 (one case) by means of ananterior approach.

The C-5 anterior radiculomedullary artery was cannulated with atapered PE-50 tubing under a dissecting microscope. The cut endsof the anterior spinal artery and other radiculomedullary arteriestransected during removal of the cords were then ligated withNo. 6-0 nylon or No. 4-0 silk. Silicone rubber (Microfil; Flow Tek,Inc., Boulder, CO) was prepared immediately before injection. Thespinal cord was perfused with 1 to 5 ml of saline from the PE-50tubing and 0.7 to 1 ml of silicone rubber was injected manuallythrough a 1-ml syringe for approximately 5 minutes. Following thesilicone rubber injection, the spinal cords were stored in a refriger-ator overnight, after which they were immersed in 10% bufferedformalin for at least 3 weeks.

The vasculature on the surface of the spinal cord was inspectedusing a dissecting microscope. The cord was dehydrated with alco-hol and immersed in methylsalicylate, which rendered the tissuetransparent. The cord was then cut transversely or coronally into 2-mm slices with a razor blade. The cord slices were immersed inmethylsalicylate in a petri dish, and the intramedullary vasculaturewas inspected through a microscope. The course of the intra-medullary vessels could be tracked by changing the microscopicfocus, which allowed a three-dimensional analysis of the vessels inthese 2-mm thick sections.

Histological Analysis of Acute Human Spinal Cord InjuryTo investigate the vascular changes that occur in acute spinal

cord injury, the histological findings in the acutely traumatized spi-nal cords of nine autopsy cases were analyzed. These nine patients,who were aged 10 to 79 years when they died, had suffered com-plete or incomplete cord injury at the cervical level (Table 1). Onepatient died immediately after he had sustained a high cervical cordinjury in a traffic accident. The other eight patients died of pneu-monia, pulmonary embolism, or brainstem infarction 3 days to 9months after they had sustained cervical trauma (Table 1). Thespinal cord specimens were stained with hematoxylin and eosin forgeneral features and luxol fast blue stain for myelinated axons.

ResultsVascular System in the Nontraumatized Cervical Cord

Most of the arterial system on the surface of the non-traumatized spinal cord was completely filled with the sil-icone rubber (Fig. 1 upper), although segments of the pos-terior spinal arteries were only partially filled in two of thecords. Two of the cords also showed filling of the venouschannels on the surface of the cords.

Anterior Surface. The outer layer of the pia mater wasfound to cover the anterior spinal artery and vein on theanterior surface. Two to six anterior radiculomedullaryarteries fed the anterior spinal artery in the examinedsegments. The anterior spinal artery consisted of a singletrunk in one spinal cord and divided into two vessels for ashort distance in the other two spinal cords. The anteriorspinal artery gave rise to sulcal arteries, which travelled inthe anterior median sulcus, and also a few small caliberlateral branches, which traveled over the anterior surfaceof the spinal cord. The sulcal arteries ran into the anteriormedian sulcus and traveled in a slightly rostral direction toenter either the left or right half of the spinal cord (Fig. 1center). Usually a sulcal artery supplied only one side ofthe cord with the adjacent sulcal artery supplying the otherside. A small number of sulcal arteries were found to sup-ply both sides of the spinal cord. The mean number of sul-cal arteries per centimeter of cord in the examined seg-ments was 4.6 (Table 2). There was overlap in the supply

C. H. Tator and I. Koyanagi

484 J. Neurosurg. / Volume 86 / March, 1997

TABLE 1

Clinical features, surgical treatm

ent, and cause of death in nine cases of acute spinal cord injuryA

geInterval

Case(yrs),

From Injury

No.

SexCause of Injury

Level & Type of Injury

Clinical StateSurgical T

reatment

Cause of Death

to Death

110, M

traffic accidentC12 odontoid fracture

com

plete cord injurynone

high cervical cord injury20 m

in2

39, Mtraffic accident

C45 anterior dislocationco

mplete cord injury

open reduction, C45 laminectom

y,

brainstem infarction due to traum

atic3 days

perfusion & m

yelotomy, posterior

occlusion of rt vertebral artery

fusion3

79, Ftraffic accident

C45 fracture dislocationincom

plete cord injury*none

brainstem infarction due to traum

atic 5 days

occlusion of lt vertebral artery

437, M

divingC-7 body fracture

com


acute pulmonary em

bolism17 days

5 65, F

traffic accidentC12 atlantoaxial dislocation

com


acute bronchopneumonia

18 days6

56, Mfall

C45 fracture dislocationco

mplete cord injury

none


3 mos

772, F

traffic accidentC56 fracture dislocation

com

plete cord injuryposterior fusion


3 mos

852, M

traffic accidentC56 anterior dislocation

com



7 mos

970, F

fallC12 odontoid fracture

com

plete cord injuryposterior fusion


9 mos

*Com

plete motor loss w

ith sacral sparing.

so that each segment of gray matter contained capillariesbranching from two to three sulcal arteries. These featurescould be appreciated three-dimensionally in the clearedspecimens. In the anterior sulcus, the sulcal arteries oftenhad small direct branches to the medial anterior whitecolumns. Bifurcation of the sulcal artery was common inthe anterior sulcus: 13 to 28% (mean 19%) of the sulcalarteries bifurcated in the anterior median sulcus. Thesebifurcated sulcal arteries frequently supplied the spinalcord bilaterally, although each branch supplied only one-half of the cord (Table 2).

The lateral branches of the anterior spinal arterycoursed subpially over the anterior and lateral white col-umns. The mean number of these lateral branches was 1.6per centimeter of cord (Table 2). Many of the lateralbranches that reached the lateral columns connected sub-pially with branches of the posterior spinal arteries (Fig. 1lower). Connections between lateral branches of the ante-rior spinal artery themselves also occurred on the lateralsurface of the cord.

The anterior spinal vein ran alongside the anterior spi-nal artery in the anterior aspect of the sulcus, although theanterior spinal vein was generally situated slightly poste-rior to the anterior spinal artery. The anterior spinal veinreceived sulcal veins in the anterior median sulcus andsuperficial veins on the anterior surface.

Posterior Surface. The posterior spinal veins and theposterior spinal arteries were situated on the posterior pialsurface in the subarachnoid space, and arachnoid trabecu-lae were identified along the posterior midline. In contrast,on the anterior surface the anterior spinal artery and veinswere covered by pia mater and there were no trabeculae inthe anterior subarachnoid space. The posterior spinal ar-teries were usually paired arterial channels that ran imme-


Human spinal cord injury

485

FIG. 1. Postmortem photographs of nontraumatized spinal cord.Upper: The anterior surface of the cervical cord. The rostral endis to the left. Silicone rubber was injected into the C-5 radicu-lomedullary artery through tapered PE-50 tubing (arrow). Thearterial and venous channels over the spinal cord surface are almostcompletely filled with silicone rubber. Center: The anterior sur-face and anterior median sulcus of the cervical cord after siliconerubber injection. The pia mater, which covers the anterior spinalartery and vein, has been divided. The rostral end is to the left. Theforceps are holding the pia mater on the anterior surface to open theanterior median sulcus where the sulcal arteries are seen as branch-es of the anterior spinal artery (A). At the posterior end of the ante-rior median sulcus, the sulcal arteries (arrows) course laterally infront of the anterior white commissure and enter either the right orleft half of the spinal cord. Lower: Lateral surface of the spinalcord at the C78 level after silicone rubber injection. The anteriorspinal artery (A) gives rise to a lateral branch (arrow), which thencourses over the anterior and lateral FIG. 1 (continued)

surfaces of the cord. Subsequently, this branch extends subpially(lower arrowhead) under the dentate ligament, which can be dis-cerned as the faint white structure (D), and then communicateswith a small branch from the posterior spinal artery (upper twoarrowheads).

TABLE 2Sulcal arteries and lateral branches of the anterior spinal artery

in three uninjured human spinal cords*Uninjured Spinal Cord

Factor Case 1 Case 2 Case 3 Mean

cord length (cm) 7.0 11.2 4.4 7.5levels C4T1 C3T1 C4C6 NAno. of SAs in cord specimen 29 49 23 33.7no. of SAs/cm 4.1 4.4 5.2 4.6no. of bifurcated SAs (%) 8 (28) 8 (16) 3 (13) 6.3 (19)bilat supply (no. of SAs) 4 5 3 4no. of LBs in cord specimen 7 21 8 12no. of LBs/cm 1.0 1.9 1.8 1.6

* LB = lateral branch of the anterior spinal artery; NA = not applicable;SA = sulcal artery.

The number of sulcal arteries that bifurcated in the anterior median sul-cus.

One of these eight sulcal arteries showed trifurcation. Number of bifurcated sulcal arteries that supplied the spinal cord bilat-

erally.

diately medial or lateral to the posterior root entry zone oneach side and connected with each other over the posteri-or surface through numerous communicating branches.

Intramedullary Vessels. The sulcal arteries supplied allof the anterior gray matter and the anterior part of the pos-terior gray matter (Fig. 2 upper). Branches of the sulcalarteries coursed through the gray matter and then suppliedapproximately the inner half of the anterior and lateralwhite columns (Fig. 2 center). The base of the posteriorwhite columns was also supplied by branches from thesulcal arteries (Fig. 2 right). Approximately the outer halfof the anterior and lateral white columns was supplied bythe centripetal arterial system from the pial arteries. Theposterior spinal arteries and their branches supplied theposterior part of the posterior gray matter and approxi-mately the posterior half of the posterior white columns.

The intramedullary veins were only partially filled withsilicone rubber. The radial veins in the anterior and lateralwhite columns and the posterior septal veins in the poste-rior white columns were identified in two cords.Histological Analysis of Acute Spinal Cord Injury

Immediate Period. In the patient who died approximate-



FIG. 2. Silicone rubber microangiograms of a nontraumatizedspinal cord at the C-8 level after clearing away the tissue. Originalmagnification 3 20. Upper: Transverse view clearly demon-strating intramedullary vessels, although the posterior gray matterand posterior white columns are partially filled. Center: Trans-verse view of the anterolateral spinal cord demonstrating a sulcalartery (SA) supplying the capillary network of the gray matter ofthe anterior horn. The branches of the sulcal artery supply approx-imately the inner half of the lateral and anterior white matter. Theasterisks indicate the watershed zone between the sulcal arterialsystem and the pial arterial system (seen to the left of the asterisks).The arrow indicates extravasated silicone. Lower: Transverseview of the central segment and posterior white columns showingthat the branches (arrows) of the sulcal arteries (SA) extend intothe base of the posterior white columns.

FIG. 3. Case 1. Photomicrographs showing a transverse sectionof the traumatized spinal cord in a patient who died shortly after acomplete cord lesion due to atlantoaxial dislocation. H & E.Upper: The spinal cord at the C-1 level at low magnification showsan almost normal appearance. Original magnification 3 7. Low-er: Higher magnification of this section reveals multiple smallhemorrhages in the anterolateral gray matter. Original magnifica-tion 3 100.

ly 20 minutes after he had been injured in a traffic accident(Case 1), the spinal cord was found to be transected atC12 due to atlantoaxial dislocation and a fractured odon-toid process. Histological sections obtained from the C-1level showed an almost normal appearance except formultiple small hemorrhages in the gray matter (Fig. 3).

Acute Phase. Two patients (Cases 2 and 3) died 3 and 5days, respectively, after they had sustained spinal traumaas a result of brainstem infarction caused by traumaticocclusion of the vertebral artery. The patient in Case 2 hada C45 anterior dislocation and was treated surgically onthe day of injury by open reduction, C45 laminectomy,posterior midline myelotomy, and hypothermic perfu-sion at the injured segment. Histological analysis of thetraumatized segment in this case showed marked in-tramedullary hemorrhage that involved almost the wholespinal cord in the transverse plane (Fig. 4 upper left). Theanterior spinal artery and sulcal artery at this level werepatent, although the anterior spinal artery showed invasion

of polymorphonuclear cells in the endothelial layer. At theadjacent level (approximately C-3) where the dura materwas intact and, hence, distant from the operated seg-ment, the spinal cord showed decreased staining centrallywith intact peripheral white matter (Fig. 4 upper right).The affected white matter in this level was almost totallynecrotic, showing disrupted myelin, enlarged periaxonalspaces, swollen axons, and invasion of polymorphonu-clear cells. Many intramedullary veins in the posteriorwhite columns were occluded and filled with polymor-phonuclear cells (Fig. 4 lower left). The gray mattershowed major stagnation of flow with many small vesselspacked with red blood cells, extravasation of red bloodcells, and invasion of the tissue by polymorphonuclearcells. At the more rostral level (approximately C-2), thenecrotic changes and red cell extravasation were moreconfined to the basal part of the posterior white columnsand focal segments of the lateral white columns (Fig. 4lower right).



487

FIG. 4. Case 2. Photomicrographs displaying transverse sections of the traumatized spinal cord 3 days after completecord lesion due to C45 anterior dislocation. H & E. Upper Left: The injury site (C45 level) shows marked in-tramedullary hemorrhages in the gray and white matter. Original magnification 3 7. Upper Right: The rostral segmentof the cord at approximately the C-3 level shows decreased staining in the gray matter and the central half of the whitematter. There was preservation of the peripheral white matter. There were no hemorrhages. Original magnification 3 7.Lower Left: Higher magnification of a portion of central white matter of the posterior columns of the section shown inupper right. The veins were occluded with polymorphonuclear cells (arrow) and the central white matter was totallynecrotic with many polymorphonuclear cells identified in this area. Original magnification 3 400. Lower Right: A por-tion of the cord farther rostral to that seen in upper right, at approximately the C-2 level. The central areas of decreasedstaining are much smaller than those seen in upper right and were confined to the base of the posterior white columnsand part of the lateral white matter. Original magnification 3 7.

In Case 3, in which the patient had suffered a C45 frac-ture dislocation and an incomplete cord lesion (completeloss of distal motor function, but sparing of sacral sen-sation), the gray matter of the injured segment showednumerous hemorrhages and the white matter surroundingthe hemorrhagic gray matter showed extensive necrosis(Fig. 5). Much of the peripheral white matter showed amore normal appearance with persisting myelinated axonsin the subpial rim of tissue. There was no evidence ofocclusion of the anterior spinal artery or sulcal arteries.

Subacute Phase. The patient in Case 4 died of acute pul-monary embolism at 17 days and the patient in Case 5died of acute bronchopneumonia at 18 days after sustain-ing spinal trauma. Cases 4 and 5 did not show any dis-cernible normal white matter at the injury site, even in thesubpial rim. The tissue was completely replaced by lipid-laden phagocytic cells that frequently contained hemo-siderin. Many dilated small vessels were also identified(Fig. 6), which were most likely new vessels proliferatinginto the necrotic tissue. At adjacent levels, the white mat-ter showed varying degrees of degeneration with a varietyof degenerative axonal changes, including enlargement ofthe periaxonal spaces and swollen giant axons.

Chronic Phase. Four patients (Cases 69) died of pneu-monia 3 to 9 months after they had sustained trauma. Intwo of these patients (Cases 6 and 7), the spinal cord at theinjured segment showed complete necrosis with virtuallyno identifiable normal gray or white matter even at thesubpial rim (Fig. 7 upper), although there was some glio-sis and many phagocytic cells. In two patients (Cases8 and 9), there was some remaining peripheral white mat-ter. At the adjacent rostral and caudal segments, 1 to 2cm remote from the injury site, the base of the posteriorcolumns contained clearly demarcated areas of necrosisthat were highly suggestive of discrete infarcts (Fig. 7lower). In these remote necrotic areas, there was no evi-

dence of previous hemorrhage such as deposits of hemo-siderin. Similar remote discrete infarcts were also ob-served in the lateral white matter in one case. Clusters andnests of proliferating Schwann cells were observed in theposterior and anterior white columns at the injury site intwo cases (Cases 8 and 9).

DiscussionBlood Supply to the Human Spinal Cord

The aim of examining the blood supply to the humanspinal cord using three-dimensional silicone rubber mi-croangiography was to obtain information for determiningthe pathophysiology of major vascular lesions in humanspinal cord injury. There have been many excellent stud-ies of the blood supply of the human spinal cord, whichhave demonstrated the centrifugal supply from the sulcalarteries, the centripetal supply from the posterior spinaland pial arteries, and the intervening watershed zonessupplied through both routes.3,12,14,15,22,4043 The presentthree-dimensional study confirms this arrangement. Wealso demonstrated the origin of the pial arteries as lateralbranches from the anterior spinal artery and that thesecommunicate extensively with lateral branches originat-ing from the posterior spinal arteries. The sulcal arteries,which number approximately four to five per centimeterof cervical cord, often bifurcate in the anterior median sul-cus. These findings are also similar to those described byother authors.42,43 However, the descriptions of the patternof the intramedullary arterial supply in the human spi-nal cord have differed among the authors. According toTurnbull and colleagues41,42 and Lazorthes, et al.,22 the sul-cal arteries supply most of the gray matter and also thebase of the posterior white columns (Fig. 8). These au-thors showed that the overlap between the zones of supplyfrom the centrifugal sulcal arteries and the centripetalpenetrating arteries is located at the junction of the outerborder of the gray matter and adjacent white matter.



FIG. 5. Case 3. Photomicrograph showing the traumatizedspinal cord at the C-4 level 5 days after an incomplete cord injurydue to a C45 fracture dislocation. Multiple hemorrhages are con-fined to the gray matter. The white matter adjacent to the hemor-rhagic gray matter shows decreased staining, whereas the subpialperipheral white matter of the lateral and posterior columns ispreserved. H & E and luxol fast blue, original magnification 3 7.

FIG. 6. Case 4. Photomicrograph showing the traumatizedspinal cord 17 days after complete cord injury due to C-7 bodyfracture. The gray matter of the injured segment contains manyphagocytic cells with foamy cytoplasm. Dilated small vessels(arrows) are also identified. There are no persisting neurons.H & E, original magnification 3 400.

Furthermore, these reports showed that most of the whitelateral columns are supplied only by the penetratingbranches from the pial arterial plexus. In contrast, accord-ing to Gillilans12 study, the penetrating arteries from thepial arteries supply the outer rim of the white matter andthe overlapping area, which is much larger than that foundby Turnbull and colleagues, and comprises the outer rimof the gray matter and the inner two-thirds of the whitematter in the lateral and anterior spinal cord (Fig. 8).Herren and Alexander15 reported that the lateral cortico-spinal tract is nourished by branches of the sulcal arteries,a finding supported by the present study. Although someof the differences in observations by previous investiga-tors might be due to variations in vasculature in differentspinal cord specimens, it is more likely that the discrepan-cies are due to the difficulties in differentiating arteriesfrom veins inherent in the postmortem two-dimensionalmicroangiographic techniques used in previous studies.

The lack of three-dimensional observation is also likely tohave produced misinterpretation of the zones of supply. Incontrast, the three-dimensional silicone rubber microan-giographic technique used in the present study allowsaccurate mapping of the extent of supply and also is ofmajor benefit in differentiating arteries and veins. Also,our injection technique fills mainly the arterial system andcapillaries; this aided our differentiation between arteriesand veins. The present results prove that the sulcal arteri-al system supplies all the anterior gray matter, the anteriorhalf of the posterior gray matter, approximately the innerhalf of the anterior and lateral white matter columns, andthe anterior half of the posterior white columns (Fig. 8). Itis of interest that the distribution of peripheral white mat-ter lesions caused by a pial arterial circulatory disturbance



489

FIG. 7. Case 7. Photomicrographs displaying the traumatizedspinal cord 3 months after complete cord injury due to C56 frac-ture dislocation. Upper: The injured segment shows markednecrosis and disorganization with virtually no identifiable graymatter. The anterior spinal artery at the lowermost aspect of thespecimen was patent. Lower: A rostral segment of the cord atapproximately C-3. Well-demarcated necrotic areas (arrows),which have the appearance of circumscribed infarcts, are seen atthe base of the posterior white columns. The more external portionof the posterior white columns shows Wallerian degeneration. H &E and luxol fast blue, original magnification 3 7.

FIG. 8. Diagrams displaying patterns of arterial supply in thenormal human cervical cord. The central area is supplied by thecentrifugal arterial system composed of branches of the sulcal ar-teries (SA). The peripheral white matter and the posterior portionof the posterior gray matter are supplied by the centripetal arterialsystem composed of branches of the posterior spinal arteries andthe pial arteries (PA). The shaded area shows the overlap or water-shed zone between the centrifugal and centripetal arterial systems.Note the differences in the patterns of arterial supply between pre-vious authors and the present study. The present findings indicatethat the centrifugal system supplies most of the gray matter and themedial white matter of the anterior, lateral, and posterior whitecolumns.

in the two autopsy cases of systemic lupus erythematosusreported by Nakano, et al.,25 is consistent with our findingsconcerning the pattern of vascular supply in the cord.

Histology and Pathophysiology of Vascular Lesions inHuman Spinal Cord Injury

Although the present study included only one case ex-amined in the 1st hour after injury, in the literature thereare several cases examined within the first 24 hours aftersevere spinal cord injury that have shown petechial andmore confluent hemorrhages in much of the gray mat-ter. The absence of cellular and tissue necrosis in the ear-ly period has been reported in several studies of humanspinal cord injury.1618,23 Thereafter, there is evidence fora progressive necrotizing process. In the present study,specimens examined 3 to 5 days after injury showedsevere tissue necrosis and an inflammatory cell infiltrationthat affected the gray matter and extended out into thewhite matter. Our study confirmed that none of the majorarteries on the surface of the human spinal cord, includingthe anterior and posterior spinal arteries, are occluded atthe injury site or remotely at any time after trauma. Thisfinding corresponds to those of our previous microangio-graphic studies20,21,45 in a rat model of spinal cord injury inwhich there was extensive occlusion and vasospasm ofintramedullary vessels, but patency of the large arteries atall times after injury. Jellinger16 also reported that in hu-man spinal cord injury traumatic occlusion or thrombosisof the major arteries on the surface of the cord is extreme-ly rare. These findings lead to the conclusion that the loca-tion of vascular damage in human spinal cord injury is pri-marily in the intramedullary vascular system.

It is of major interest that the supply territory of the sul-cal arteries, as defined by the microangiographic study,corresponds very closely to the distribution of both thehemorrhagic necrosis in the acute phase and the centralmyelomalacia and cavitation of the later phases, whichinvolve most of the gray matter and at least the inner halfof the white matter of the anterior, lateral, and posteriorcolumns. Thus, the site of the major arterial injury impli-cated in acute spinal cord trauma is the anterior sulcalartery within a short distance from its origin at the anteri-

or spinal artery. To produce the extensive bilateral areas ofdamage in the rostralcaudal plane, which were seen inmost of the cases of acute spinal cord injury examined inthe present study, would require damage to several anteri-or sulcal arteries because these arteries supply alternatesides of the cord and overlap with two or three sulcalarteries supplying each destination. We found an averageof 4.6 sulcal arteries per centimeter of cord and estimatethat to produce a complete cord injury, such as that shownin Fig. 4 upper right, would likely involve damage toapproximately 1 cm of cord tissue containing two or threesulcal arteries supplying blood to each side. Incompletecord injuries, such as that shown in Fig. 5, might occurfrom shorter lengths of damaged cord containing only oneor two sulcal arteries on each side. Occlusion of the sulcalarteries more distally would allow greater preservation ofthe anterior parts of the cord (Fig. 5), which would con-tinue to receive blood through persisting small branchesof the sulcal artery arising in the anterior median sulcus.Thus, our findings also suggest that less severe injurieswould damage the sulcal arteries distally, whereas moresevere injuries would damage the sulcal arteries proxi-mally. The exact nature of the arterial damage could bedirect mechanical damage or a secondary process such asvasospasm.

It is acknowledged that there are alternative explana-tions for central hemorrhagic necrosis and central myelo-malacia. For example, it could be hypothesized that theprinciple anatomical site of vascular injury is the endothe-lial cells of capillaries, either by direct mechanical traumaor secondary to ischemia. In turn, endothelial cell damagewould result in hemorrhage and then infarction. However,this concept of endothelial cell capillary damage is lessconsistent with the anatomical distribution of central hem-orrhagic necrosis and myelomalacia than the sulcal arteryhypothesis.

In the present study, at the injury site the gray matterwas more prone to be hemorrhagic, whereas most ofthe white matter showed nonhemorrhagic degenerativechanges including decreased staining, periaxonal and ax-onal swelling, and disruption of myelin in the acute stage(35 days postinjury). These white matter lesions weredistributed around the hemorrhagic gray matter and ex-tended rostrally and caudally from the injury site, espe-cially in the posterior white columns. It is highly likelythat these nonhemorrhagic white matter lesions progressin time to become the well-demarcated necrotic whitematter areas in the later stages that have the histologicalappearance of infarcts. The predominance of hemorrhagesin the gray matter can be explained on the basis of the richcapillary network in the gray matter, the latter being high-ly susceptible to mechanical stress because of its looser,more yielding texture. The surrounding white matter le-sions may be partly explained by the centrifugal vascularsupply of the sulcal arteries. As noted above, silicone rub-ber microangiograms showed that the inner half of thewhite matter was predominantly supplied by small arteri-al branches from the sulcal arteries, which course throughthe gray matter to reach the white matter. Thus, it is high-ly likely that interference with the sulcal centrifugal arte-rial system in the gray matter leads to a subsequent inter-ruption of blood flow to the inner half of the white matter.Similar to the above discussion about proximal and distal



FIG. 9. Diagram showing vessels that would be affected to pro-duce the histological appearance of major central necrosis (stippledarea) with a subpial rim of surviving white matter. Hemorrhagesare not shown. The lines across the arrows indicate damaged ves-sels. ASA = anterior spinal artery; PSA = posterior spinal artery;SA = sulcal artery.

sulcal artery damage, the possible mechanisms of interfer-ence with these en passage smaller branches of the sul-cal arteries would include direct mechanical or secondarydamage (Fig. 9). There is experimental evidence for theconcept of secondary vascular damage involving thecentripetal sulcal system. For example, we found a directrelationship between hemorrhagic gray matter and adja-cent ischemic zones in the white matter in rats after acuteclip-compression injury studied with colloidal carbonangiography.45 Also, our laboratory previously showedvasospasm of the sulcal arteries20 in similarly injured ratsstudied with polyester resin and scanning electron mi-croscopy.

Our laboratory and others have also postulated thatischemia of the posterior white columns can be producedby disturbances of venous drainage in the acutely trau-matized spinal cord.20,21,35,36 Support for this hypothesiscomes from observations that venous occlusion in thespinal cord in various pathological conditions causes pre-dominantly white matter lesions.19,28,30 With a weight-dropmodel of mild spinal cord injury, Dohrmann and associ-ates6 reported that disruption of the muscular venules inthe gray matter occurs early after trauma in primates.In the present study, we found occluded veins filledwith polymorphonuclear cells in the degenerated posteri-or white columns in the acute stage (Case 2). However, itwas not possible to determine whether the venous occlu-sion was caused by direct mechanical damage of the veinsor was secondary to arterial or capillary occlusion. Inour opinion, it is highly likely that venous damage, eitherdirect or secondary, contributes significantly to the non-hemorrhagic white matter lesions. Our previous studies ofveins in rats with spinal cord injury using silicone rub-ber angiography demonstrated several anatomical featuresthat make these veins suceptible to occlusion during com-pression injury.21 Unfortunately, the present study did notprovide sufficient opportunity to study the anatomy of thevenous drainage to determine if there are similar anatom-ical features in the human cord.

The distribution of mechanical stress in the traumatizedspinal cord could be another important factor affecting thevasculature to cause the extensive white matter lesions.Blight and Decrescito2 used silastic tubing filled withgelatin as a physical model of the spinal cord to demon-strate that an anteroposterior compressive force on thetube produces longitudinal stress that is most intense inthe center of the tube. Because the pia mater is a strongmembrane, the large vessels on the surface of the spi-nal cord and in the anterior median sulcus would be rela-tively spared from major damage due to mechanicalstress exerted in the anteroposterior direction. However,the smaller intramedullary vessels would be stretched inthe longitudinal plane. Differences in compliance in thespinal cord may produce a shearing stress on microvesselsthat form a bridge between the gray and white matter.Such a stretching force and shearing stress may obstructthe microvessels directly, or initiate secondary pathologi-cal responses in the vascular walls, such as platelet aggre-gation or invasion by polymorphonuclear cells, whichsubsequently lead to vascular occlusion.

McVeigh24 postulated that necrotic, pulped spinal cordtissue produced in the traumatized segment could invadelongitudinally and travel rostrally and caudally in the cen-

ter of the cord. He considered that the remote lesions inthe posterior white columns are caused by invasion of thepulped mass. We saw no evidence of this process in ourcases. For example, there was no evidence of hemorrhag-ic tissue in these remote areas of necrotic white matterin the acute stage, and there was no evidence of previoushemorrhage in the necrotic white matter in the chronicstage.

Recently, Quencer, et al.,29 and Bunge, et al.,4 reportedexcellent studies of the pathological findings of thetraumatized spinal cord in humans. In particular, theyshowed a lack of hemorrhage in the gray and white matterin several cases of central cord syndrome. Instead, theyfound major axonal injury in the lateral corticospinaltracts which they attributed to anteroposterior compres-sion forces. Although they did not mention the possibilityof a vascular mechanism of injury, our studies suggest thatstretching or compression of the centrifugal sulcal branch-es might result in occlusion or constriction of these vesselssupplying the corticospinal tracts.

Further investigation is necessary to elucidate thepathophysiology of hemorrhagic gray matter lesions andnonhemorrhagic white matter lesions in acute spinal cordinjury in humans. To date, our investigations provideevidence of the importance of the centrifugal sulcal arte-rial system, which may be the principal site of the prima-ry direct mechanical injury and the secondary mecha-nisms of injury, some of which (such as vasospasm) maybe delayed and amenable to treatment.

Acknowledgments

We thank Dr. John H. N. Deck, Division of Neuropathology,Department of Pathology, The Toronto Hospital, for providing thehistological material in the cases of acute spinal cord injury, and Dr.Peter Dirks for helping to prepare the cervical cord specimens formicroangiography. Grateful acknowledgement is also made to Mr.Jim Loukides for his technical assistance.

References

1. Allen WE III, DAngelo CM, Kier EL: Correlation of microan-giographic and electrophysiologic changes in experimentalspinal cord trauma. Radiology 111:107115, 1974

2. Blight AR, Decrescito V: Morphometric analysis of experimen-tal spinal cord injury in the cat: the relation of injury intensityto survival of myelinated axons. Neuroscience 19:321341,1986

3. Bolton B: The blood supply of the human spinal cord. J NeurolPsychiatry 2:137148, 1939

4. Bunge RP, Puckett WR, Becerra JL, et al: Observations on thepathology of human spinal cord injury. A review and classifi-cation of 22 new cases with details from a case of chronic cordcompression with extensive focal demyelination. Adv Neurol59:7589, 1993

5. Dohrmann GJ, Allen WE III: Microcirculation of traumatizedspinal cord. A correlation of microangiography and blood flowpatterns in transitory and permanent paraplegia. J Trauma 15:10031013, 1975

6. Dohrmann GJ, Wagner FC Jr, Bucy PC: The microvasculaturein transitory traumatic paraplegia. An electron microscopicstudy in the monkey. J Neurosurg 35:263271, 1971

7. Dohrmann GJ, Wick KM, Bucy PC: Spinal cord blood flow pat-terns in experimental traumatic paraplegia. J Neurosurg 38:5258, 1973

J. Neurosurg. / Volume 86 / March, 1997 491


8. Fairholm DJ, Turnbull IM: Microangiographic study of experi-mental spinal cord injuries. J Neurosurg 35:277286, 1971

9. Fehlings MG, Tator CH, Linden RD: The effect of nimodipineand dextran on axonal function and blood flow following ex-perimental spinal cord injury. J Neurosurg 71:403416, 1989

10. Fehlings MG, Tator CH, Linden RD: The relationship amongthe severity of spinal cord injury, motor and sensory evoked po-tentials and spinal cord blood flow. Electroencephalog ClinNeurophysiol 74:241259, 1989

11. Fried LC, Goodkin R: Microangiographic observations ofthe experimentally traumatized spinal cord. J Neurosurg 35:709714, 1971

12. Gillilan LA: The arterial blood supply of the human spinal cord.J Comp Neurol 110:75103, 1958

13. Guha A, Tator CH, Rochon J: Spinal cord blood flow and sys-temic blood pressure after experimental spinal cord injury inrats. Stroke 20:372377, 1989

14. Hassler O: Blood supply to human spinal cord. A microangio-graphic study. Arch Neurol 15:302307, 1966

15. Herren RY, Alexander L: Sulcal and intrinsic blood vesselsof human spinal cord. Arch Neurol Psychiatry 41:678687,1939

16. Jellinger K: Neuropathology of cord injuries, in Vinken PJ,Bruyn GW (eds): Handbook of Clinical Neurology. Vol 25:Injury of the Spine and Spinal Cord. Part 1. Amsterdam:North-Holland, 1976, pp 43121

17. Kakulas BA: Pathology of spinal injuries. Cent Nerv SystTrauma 1:117129, 1984

18. Kakulas BA, Taylor JR: Pathology of injuries of the vertebralcolumn and spinal cord, in Vinken PJ, Bruyn GW, KlawansHL, Frankel HL (eds): Handbook of Clinical Neurology. Vol61: Spinal Cord Trauma. Amsterdam: North-Holland, 1992,pp 2151

19. Kim RC, Smith HR, Henbest ML, et al: Nonhemorrhagic ve-nous infarction of the spinal cord. Ann Neurol 15:379385,1984

20. Koyanagi I, Tator CH, Lea PJ: Three-dimensional analysis ofthe vascular system in the rat spinal cord with scanning electronmicroscopy of vascular corrosion casts. Part 2: Acute spinalcord injury. Neurosurgery 33:285292, 1993

21. Koyanagi I, Tator CH, Theriault E: Silicone rubber microan-giography of acute spinal cord injury in the rat. Neurosurgery32:260268, 1993

22. Lazorthes G, Gouaze A, Zadeh JO, et al: Arterial vasculariza-tion of the spinal cord. Recent studies of the anastomotic sub-stitution pathways. J Neurosurg 35:253262, 1971

23. Liss L: Fatal cervical cord injury in a swimmer. Neurology 15:675677, 1965

24. McVeigh JF: Experimental cord crushes with especial referenceto the mechanical factors involved and subsequent changes inthe areas of the cord affected. Arch Surg 7:573600, 1923

25. Nakano I, Mannen T, Mizutani T, et al: Peripheral white matterlesions of the spinal cord with changes in small arachnoid ar-teries in systemic lupus erythematosus. Clin Neuropathol 8:102108, 1989

26. Nelson E, Gertz SD, Rennels ML, et al: Spinal cord injury. Therole of vascular damage in the pathogenesis of central hemor-rhagic necrosis. Arch Neurol 34:332333, 1977

27. Nemecek S: Morphological evidence of microcirculatory dis-turbances in experimental spinal cord trauma. Adv Neurol 20:395405, 1978

28. Ohshio I, Hatayama A, Kaneda K, et al: Correlation betweenhistopathologic features and magnetic resonance images of spi-nal cord lesions. Spine 18:11401149, 1993

29. Quencer RM, Bunge RP, Egnor M, et al: Acute traumatic cen-tral cord syndrome: MRI-pathological correlations. Neurora-diology 34:8594, 1992

30. Rao KR, Donnenfeld H, Chusid JG, et al: Acute myelopa-thy secondary to spinal venous thrombosis. J Neurol Sci 56:107113, 1982

31. Reed JE, Allen WE III, Dohrmann GJ: Effect of mannitol on thetraumatized spinal cord. Microangiography, blood flow pat-terns, and electrophysiology. Spine 4:391397, 1979

32. Rivlin AS, Tator CH: Regional spinal cord blood flow in ratsafter severe cord trauma. J Neurosurg 49:844853, 1978

33. Sandler AN, Tator CH: Review of the effect of spinal cord trau-ma on the vessels and blood flow in the spinal cord. J Neuro-surg 45:638646, 1976

34. Sasaki S: Vascular change in the spinal cord after impact injuryin the rat. Neurosurgery 10:360363, 1982

35. Schneider H: Acute and chronic pathomorphological reactionsto cord injury. in Schramm J, Jones SJ (eds): Spinal CordMonitoring. Berlin: Spring-Verlag, 1985, pp 103120

36. Shingu H, Kimura I, Nasu Y, et al: Microangiographic study ofspinal cord injury and myelopathy. Paraplegia 27:182189,1989

37. Tator CH: Ischemia as a secondary neural injury, in SalzmanSK, Faden AI (eds): The Neurobiology of Central NervousSystem Trauma. New York: Oxford University Press, 1994,pp 209215

38. Tator CH: Review of experimental spinal cord injury with em-phasis on the local and systemic circulatory effects. Neuro-chirurgie 37:291302, 1991

39. Tator CH: Spinal cord cooling and irrigation for treatment ofacute cord injury, in Popp AJ, Bourke RS, Nelson LR, et al(eds): Neural Trauma. Seminars in Neurological SurgerySeries. New York: Raven Press, 1979, pp 363369

40. Tator CH, Fehlings MG: Review of the secondary injury theo-ry of acute spinal cord trauma with emphasis on vascular mech-anisms. J Neurosurg 75:1526, 1991

41. Turnbull IM: Microvasculature of the human spinal cord. JNeurosurg 35:141147, 1971

42. Turnbull IM, Brieg A, Hassler O: Blood supply of cervical spi-nal cord in man. A microangiographic cadaver study. J Neu-rosurg 24:951965, 1966

43. Tveten L: Spinal cord vascularity. III. The spinal cord arteriesin man. Acta Radiol (Diagn) 17:257273, 1976

44. Vlajic I: Microangiographic observations of morphological ves-sel changes after experimental spinal cord trauma. Adv Neurol20:451460, 1978

45. Wallace MC, Tator CH, Frazee P: Relationship between post-traumatic ischemia and hemorrhage in the injured rat spinalcord as shown by colloidal carbon angiography. Neurosurgery18:433439, 1986

Manuscript received September 18, 1995.Accepted in final form September 24, 1996.This work was supported by the Canadian Paraplegic Asso-

ciation, Ontario Branch; the Samuel Lunenfeld Research Foun-dation; and the Medical Research Council of Canada. During thecourse of this study, Dr. Koyanagi was a Fellow of the Rick HansenMan in Motion Legacy Fund.

Address for Dr. Koyanagi: University of Hokkaido School ofMedicine, Sapporo, Japan.

Address reprint requests to: Charles H. Tator, M.D., Ph.D.,Division of Neurosurgery, The Toronto Hospital, Western Division,399 Bathurst Street, McLaughlin Pavilion 2-435, Toronto, Ontario,M5T 2S8 Canada.



mecanismo vascular en tvm

Documents

acute spinal cord injury

traumatized human spinal

traumatized spinal cord

canadau vascular injury

secondary injury mechanisms

secondary neural injury

severe spinalcord injury

vascular mechanisms