Morphologic Changes in Arteries and Brain Substance in Traumatic Subarachnoid Hemorrhage

Savchuk A.N., Svistov D.V., Matsko D.E.

Chair of Neurosurgery, Medicomilitary Academy, Saint Petersburg, Russia


Research of the last years has brought about a new understanding of mechanisms, causing development of constrictive-stenotic arteriopathy (CSA) in patients with aneurysmal subarachnoid hemorrhage (SAH). On the one hand, morphologic studies, which has revealed structural changes in walls of cerebral arteries and has been carried out mainly in aneurysmal SAH, allow to explain existing torpidity of CSA in relation to spasmolytic therapy. On the other hand, they serve grounds for discussing rightfulness of the term spasm, used for description of this process [3, 4]. R. Seiler reports structural changes of a vascular wall and stages of a spasm course after aneurysm rupture. According to a character of destructive-reparative processes, he distinguishes 5 stages of changes, which take place in a vascular wall: 1 - contraction of an internal elastic membrane (IEM) and intima's edema; 2 - necrosis of smooth muscle fibers in tunica media, partial rupture of IEM and spread of areas with marked accumulation of acidic mucopolysaccharides; 3 - intima's thickening and atrophy of a median layer; 4 - thinning of internal layers of a vascular wall; 5 - regeneration of smooth muscle fibers in a median layer. Depending on spasm severity, these changes in a wall of a damaged vessel develop within 4-100 days after hemorrhage [13].

T.M. Vikhert et al. consider, that vasospasm develops against a background of existing destructive changes in arterial walls, manifesting themselves in subendothelial fibrosis and lesion of IEM (stratification, thickening, folding disorders) [1].

N.F. Kassell sticks to the opinion, that a percentage of causes, leading to constriction of a vascular lumen is as follows: persistent contraction of smooth muscles - 90%, changes of wall's architectonics - 5% and thromboembolism and other causes - 5% [9]. Papadopoulos et al. do not deny a role of the second cause, mentioned by Kassell, but they give priority to an active component, i.e. contraction of smooth muscles due to an effect of Ca++ and protein-kinase [12].

Morphologic findings in damaged cerebral vessels and groundlessness of the notion spasm led to appearance of several new terms: constrictive endarteriopathy [6], vasculopathy [5], vasoconstrictive arteriopathy [12], constrictive angiopathy [2]. According to our opinion, the term constrictive-stenotic angiopathy, proposed by Yu.A. Medvedev, Yu.N. Zubkov and Zh.Z. Zakaryavichus in 1995, reflects detected morphologic findings to the utmost.

Today there are only two studies, describing morphologic changes in vessels of patients with posttraumatic vasospasm. J. Hughes presented information on changes in vessels of 10 cases, who died of craniocerebral trauma. Unfortunately, vasospasm in this group was not confirmed by clinical methods. The authors classified changes in a vascular wall into 4 categories: atrophy of a median layer and thickening of a subendothelial layer by more than 0.2 mm; thickening of a subendothelial layer by 0.1-0.2 mm; thickening of a subendothelial layer by 0.1 mm; absence of both convincing atrophy of a muscular layer and complete encirclement of a lumen by subendothelial fibrosis [8].

A. Yu. Zubkov et al. studied morphologic changes in a vascular wall of patients with craniocerebral trauma, who were examined with the help of transcranial Doppler for vasospasm diagnosis. The results were indicative of apoptosis and desquamation of endothelial cells, marked thickening of a subintimal layer and media fibrosis [15].

The goal of our study was to estimate morphologic changes in arterial walls of patients with severe craniocerebral trauma and constrictive-stenotic arteriopathy, diagnosed during life time.

Materials and Methods

Morphologic changes were assessed with light and electron microscopy. Fragments of basal arteries were excised in autopsy of 6 patients. Dopplerographic and angiographic examinations, carried out when they had been alive, were indicative of CSA. Fatal outcomes occurred on the 7th, 8th and 9th day in 3, 2 and 1 patients respectively. A progradient type of a CSA course was watched in 2 cases; 4 patients had an apoplectiform type. A postmortem examination and excision of specimens for microscopic studies took place during the first day since death. Intensive care in 1 patient was accompanied by performing transluminal balloon angioplasty (TBA).


Light Microscopy (General and Semi-Thin Sections).

Pathologic changes were detected in all layers of a vascular wall. The most frequent phenomenon was a lesion of endothelium. There were changes in a form and orientation of endotheliocytes, as well as their total and partial desquamation (Fig.1), (Fig.2), (Fig.3). Endotheliocytes had vertical orientation in relation to IEM. There was partial or complete desquamation of endothelium with an exposed subendothelial layer, caused by impaired intercellular relations and relationship with a basal membrane. Watched reactive changes in exposed intima (leukocytic infiltration, appearance of isolated phagocytes, etc.), as well as parietal thrombogenesis, were regarded to be vital signs of a pathologic process (Fig.2), (Fig.4).

A basal membrane was characterized by degenerative changes, varying from its thinning up to complete disappearance. It thickened in some areas and formed flask-like distensions (Fig.5).

One of the main versions of morphologic changes was formation of longitudinal folds on a vascular wall. They protruded into a vascular lumen and constricted it by half. Thus, a lumen acquired a star-shaped view with a scalloped internal perimeter. This phenomenon was caused by changes within a muscular layer and characterized by marked twisting of IEM (Fig.1), (Fig.6). As for alterations within IEM, they were represented by stratification, fiber disintegration, greater twisting and sometimes thickening (Fig.2), (Fig.5).

There were distinctive changes within a muscular layer as well. All autopsied specimens of arteries were characterized by deformed myocyte nuclei, whose lengthened oval shape became either round or irregular (Fig.7), (Fig.9).

Media folds had a shape of oval and round protrusions on transverse sections. They conditioned twisting of an internal outline of a damaged vessel. Myocytes within these folds lost their characteristic orientation. Myocyte fascicles were stretched out and pressed to each other at the bottom of these protrusions. There were disorientation of muscular fibers in some folds, their dystrophic and necrotic changes (focal micromedianecrosis) (Fig.6). One could watch diffuse edema and stratification of intermuscular spaces (empty zones between them) in a muscular layer, typical of all studied specimens. Formation of collagen fibers in a muscular layer of some folds was indicative of initial media sclerosis (Fig.8), (Fig.9).

Structural changes in an external membrane (adventitia) were minimum. There were edema, minor leuko- and lymphocytic infiltration. Diffuse edema, which involved intima and media together with advintitia, resulted in thickening of arterial walls and further aggravation of a stenotic effect.

According to our observation, analogous morphologic changes were typical of perforating branches too (see changes in application of scanning electron microscopy, described below).

Light microscopy was used for studying brain substance in 5 patients, whose postmortem examination revealed foci of softening and/or edema in areas of blood supply of arteries with verified CSA. Besides, it was indicative of a focal degenerative-necrotic process of a vascular origin, which had a tendency to fusion (Fig.10). There were different stages of hypoxic changes, watched in neurons. They varied from acute swelling and contraction with manifestations of neuronophagia up to appearance of areas with absent neurons against a background of edematous changes of neuropilos (Fig.11). Some cases had moderate round-cell perivascular infiltration (Fig.12), (Fig.13). Partial or complete degeneration of glial fibers was observed. When death occurred on the 8-9th day, a morphologic picture corresponded to that of brain infarction. A peripheral zone of ischemia contained isolated lymphocytes and macrophages. In case of involvement of the brain stem into an ischemic process, neurons of its nuclei were characterized by the whole spectrum of dystrophic changes, ranging from swelling up to granule-body degeneration (Fig.14), (Fig.15).

Electron Microscopy.

Scanning and transmission electron microscopy revealed pathologic changes in an arterial wall, which correlated with the above-mentioned findings. The most typical of them consisted in damage and desquamation of endothelium, thrombocyte aggregation and fibrin accumulation in damaged endothelium, thickening of a muscular layer and intima, myocyte necrosis, fibroblast proliferation (Fig.16), (Fig.17), (Fig.18), (Fig.19). There were folding of an internal surface, edema of all layers of an arterial wall, infiltration by isolated leukocytes, sedimentation of isolated granules of hemosiderin. As for a subendothelial space, one could see isolated vesicles. Some areas of IEM were thinned; its complete absence was watched at a rather considerable length. Its outlines, facing media, were clear and even and those, facing endothelium, were wavy and vague in some places (Fig.21). Transverse sections of folds showed, that IEM was stratified both at their root and top. Studying media demonstrated a preserved even outline of a cytoplasmic membrane in the majority of cells. Cytoplasm of some myocytes was clear; myofibrils were almost indistinct or subject to focal lysis. There were dystrophic changes of myocytes, manifesting themselves in accumulation of lipid vacuoles of a different size in their cytoplasm (Fig.20), (Fig.21). Fiber disintegration, caused by interstitial edema, was watched in an external arterial membrane.

Studying a surface of perforating arteries with scanning electron microscopy revealed beads-like folding (Fig.23). Examination of IEM in a scanning mode showed its folding, resulting in a stenosed lumen of a vessel opening (Fig.24). These disorders were observed by us in all 4 cases with an apoplectiform clinical course.

Thus, morphologic changes in basal arteries were typical practically of all layers of arterial walls in CSA, diagnosed during life time. They resembled disorders, observed in aneurismal SAH, to a considerable extent. At first, constriction of arterial lumens in CSA was caused by spasm of smooth muscles. Subsequent transition to their prolonged constriction was conditioned by development of reactive-inflammatory, necrotic and proliferative-substituting processes. Partial or complete desquamation of endotheliocytes, impairment of their orientation ("raising upright", Fig.22) and intercellular relationships promoted parietal thrombus formation (Fig.17). Besides, CSA was characterized by folding of an elastic membrane and formation of invaginating longitudinal folds of intima, necrosis and connective tissue vegetations within a muscular layer (Fig.16), (Fig.18). Edema and thickening of an intima-media complex aggravated a stenotic component of tonic contractions. Typical morphologic changes were watched in perforating arteries, supplying the brain stem, as well. In its turn, parietal thrombus formation in major basal vessels could result in microembolism of intracerebral arteries.

Changes in brain substance consisted in development of an ischemic lesion of different severity, ranging from reversible up to macroscopically visible infarctions.

Morphologic study of arteries and brain substance in a patient with critical CSA, who had underwent balloon angioplasty on the 3rd-4th day after ischemia, revealed no folding of IEM and constriction of an arterial lumen, typical of CSA. But there were desquamation of endotheliocytes with an exposed subendothelial layer, parietal thrombus formation and thinning of a basal membrane. One could watch dead isolated myocytes in a muscular tunic (Fig.25), (Fig.26).

There were degeneration of brain substance (ischemic microinfarctions) in a region of blood supply of damaged arteries and areas of necrosis in the brain stem. Swelling and neuron contraction in an ischemic zone, pericellular and perivascular edema were present. In our opinion, ischemic changes in brain substance developed because of delayed TBA.


Constriction of lumens of basal arteries in cases, who had died of severe craniocerebral trauma and had CT-verified SAH, was conditioned by reactive-inflammatory, necrotic and proliferative-substituting processes. They manifested themselves in marked endothelium desquamation, parietal thrombus formation, edema, thickening, sclerosis, pathologic folding and protrusion of an intima-media complex into an arterial lumen. Morphologic changes, typical of CSA, were watched not only in major, but also in perforating arteries, supplying the brain stem with blood. Thus, parietal thrombi and desquamated endothelium can be a cause of microembolism (at least, hypothetically), which, in its turn, can aggravate ischemia, conditioned by CSA, and effect a course and outcome of severe craniocerebral trauma.

As for patients with symptomatic CSA, absence of typical folding and artery stenosis after angioplasty is indicative of possible use of TBA at the earliest stage of secondary ischemia development, i.e. before appearance of gross and irreversible morphologic changes.


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