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The cerebral blood-vessels in health and disease. By Prof. H. Obersteiner (Vienna). Brain 1884: 7; 289–309 (Translated from the original manuscript by C.E. Beevor, MD).

Alastair Compston
DOI: http://dx.doi.org/10.1093/brain/awm287 3057-3059 First published online: 30 November 2007

Writing in the 1880s, advances in microscopy and the preservation and staining of tissue made over the previous decade have enabled the fine structure and elements of animal and human tissue to be described in health …‘but also revealed an increasing number of changes, which denote the impress of a pathological condition’. Sceptics have challenged the status of certain so-called pathological features arguing that these may be variations of normal structure, non-specific alterations that accompany ageing or other ‘physiological’ processes, or artefacts of tissue handling. Indeed, in his previous work on the cerebral vasculature—motivated by the consideration that ‘the nervous elements, and especially the ganglion cells, are more sensitive than any other tissues to disturbances of their normal nutrition’—Professor Obersteiner (Fig. 1) has ‘frequently found that the occurrence of vessels considered to be diseased, [has] afterwards been found present, and never absent, in every healthy brain … such a false explanation brings in its train a series of false conclusions, and often in consideration of very great importance’.

Fig. 1

Professor Heinrich Obersteiner (1847–1922).

His studies are of fresh cerebral vessels, minimally prepared—no more than four days, ideally less, immersion of brain or spinal cord blocks in a solution of bichromate of potash. This allows the intact vessels to be separated from the macerated parenchyma and—after staining with carmine, picrocarmine, haematoxylin or aniline dyes (but not glycerine or oil of cloves)—examined in water or very weak salt solution, sealed with damar-lac at the edges of the coverslip, for up to 10 years. Only rarely is it necessary to harden the vessel prior to sectioning for examination of certain pathological conditions.

Normal arterial vessels consist of four coats (Fig. 2). The endothelium provides a single layer of flattened cells with oval nuclei orientated along the direction of blood flow …‘nearly always at the edge of the cell-nucleus is seen a strongly refracting bright granule, which projects into the nucleus itself, and the meaning of which is not yet explained. One refinement is that Th[omas] Deecke (The structure of vessels of the nervous centres in health, and their changes in disease. American Journal of Insanity, 1881: 37; 273–284) has observed within the endothelial layer, an additional component of cylindrical cells but these disappear as the smaller branches penetrate the brain parenchyma. The membrane fenestra is acellular and, under high powered microscopy, shows ‘bright spots (?holes) …’. This feature also disappears as the calibre of the arterioles reduces. The tunica muscularis wraps the inner layers and consists of cells with their nuclei arranged at right angles to those of the intima, the arrangement being for these muscle-fibres to become shorter and wider as the lumen diminishes. There is space between this and the over-lying adventitia to which is attached an array of pigment granules, fat-globules and fat-granule cells. This gap constitutes the Virchow–Robin space(s). But whereas Professor Obersteiner has failed to observe the additional ‘tendon-like membrane’ as part of the tunica muscularis, previously described by Deecke, each is agreed on the presence of structures that Deecke calls ‘separate large bundles of elastic fibres’ between the muscular coat and the adventitia but which … ‘I … have described … as folds … of the adventitia … [but] confess that I have frequently entertained doubts as to the accuracy of my view, without … being able entirely to accept that of Deecke’. Nor is Professor Obersteiner entirely confident of his position on the nature of stiff, long drawn-out processes, dissolved by the process of maceration, that project from the adventitia deep into the brain substance. More certain is that another fluid-filled gap exists between the adventitia and parenchyma that communicates with all other cavities in the brain and may contain numerous lymphoid corpuscles …‘but whether they are, as Deecke thinks, only wandering white blood-corpuscles, is not easy to decide’. For Professor Obersteiner, cerebral veins differ from arteries in that they consist only of the endothelium, middle muscular coat and adventitia (again, his views are not shared by Deecke); and capillaries are made only from the continuation of the arterial and venous endothelium and the surrounding adventitia.

Fig. 2

(A).A small artery of the brain, torn in such a manner that the individual layers are visible. a. Endothelial membrane. b. Fenestrated membrane. c. Muscular coat. d. Adventitial lymph-sheath. e. Little collections of pigment. (B) A normal artery, with fat granule cells in the adventitia; these form in patches a perfect ring round the lateral twigs. (C). An artery in which the muscular coat is perfectly calcified; at the lower end of the chief branch the calcified tube becomes fractured. (D). An artery from the brain of a patient who died from general paralysis of the insane; we see, scattered about, little enlargements caused by the paralysis of the muscular coat. (E). An artery from the neighbourhood of an apoplectic focus; the intima has fatty-atheromatous degeneration, while the muscular and adventitial coats are intact.

By studying the brains of neonates and children, Professor Obersteiner has shown that the fat granule cells that may surround the venous adventitia convey material for development of the medullated sheath. They reappear to take up matter exposed by ‘morbid dissolution of the medullated fibres’ …‘the flow of lymph is not sufficient to tear them away, and so they remain like “stranded-waifs” … . when development of the medullated fibres [is] completed … these fat-granule cells are found in the adventitia of the cerebral veins in the new-born condition as well as in old age, and are seen in variable quantities after deaths from different causes (even after sudden and most violent death) … [so that] the collection of fat on the adventitia of the cerebral veins, even when very abundant, is usually not to be considered a pathological occurrence’. Except perhaps in infants, pigment is invariably present in the adventitia of arteries and veins from individuals of all ages although its colour and staining properties may alter. For Obersteiner, it is derived from the waifs and stray fat globule cells marooned after myelination. Neither this type of pigment nor that present in meningeal tissue are ever the signatures of a pathological process. Conversely, haematoidin pigment accumulated within fat-granule cells, especially when present in large quantities, indicates ‘an exsudation [sic] of blood’: intra-vascular black pigment that may occlude the vessel and permeate into the walls of the vessels as seen in malaria; but the spinal cord pigmentation described by Dr Erlitzky is without doubt artefactual. Not to be mistaken, for a strictly pathological change is the deposition of calcareous material (releasing bubbles of carbonic acid after reaction with sulphuric acid and leaving crystals of calcium sulphate) that is found especially in the muscular coat. This may be so extensive as to decorate the entire capillary network with fragile calcareous tubes. That said …‘calcification of the muscular coat may impair the nutrition of the brain and, owing to the brittle condition of the vessels, lead to damage that is now pathological’.

In other contexts, the muscular layer is infiltrated by small point-like fat granules and these vessels share many features with those that are calcified …‘this degeneration of the muscular coat we must also consider as a process which leads to serious functional impairment … [and] we cannot … attach great pathological meaning to this fatty change of the muscular coat’. Over-growth of connective tissue from the muscular layer of the vessel, eventually impinging on and occluding the lumen …‘seem to me … can usually be referred to the peculiar conditions of the blood-pressure which prevails at those places not where the vessel divides dichotomously … but … where the smallest vessels branch off immediately from relatively large trunks … especially in the highest layers of the cerebral cortex … [and] in a more marked degree in the vessels of old age … [but] it appears wonderful that a process by which individual regions … robbed of their nutritive arteries can be referred to a normal occurrence, and produce no known disturbance’. Clearly, in other situations this nutritional deprivation through the blocking of vessels—which Deecke calls ‘callous degeneration … at the border of physiological and pathological conditions’—is not so trivial. Generously, since they are seen in healthy brains, Professor Obersteiner regards focal ballooning out of the adventitia ‘like a blown-out bag’ with surrounding fat-granule cells and pigment granules as normal unless these are giant or numerous. More difficult is the distinction between normality and a pathological state when these aneurysmal dilations are associated with accumulation of red blood corpuscles in the adventitial lymph space. Is this due to physiological diapedesis or rupture of the inner coats of the vessel? And Professor Obersteiner merges this thought with the formulation that discrete collections of fluid as cysts result from blockage to the passage of brain lymph-fluid that normally flows around the adventitial coat. Such a mechanism is the basis for the ‘état criblé’ although this is ‘chiefly confined to the white substance whilst cyst-formations … are only found in grey matter’.

On the issue of changes that are unambiguously pathological, atheromatous degeneration of the intima is indicated by spots made up of a granulated amorphous mass with numerous fat-granules, that easily detach to become fixed at a distal and more narrow part of the vessel; and these are especially prominent where there has been cerebral haemorrhage …‘[although] we can find this degeneration of the intima without cerebral haemor-rhage … this proves nothing against my view … that a great many of these cerebral haemorrhages can be referred to this morbid change in the vessels, and especially that these atheromatous masses are torn from the intima to form emboli in the smaller branches … I should therefore like to define fatty-atheromatous degeneration in the intima as one of the most serious diseases of the smaller brain-vessels’. In general paralysis, Professor Obersteiner finds variations in the calibre of vessels with a succession of irregular but not excessive dilations and constrictions that he attributes to vaso-motor denervation causing paralysis or loss of muscle tone in the tunica muscularis. In some cases, there is such an accumulation of lymph-corpuscles—‘improperly called “nuclei-growths” … [but] to be referred to an emigration of white blood-corpuscles’ that the muscular coat is scarcely recognisable. This is to be seen in different hyperaemic and inflammatory conditions and in general paralysis, sometimes with a formless substance colouring with carmine that seems to represent ‘the coagulation product of a transudation proceeding from the blood’. These are pathological changes that differ quantitatively from those seen normally, whereas the cells that accumulate around blood vessels in examples of meningitis, tuberculosis, sarcoma, cancer and syphilis are never normal—the lymph tracts acting as a convenient conduit for the dissemination of these cells.

Professor Obersteiner identifies processes that affect the normal structure of cerebral blood vessels in the ageing population but may translate into a morbid state. Since these do not invariably alter the nutrition of the brain parenchyma, it is somewhat unpredictable whether these processes do indeed escape the attention of the affected individual altogether, or lead to neurological symptoms and signs. That same unpredictability of how the cerebral vasculature may behave is still apparent in the account by Anne Ducros and colleagues, of the ‘string of beads’ disorder of reversible cerebral vasoconstriction, sometimes complicated by brain haemorrhage or infarction, resulting, in the 21st century, not from general paralysis of the insane but, rather, through the legacy of a different form of recreation—voluntary ingestion or inhalation of vasoactive substances (page 3091).

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