doi:10.1093/brain/awm287
Brain (2007), 130, 3057^3059
FROM THE ARCHIVES
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).
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’.
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.
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 ‘‘strandedwaifs’’ . . . . 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,
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3058
Brain (2007), 130, 3057^3059
From the Archives
Fig. 1 Professor Heinrich Obersteiner (1847^1922).
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
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.
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,
From the Archives
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 haemorrhage . . . 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 brainvessels’. In general paralysis, Professor Obersteiner finds
Brain (2007), 130, 3057^3059
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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).
Alastair Compston
Cambridge