Stroke MARCH-APRIL 1984
A Journal of Cerebral Circulation VOL. 15 NO. 2
Editorial
The Pathogenesis of Watershed Infarcts in the Brain
ANSGAR TORVIK,
WATERSHED INFARCTS are ischemic lesions
which are situated along the border zones between the
territories of two major arteries, for example the anteri-
or and middle or the middle and posterior cerebral
arteries (fig. 1). They may also be located between the
territories of the major cerebellar arteries and they have
even been described between the territories of the
small arteries in the basal ganglia.17 However, the ex-
act nature of the latter lesions is more uncertain. The
infarcts may be pale or hemorrhagic or mixed but gen-
erally the hemorrhagic component is not prominent.
Altogether, approximately 10% of all brain infarcts
are watershed lesions.6 Similar infarcts are also found
in other organs, such as the heart and the kidneys, but
they are more easily recognized in the brain because of
the well defined course and extent of the cerebral
arteries.
The mechanisms whereby watershed infarcts devel-
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op have been debated for many years and they have
been variously ascribed to cerebral thromboangiitis
obliterans,7 12 episodes of systemic hypoten-
sion,1 •'• "• l7 carotid occlusions4-5 " and to microembo-
lism.6- '3-16 It has now been convincingly shown that
both hypotension and microembolism may cause such
lesions. However, in some cases, particularly in those
with a progressive or stepwise clinical course, the
mechanism still remains uncertain.
Watershed Infarcts Caused by Hypotension
A sharp drop in the systemic blood pressure is the
most frequent cause of watershed infarcts.1-3 "•17 Ap-
parently, the reduction in the blood flow becomes most
severe in the terminal areas of the vascular fields.
However, this is not the whole explanation because
unpredictable combinations of partial uni-and bilateral
infarcts may occur. The most striking and most fre-
quent location is the territory between the fields of the
anterior and middle cerebral arteries. Sometimes there
may be a diffuse nerve cell loss in the cortex in addition
to the localized infarcts but the hippocampus appears
to be remarkably resistent.1
The watershed infarcts caused by hypotension are
From the Division of Neuropathology, Department of Pathology,
Ulleval Hospital, Oslo 1, Norway
Address correspondence to: Dr. Ansgar Torvik, Section of Neuro-
pathology, Department of Pathology, Ulleval Hospital, Oslo I,
Norway.
Received April 13, 1983; revision 1 accepted August 13, 1983.
221
M.D.
rarely grossly hemorrhagic. This is somewhat unex-
pected, since the circulation obviously becomes re-
established after the initial ischemic damage to the
vascular endothelium. It is also remarkable, and of
relevance to certain findings discussed below, that the
small leptomeningeal vessels overlying the infarcts
rarely become occluded by secondary thrombosis.1-16
Watershed Infarcts Caused by Microemboli
It has often been speculated that the platelet aggre-
gates which so frequently block the small leptomenin-
geal arteries over watershed infarcts are microemboli
and thus the cause of the infarcts rather than secondary
events. However, secondary thrombi formed in situ
may have a similar appearance and it has therefore
been difficult to distinguish between emboli and
thrombi in this location.
It has now been shown in a considerable number of
cases that showers of cholesterol crystals or of tumor
emboli can block the vessels in these areas and cause
watershed infarcts. 2 - 8 1 0 ' 6 Although admittedly rare
causes, these examples of unusual embolic material
prove beyond doubt that particles of a certain size may
lodge preferentially in the watershed areas and cause
infarcts in the underlying brain. Generally, emboli
tend to pass as far distally as their size permits along
the superficial vascular tree, and they rarely follow the
sharp angles of the branches passing to the deeper sites
of the brain. Presumably, the microemboli to the wa-
tershed areas are extreme examples of this general
rule.
Watershed Infarcts Caused by Carotid Occlusions
It has been known for many years that thrombi at the
bifurcation of the carotid artery in the neck may cause
watershed infarcts between the territories of the anteri-
or and the middle cerebral arteries, and more rarely,
between the middle and posterior cerebral arteries.
Frequently, these cases present clinically with either
transitory ischemic attacks or a stepwise type of devel-
opment, or with evenly increasing clinical symp-
toms."- 15 Several authors have also commented upon
the frequent occurrence of platelet aggregates in the
overlying leptomeningeal vessels. 5 " 1 3
The watershed infarcts in carotid occlusions have
mostly been considered to be due to a reduced blood
flow analogous to the situation following systemic hy-
potension and the occluded leptomeningeal vessels a
 222
FIGURE 1. Hatched areas show the most frequent locations of
watershed infarcts in the brain.
result of "stagnation thrombi. "4-5- " Alternatively, the
vascular occlusions could be caused by microemboli
from the carotid thrombi before the lumen becomes
completely occluded. The observation that microem-
boli may lodge preferentially in the watershed aeas and
that "stagnation thrombi" are rarely found in infarcts
caused by hypotension, may support the latter sugges-
tion. J0rgensen and Torvik6 presented evidence that
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microembolization is a frequent phenomenon during
the build-up of cerebral thrombi in general, and mi-
croembolization to the watershed areas in carotid
thrombosis may be an example of this principle. Alto-
gether, these considerations suggest that the watershed
infarcts in carotid thrombosis are caused by microem-
bolization from mural thrombi rather than by "hemo-
dynamic disturbances".
Watershed Infarcts of Unknown Cause
In this group of infarcts there are neither episodes of
hypotension nor sources of microemboli which can
explain the lesions. Clinically, these cases often show
a stepwise or gradually increasing course.6- "• '4 The
lesions are composed of multiple small and partly con-
fluent bilateral infarcts which are most prominent in
the areas between the anterior and middle cerebral
arteries. The infarcts frequently give the cortex an ap-
pearance of "granular atrophy". 7
Many leptomeningeal arteries over the infarcts are
occluded by a material which shows all transitional
stages from recent platelet aggregates to completely
organized fibrous occlusions."- l4 These observations
thus indicate an ongoing process within the watershed
zones.
As mentioned above, such cases were originally
interpreted as instances of cerebral thromboangiitis ob-
literans. 7 - l2 This interpretation was convincingly refut-
ed many years ago by Fisher5 and later the infarcts have
been mostly considered due to a combination of re-
duced cardiac output and stenosing cerebral athroscle-
STROKE VOL 15, No 2, MARCH-APRIL 1984
rosis." However, convincing anamnestic or other indi-
cations for a reduction in cardiac output have never
been given.
Some years ago several cases of bilateral watershed
infarcts were described which in addition to the lepto-
meningeal vascular occlusions also showed general-
ized small vessel occlusion throughout the body.14
None of them showed evidence of primary disease of
the vessel walls. In one of these cases the diagnosis
was made in vivo and the case was subjected to detailed
hematologic investigations. No defects in the coagula-
tion factors could be detected and the platelet counts
were normal but the half life of the platelets was re-
duced from a normal value of 4 to 1.5 days. This
indicates a very marked platelet consumption, presum-
ably through intravascular aggregation. Later, several
other cases of this nature have been observed (personal
unpublished observations). Whether the mechanism in
such cases should be called microembolism or stagna-
tion thrombosis is a matter of opinion. The main point
is that there seems to be a primary disorder of the
coagulation mechanisms rather than a disorder of the
general circulation or of the vessel wall. This may not
be the only cause of this type of progressive watershed
infarct, but it represents a mechanism which is separate
from those of hypotensive episodes or microemboli
from mural thrombi. It is important that many organs
are examined for possible small vessel occlusions in
such cases.
Conclusions
Watershed infarcts are unique ischemic lesions
which are situated along the border zones between the
territories of the major cerebral arteries. Altogether,
they constitute approximately 10% of all brain
infarcts.
They may be precipitated by several different
mechanisms but episodes of severe hypotension are the
most frequent cause. It is also clear that showers of
microemboli may lodge preferentially in these areas
and cause infarcts in the underlying brain. This is the
most likely explanation for the watershed infarcts in
cases of carotid thrombosis.
Finally, there are examples of bilateral progressive
watershed infarcts with small vessel occlusions, in
which both episodes of hypotension and sources of
microemboli are lacking. Clinically, these cases often
have a stepwise or evenly progressive course. There is
evidence that at least some of these cases are caused by
hematogenous disorders with abnormal platelet aggre-
gation resulting in clogging of the small vessels in the
watershed areas of the brain and in many other organs.
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