Age and Cerebral Infarction: A

Postmortem Study of 77 Cases of

Cerebral Infarcts in the Middle
Cerebral Artery Territory
A. Yelnik, MD; C. Derouesne, MD; H. Cambon, MD; C. Duyckaerts, MD;
J-J. Hauw, MD

Abstract
Adverse effect of age on ischemic stroke short-term mortality was reported in some studies and attributed either to more
frequent extracerebral causes of death or to an increased seventy of ischemia in the aged brain. Relationship between age,
size of infarcts, and causes of death were studied in 77 consecutive patients who died from infarction in the middle cere-
bral artery territory. Area of infarcts was assessed by planimetry, and results were expressed as an index of infarcted area.
No significant relationship was found between age and the size of infarcts, the cause of death, or the interval from stroke
to death. These results do not support the hypothesis of an increased seventy of ischemia in the aged brain. (I Gerintr
Psyclzinty Neiirol 1993;6:200- 204);

A dvanced age is a well-known predictor of

stroke m~rbidity.'-~It is also commonly re-
garded as a factor of poor prognosis after ischemic
stroke for short-term long-term
m o r t a ~ i t y , ~ , ~ ,and
~ - ' ~functional r e ~ o v e r y . ' ~How-
ever, an adverse effect of age on the ischemic stroke
outcome was not found in other Pre-
sumed mechanisms of the adverse effect of age on
short-term mortality in ischemic stroke are (1) more
frequent extracerebral causes of death','0''6 or (2) an
increase in the seventy of cerebral ischemia in the
aged brain, as suggested by some experimental
studies.17 However, these mechanisms remain hy-
pothetical in humans because the influence of age.
has not been taken into account in the few studies
devoted to the mechanisms of death after cerebral
Received August 13, 1991. Received revised March 9, 1992.
Accepted for publication April 20, 1992.
From the Department of Neurology (Drs Yelnik, Derouesne,
and Cambon), and the Laboratory of Neuropathology Raymond
Escourolle (Drs Duyckaerts and Hauw), HBpital de la SalpCtriPre,
Paris, France.
Address correspondence to Professor C. Derouesne, Depart-
ment of Neurology no 3, HBpital de la SalpCtriPre, 47 Boulevard
de l'H8pita1, 75651 Pans Cedex 13, France.
The aim of the present study was to determine
the influence of age on the size of the cerebral infarc-
tion, the interval from stroke to death, and the
causes of death in a postmortem series of patients
who died from cerebral infarction. Given the hetero-
geneity of brain lesions in ischemic stroke, the study
was restricted to cerebral infarction in the middle ce-
rebral artery (MCA) territory, which accounts for
70% to 80% of ischemic strokes in clinical ~ t u d i e s . ~ , ~ ~
Subjects and Methods
The postmortem records of 625 patients who died in
two Departments of Neurology from a General Hos-
pital between October 1978 and February 1984 were
reviewed. In these two departments, exception to
postmortem examinations were due only to the re-
fusal of permission by families (autopsy rate was ap-
proximately 85%).eOf the 625 cases, 159 had
ischemic cerebrovascular disease and 107 (67.3%)
had cerebral infarction in the MCA territory. Medical
reports of these patients were reviewed, and death
was considered to be due to cerebral infarction in
the MCA territory, according to the clinical and
pathological data, in 79 cases. Two cases were ex-

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 Age and Cerebral Infarction

cluded because of incomplete clinical data. The re- TABLE 1

maining 77 cases underwent complete postmortem General Characteristics of the 77 Cases
examination and full examination of the arteries sup- Sex
plying blood to the brain using a previously de- Males 35 (45%)
scribed technique.=FZ4 Females 42 (55%)
Diabetes 15 (19%)
The causes of cerebral infarction were classified Hypertension 68 (88%)
according to clinicopathologic criteria defined in pre- Age, yr
vious The causes of death were estab- Mean +SD 74.4 +. 9.5
lished according to clinical and postmortem data, in Range 47-92
agreement with the criteria of Silver et a1.21

brains of the 77 patients. The mean number of in-

Neuropa tho 1ogic Examination farcts per patient was 1.9 k 1.23; range, 1 to 6.
Coronal sections of the brain were obtained after
formaldehyde fixation. The extent of infarcts was
assessed macroscopically and, in case of doubt,
in sections embedded in celloidin and stained with Age and Cerebral Infarcts
The mean age of the patients did not vary as a func-
hematoxylin-eosin. The area of infarction was
tion of the cause of infarcts (F(2,24) = 1.14; P = .33),
reported on a schematic drawing of eight sections
the part of the MCA territory involved (F(2,74) =
from the frontal lobe to the occipital pole. The
1.05; P = .35), or the number of infarcts (r = -.16;
measurement of the area of infarction was calculated
P = .2). The mean age of the patients did not differ
on each of these drawings by planimetry (using
according to the.presence or absence of extensive in-
a semiautomatic image analyzer, ASM Leitz). The
farcts (t(75) = 1.65; P = .lo). However, extensive in-
results were conventionally expressed as an index of
farcts were more frequent in people aged less than
infarcted area, which was the ratio of the measured
75 years (45%) than in people over 75 years old
infarcted area to the theoretical area of the
(20%) (x2 = 5.9; P = .05).
MCA territory drawn on the eight sections accord-
The mean age of the patients did not vary as a
ing to Escourolle and As the thickness of
function of the size of infarcts (Table 3). No correla-
each macroscopic section did not vary greatly, this
tion was found between age and index of infarcted
index was directly proportional to the volume of the
area (r = -.17; P = .1).
infarct. Area of infarction was measured separately
by two examiners (H.C. and A.Y.), who did not
know the age of the patients, in the first 20 cases.
TABLE 2
The variation coefficient between the two measures Characteristics of the Infarcts in the 77 Patients
was 12%. Extensive infarcts ,were defined as infarcts
involving more than the MCA territory. Infarcts N (70)
were considered multiple when various territories Cause
Atherosclerosis 28
were involved without continuity, whatever the age Embolism from cardiac 31
of the infarcts. source
Statistical analysis was made using bilateral un- Undetermined or rare 18
paired f-test and ANOVA for comparison between Part of the MCA territory
qualitative and quantitative variables in two or more involved
Superficial 28
groups, and Pearson moment correlation coefficient Deep 7
for comparison between two quantitative variables Superficial + deep 42
(Statview 11). Extensive infarcts 25
Size of infarcts
Small (IIA < 15%) 26
Medium (15% < IIA 32
Results < 60%)
Large (IIA > 60%) 19
IIA (% of the MCA
General Characteristics territory involved)
The general characteristics of the 77 cases are shown Mean +SD *
37.6 28.9
in Table 1. The characteristics of the infarcts are Range 2-100
shown in Table 2. There were 144 infarcts in the MCA = middle cerebral artery; IIA = index of infarcted area.

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TABLE 3
Age of Patients and Size of Infarcts*
Size
Small
Medium
Large
'F(2,74) = 2.52; P = not significant.
Age nnd Cause of Death
Cause of death could be ascertained in 59 (77%)of
77 cases (Table 4). Extracerebral causes of death
were: pneumonia, 8; pulmonary embolism, 5; myo-
cardial infarction, 3; heart failure, 2; visceral bleed-
ing (anticoagulant therapy), 2; septicemia, 1. Causes
of death were multiple in 14 patients.
The mean age of the patients did not vary ac-
cording to the cause of death (F(3,73) = 1.72; P =
17)
Age and Internal From Stroke to Death
Interval from stroke to death ranged from 2 to 210
days. Death occurred in the first 8 days in 20 cases
(26%), between the 9th and the 30th days in 30 cases
(39%), and beyond the 30th day in 27 cases (35%).
No correlation was found between age and the
interval from stroke to death (r = .09; P = -44).
Discussion
This postmortem study is, obviously, not represen-
tative of the global population of ischemic stroke pa-
tients: it includes only the most severe cases who
died in two neurologic departments of a general
hospital. However, pathologic studies are the most
appropriate to determine the mechanisms of death
and the influence of age on the size of cerebral in-
farcts.
The mean age of the patients was higher than in
some clinical series (the maximum frequency of
ischemic strokes was found between 60 and 69 years
in the Lausanne Registry; the median age of stroke
patients was 69 years in the Stroke Data Bank27)but
not in other studies (the mean age of stroke patients
TABLE 4
Age of Patients and Cause of Death
Cause of Death N Age, yr
Extracerebral 35
Transtentorial herniation 17
Stroke recurrence 7 69.5
Undetermined 18
202 Journal of Geriatric Psychiatry and Neurology / Vol. 6 / October-December 1993
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Yelnik et a1
was 75 years in the Chambers et a14 study and 73.1
years for the men and 76.8 years for the women in
Age, yr the study of Terent28). There were more women
77.8 & 8.9 than men in the population studied: the male pre-
72.3 2 10.7 ponderance in ischemic stroke incidence is com-
73.6 2 6.6 monly found in epidemiologic studies' and in some
clinical studies= but not in other^.^,^ The cause of
cerebral infarction varies greatly in the literature
depending on the selection of patients and the
diagnostic criteria used to classify them. The fre-
quency of atherosclerosis as a cause of cerebral
infarction in the present study was in the medium
range of the frequenc reported in the literature,
which varies from 6%' to 7270.5 The frequency of
cerebral embolism from a cardiac source was higher
in our study than in the clinical studies of the
literature (from 9C/o5 to 31%29)but close to that of
postmortem s t ~ d i e s . ~ ~ , *The
' * ~cause
,~ remained un-
determined in 24% of cases, an intermediate fre-
quency compared to the data reported in the
literature (O%= to 61.6%27of cases).
In the literature, age beyond 70 years was found
to be a risk factor for poor prognosis for short-term
mortality in some studies."' However, the main
predictive risk factor for mortality as well as for poor
functional recovery was the clinical severity of the
stroke, related to the size of infarct^.'^,'^,^^ Age was
found to be a n additional factor in some studies4 but
not in other^.'^,^^ An increase in the severity of cere-
bral ischemia in the aged brain has been hypothe-
sized to document an adverse effect of age on the
prognosis of stroke. Animal studies have suggested
that the consequences of ischemia are more severe
in the aged brain due to poor collateral circula-
or increased sensitivity to ischemia with ad-
vancing In humans, a decrease in cerebral
blood flow (CBF) and metabolism has been shown in
some studies, mainly in gray related to
the cellular loss associated with age. However, this
decrease in CBF and metabolism in healthy elderly
was not found in other studies.39p40On the other
hand, diffuse cerebrovascular disease is frequent in
aged people, particularly in stroke patients.41 Distur-
bances of autoregulation of CBF have also been de-
scribed in the aged.= All these factors could result in
an increase of the severity of the ischemic stroke due
to the presence of multiple infarcts or to a larger size
of the infarct.
The size of infarcts is difficult to assess either by
76.3 2 10.1 computed tomographic scan or at postmortem exam-
71.5 2 1.5 ination. Direct measurement of the volume of infarct
f 10.9 is not available. Quantitative assessment was made
75.2 2 9.4 by measurement of the limits of infarcts42 or, as in
 Age and Cerebral Infarction
the present study, by p1animet1-y~~ of the area in-
volved by the infarcts. The area of infarcts has to be
expressed as a ratio in order to discard individual
variations in the brain size. An index proportional to
volume of infarct, like the index of infarcted area
used in the present study, is obviously an approxi-
mation. However, the inaccuracy inherent to this
evaluation was not biased for age because the exam-
iners did not know the age of patients. Interobserver
reliability was fairly good, the discrepancy mainly
resulting from the difficulty in drawing the borders
of recent infarcts (less than 3 days). In the present,
study, no statistically significant relationship was
found between age, the size of infarcts in the MCA
territory, and the number of infarcts per patient.
Moreover, infarcts involving more than the MCA
territory were more frequent in people aged less
than 75 years than in older subjects. These results
do not support the hypothesis of an adverse effect of
age per se on cerebral ischemia.
The cause of death was sometimes difficult to as-
certain, because death could result from multiple
mechanisms, or remained undetermined. However,
it could'be determined in 77% of the cases, a per-
centage similar to that of previous pathologic stud-
ies.'8,21The cause of death and the time from stroke
to death are related mainly to the size of infarcts.
Newbil12' found the time from stroke to death to be
shorter in the aged, in relation to an increase in as-
sociated pathology. Giroud et all did not find a rela-
tionship between age and the 1st week mortality
rate, but they found an increase in mortality beyond
the 2nd week in people aged over 70 years. Sacco et
a132 did not find that .age was a risk factor for an
early recurrence of ischemic stroke. In the present
study, death was more frequently related to trans-
tentorial herniation in people under 75 years of age
and to extracerebral causes in people older than 75
years, in accordance with the results of Viitanen et
a1.16 This fact can be related to the higher frequency
of extensive infarcts in the younger group. How-
ever, no significant difference was found in the time
from stroke to death between the two groups. This
discrepancy can be interpreted as indirect evidence
for a higher short-term mortality of ischemic stroke
in the older people, due to extracerebral causes of
death.
Conclusion
No evidence was found, in this postmortem study,
that age had an adverse effect on the size of cerebral
infarction in the MCA territory in humans. Some
Journal of Geriatric Psychiatry a n d Neurology I Vol. 6 I October-December 1993
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data suggest that the increased short-term mortality
in ischemic stroke in the aged is related either to the
higher frequency or to the greater severity of extra-
neurologic causes of death.
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