1. health and fitness
2. disease

5vs
UM EÅ UNIVERSITY M EDICAL DISSERTATIONS
New series No 201 — ISSN 0346-6612
From the D epartments o f Geriatric Medicine, Internal Medicine,
and Physical Medicine and Rehabilitation,
University o f Umeå, Sweden
LONG-TERM EFFECTS OF STROKE
by
Matti Viitanen
Umeå 1987
LONG-TERMS EFFECTS OF STROKE
AKADEMISK AVHANDLING
som med vederbörligt tillstånd av Rektorsämbetet vid Umeå Universitet
för avläggande av doktorsexamen i medicinsk vetenskap kommer att
offentligen försvaras i föreläsningssal D, Tandläkarhögskolan, 9 tr,
Regionsjukhuset i Umeå, fredagen den 9. oktober kl 09.00
av
Matti Viitanen
Umeå 1987
LONG-TERM EFFECTS OF STROKE
Matti Viitanen, Departments of Geriatric Medicine, Internal Medicine and
Physical Medicine and Rehabilitation, University of Umeå, S-901 85
Umeå, Sweden
ABSTRACT
Stroke, which has an increasing incidence with age, causes an irreversible brain damage
which may lead to impairment, disability and decreased life satisfaction or death.
Risk factors for death, recurrent stroke and myocardial infarction, were analyzed in 409
stroke patients treated at the Stroke Unit, D epartm ent of M edicine, Umeå University
H ospital, between Jan. 1, 1978 and Dec. 31, 1982. The causes of death were related
with the tim e of survival. In fully co-operable (n=62) 4-6 year stroke survivors, the
occurrence of m otor and perceptual impairments, o f self-care (ADL) disability and of
self-reported decreased life satisfaction due to stroke was determined.
The probability of survival was 77% three months after stroke, 69% after one year, and
37% after five years. M ultivariate statistical analysis indicated that im pairm ent of
consciousness was the m ost im portant risk factor for death follow ed by age, previous
cardiac failure, diabetes mellitus, intracerebral hemorrhage and male sex. During the first
week, cerebrovascular disease (90%) was the m ost dom inant prim ary cause of death,
from the second to the fourth week pulm onary em bolism (30%), bronchopneum onia
during the second and third months and cardiac disease (37%) later than three months
after stroke. The risk of recurrence was 14% during the first year after stroke and the
accum ulated risk of stroke recurrence after 5 years was 37% after stroke. The estimated
probability of m yocardial infarction was 7% at one year and 19% at 5 years. High age
and a history o f cardiac failure increased the risk of recurrent stroke. The risk of
m yocardial infarction was associated with high age, angina pectoris and diabetes
mellitus. The highest risk of epilepsy was found between 6 and 12 months after stroke.
Motor im pairm ent prevailed in 36% of the long-term survivors, perceptual impairments
in up to 57% and decreased A D L-capacity in 32%. As regards ecological perception,
perceptual function variables were distinctly grouped into low and high level perception
which together with m otor function explained 71% o f the variance of self-care ADL.
While levels of global and of domain specific variables of life satisfaction appeared stable
in clinically healthy reference populations aged 60 and 80 years, the stroke had produced
a decrease in one or more aspects of life satisfaction for 61% of the long-term survivors.
Although significantly associated with m otor im pairm ents and ADL disability, these
changes could not only be attributed to physical problems.
Key words: stroke, cerebrovascular disease, prognosis, recurrent stroke, m yocardial
infarction, epilepsy, life satisfaction, m otor function, self-care ability, perception, causes
of death.
UMEÅ UNIVERSITY MEDICAL DISSERTATIONS
New series No 201 — ISSN 0346-6612
From the Departments of Geriatric Medicine, Internal Medicine,
and Physical Medicine and Rehabilitation,
University of Umeå, Sweden
LONG-TERM EFFECTS OF STROKE
by
Matti Viitanen
Umeå 1987
Copyright © 1987 by Matti Viitanen
ISBN 91-7174-312-X
Printed in Sweden by
the Printing Office of Umeå University
Umeå 1987
To Siri
and my Parents
CONTENTS
ABBREVIATIONS
6
ABSTRACT
7
ORIGINAL PAPERS (I-V)
8
INTRODUCTION
A. HISTORY OF CEREBROVASCULAR DISEASE
B. INCIDENCE OF CEREBROVASCULAR DISEASE
1.Global aspects
a. First stroke
b. Recurrent stroke
2. Swedish data
3. Changes in incidence
C. RISK FACTORS FOR CEREBROVASCULAR DISEASE
1. General aspects
2. Risk factors for recurrent stroke
3. Prevention of stroke
D. PREVALENCE OF CEREBROVASCULAR DISEASE
IMPAIRMENT, DISABILITY and LIFE SATISFACTION
1. General aspects
2. Impairments
a. Mobility
b. Perceptual function
c. Cerebral integration
d. Intrapsychological impairment
3. Disabilities
4. Life satisfaction
4
9
10
11
12
13
15
15
17
18
20
22
E.
F.
G.
MORTALITY AND PROGNOSIS AFTER
CEREBROVASCULAR DISEASE
1. General aspects
2. Changes
3. Risk factors for death
4. Causes of death
22
23
23
23
MORBIDITY AFTER CEREBROVASCULAR DISEASE
1. Myocardial infarction
24
2. Epilepsy
25
AIMS OF THE STUDY
PATIENTS AND METHODS
1. Background population
2. The Non-Intensive StrokeUnit
3. Patients
4. Definitions
5. Methods
6. Statistical methods
26
26
26
27
29
29
RESULTS
30
DISCUSSION
33
ACKNOWLEDGEMENTS
39
REFERENCES
40
PAPERS
I
II
III
IV
V
51
65
77
89
101
5
ABBREVIATIONS
ADL
ASA
CVD
ICIDH
SAH
TIA
activities of daily living
acetylsalicylic acid
cerebrovascular disease
International classification of impairments, disabilities, and
handicaps
subarachnoidal hemorrhage
transient ischemic attack
6
ABSTRACT
Stroke, which has an increasing incidence with age, causes an irreversible brain damage
which may lead to impairment, disability and decreased life satisfaction or death.
Risk factors for death, recurrent stroke and myocardial infarction, were analyzed in 409
stroke patients treated at the Stroke Unit, Department of Medicine, Umeå University
Hospital, between Jan. 1, 1978 and Dec. 31, 1982. The causes of death were related with
the time of survival. In fully co-operable (n=62) 4-6 year stroke survivors, the occurrence
of motor and perceptual impairments, of self-care (ADL) disability and of self-reported
decreased life satisfaction due to stroke was determined.
The probability of survival was 77% three months after stroke, 69% after one year, and
37% after five years. Multivariate statistical analysis indicated that impairment of
consciousness was the most important risk factor for death followed by age, previous
cardiac failure, diabetes mellitus, intracerebral hemorrhage and male sex. During the first
week, cerebrovascular disease (90%) was the most dominant primary cause of death, from
the second to the fourth week pulmonary embolism (30%), bronchopneumonia during the
second and third month and cardiac disease (37%) later than three months after stroke. The
risk of recurrence was 14% during the first year after stroke and the accumulated risk of
stroke recurrence after 5 years was 37%. The estimated probability of myocardial infarction
was 7% at one year and 19% at 5 years after stroke. High age and a history of cardiac
failure increased the risk of recurrent stroke. The risk of myocardial infarction was
associated with high age, angina pectoris and diabetes mellitus. The highest risk of epilepsy
was found between 6 and 12 months after stroke.
Motor impairment prevailed in 36% of the long-term survivors, perceptual impairments
in up to 57% and decreased ADL-capacity in 32%. As regards ecological perception,
perceptual function variables were distinctly grouped into low and high level perception
which together with motor function explained 71% of the variance of self-care ADL. While
levels of global and of domain specific variables of life satisfaction appeared stable in
clinically healthy reference populations aged 60 and 80 years, the stroke had produced a
decrease in one or more aspects of life satisfaction for 61% of the long-term survivors.
Although significantly associated with motor impairments and ADL disability, these changes
could not only be attributed to physical problems.
Key words: stroke, cerebrovascular disease, prognosis, recurrent stroke, myocardial
infarction, epilepsy, life satisfaction, motor function, self-care ability, perception, causes of
death.
7
ORIGINAL PAPERS
I.
Viitanen M, Eriksson S, Asplund K, Wester PO, Winblad B.
DETERMINANTS OF LONG-TERM MORTALITY AFTER
STROKE. Acta Med Scand 1987; 221: 349-56
II.
Viitanen M, Winblad B, Asplund K. AUTOPSY-VERIFIED CAUSES
OF DEATH AFTER STROKE. Acta Med Scand, in press.
III.
Viitanen M, Eriksson S, Asplund K. THE RISK OF RECURRENT
STROKE, MYOCARDIAL INFARCTION AND EPILEPSY DURING
LONG-TERM FOLLOW-UP AFTER STROKE. Submitted.
IV.
Bernspång B, Viitanen M, Eriksson S. IMPAIRMENTS OF
PERCEPTUAL AND MOTOR FUNCTIONS. THEIR INFLUENCE
ON SELF-CARE ABILITY 4-6 YEARS AFTER STROKE. Submitted.
V.
Viitanen M, Fugl-Meyer KS, Bernspång B, Fugl-Meyer AR. LIFE
SATISFACTION IN LONG-TERM SURVIVORS AFTER STROKE.
Scand J Rehab Med in press.
INTRODUCTION
A. HISTORY
In Nej Jing, the oldest preserved Chinese book of medicine (475-221 BC)
the risk of apoplexy was said to be greatest in the summer when the pulse was
as a stroke of a hammer and when the pulse was still stronger the disease
struck all at once1.
At about the same time apoplexy was described in the Hippocratic writings
(400 BC)2. The heating of the blood vessels of the head was thought to cause
the flow of black bile into the head or to attract phlegm, and aphasia was first
connected with right side hemiplegia.
A retaios3 (50 or 150 AD) described the brain lesion as being on the
opposite side of the trunk of the paralysis and also mentioned the possibility of
urinary retention or incontinence. He observed that the disease usually
affected the elderly who often died. The most important treatment in more
severe apoplexy was phlebotomy and the degree of phlebotomy should be
calculated exactly so as not to kill the patient. Phlebotomy could be repeated.
Soranus of Ephesus (A.D. 98-138) reported that "hemiplegic paralysis"
was common in old age, occurred seldom in youth and occurred most
frequently in the winter.
Gabriel Fallopius (1561) described the arterial circle of vessels at the base
of the human brain. In his illustration, however, there were no the posterior
communicating arteries. Casserio showed the complete union of the posterior
communicating arteries as early as the year 1616, but only on one side. Willis
(1664) described the circle of Willis and the intracerebral blood vessels and
also reported the clinical importance of the circle. He also observed that
damage in the region of the capsula intema could cause hemiplegia. Johan
Jacob Wepfer of Schaffhausen (1658) illustrated the siphon of the carotid
arteries and described the course of the middle cerebral artery. In a Treatise
on Apoplexy (1658), Wepfer described cerebral hemorrhage as a cause of
apoplexia and patients who recovered from hemiplegia within 24 hours. He
recognized that an obstruction between the cerebral arteries and jugular veins
could produce an apoplexy. He also described the signs of those at risk to
develop apoplexy: namely the obese whose face were livid and those whose
pulse were constantly irregular. Hypertensive individuals or subjects with
9
cardiac risk were said to run a greater risk of stroke. Francois Bayle (1677)
related cerebral sclerosis with apoplexy.
In the 18th century, van Swieten (1754) suggested that cerebral embolism
may cause apoplexy. William Heberden (1802) described transient cerebral
vascular insufficiency, which could precede paralysis. Serres (1822)
described a patient with cerebellar apoplexy and Parker (1845) reported
pontine apoplexy. Abercrombie (1828) tried to classify apoplexy into three
classes: primary apoplexy was described as intracerebral hemorrhage or
massive cerebral infarction, the second class was those with a sudden pain in
the head (most cases can be recognized as subarachnoid hemorrhage) and the
third class consisted of patients with sudden hemiplegia/paresis without
stupor, which may include patients with cerebral vascular insufficiency. As
late as the mid-19th century cerebral vascular occlusion was described as a
cause of cerebral softening and brain infarction. Henry Duret (1873)
demonstrated the areas of distribution for the anterior, middle and posterior
cérébral arteries and the penetrating branches to the basal ganglia and brain
stem. Gowers (1875) described a patient with mitral stenois who suffered
from blindness and contralateral hemiplegia. At autopsy, emboli were found
in the middle cerebral artery and in the central retinal artery. The origin of
the emboli was found in the auricular appendages.
Chiari (1906) pointed out the that main source of emboli in the elderly was
in the carotid bifurcation, (for reviews see4,5)
B. INCIDENCE OF CEREBROVASCULAR DISEASE
1. Global aspects
a. First stroke
In the National Survey of Stroke study in USA, 1971-1976, Kuller and co­
workers6 observed an annual incidence rate of initial stroke of 1.4/1000
population. In South Alabama, USA, 1980, the (hospitalization) incidence of
first stroke was 1.4/1000 population and the diagnostic distribution of the
events was 85% cerebral infarctions, intracerebral hemorrhages 8%,
subarachnoidal hemorrhage 6% and unspecified type 1% .
o
In a multicenter study, coordinated by the WHO , stroke was registered
between 1971 and 1974 in 17 centres. The highest incidence was in Akita,
10
Japan, 3.2/1000 of the whole population and 32.6/1000 population 75 years
and older. Four of these 17 centres were in Northern Europe. In Copenhagen,
the indicence rate was 2.6/1000 of the whole population and in the population
75 years and older 15.3/1000, in Espoo, Finland 1.5 and 28.1, respectively,
and in North Karelia, 2.0 and 18.2. In Sivenius's study in Kuopio, Finland9,
the incidence of stroke was 2.4 for the whole population and for 75 years and
older 23.5.
b.
Recurrent stroke
O
In the WHO epidemiological multicenter study , recurrent stroke was
found in 14% of the patients under 65 years and in 18% over that age. There
was no difference between the sexes nor between the European centres. In an
n
epidemiological study in Alabama , 13% of all strokes were recurrent and,
26% in the National Survey of Stroke study111 and in Oxfordshire, Great
Britain11, 24% were recurrent.
In a group of hospitalized stroke patients, in Stockholm12, a history of
previous stroke was reported in 19% and in Söderhamn13, in 17%, and in
Umeå, 30% had had a previous stroke14.
In follow-up studies, in Framingham, USA, Sacco and co-workers15
reported a 42% five-year cumulative recurrence rate in men and a 24% rate
in women, and in Beijing, China Chen and Ling16 found a cumulative
recurrence rate in cerebral thrombosis after one year of 13%, after two years
19% and after three years 33%, and in cerebral hemorrhage 5%, 10% and
10% respectively. Sivenius and co-workers9 (1985) had a recurrence rate of 6
% during the first year after stroke in Kuopio, Finland, and Ahlsiö and co­
workers17 found recurrency in 23% after two years in Stockholm.
2. Swedish data
A Swedish study of the incidence of hospital admissions caused by stroke in
1o
Uppsala (1964), gave a rate of 2.3 admissions /1000 population . Ten years
later in the same catchment area 0.4/1000 inhabitants under the age of 70 were
admitted to hospital due to first stroke19. In Gothenburg, patients 15-65 years
of age were registered from 1971 to 1974 and the crude annual incidence was
o
0.5 per 1000 population in men and 0.3 in women and in both sexes 0.4 . The
overall incidence of stroke in Söderhamn, 1975-1978, was 2.9/1000 and the
11
mean age for both sexes was 73 years; men 71 years and women 75 years, and
1'l
the incidence of stroke increased by 55% per 5-year interval of age . In an
epidemiological study in Lund20, in 1983 and 1984, the crude and age
adjusted incidence of first stroke was 1.7/1000 population and for all strokes
2.0. The incidence for the age groups 65-74 years was 6.0, 75-84 years 13.6,
and over 85 years 18.9 per 1000 population. In nothern Sweden stroke
incidence was 3.9/1000 in age group 55-64 years and 9.8/1000 in the
population aged 65-74 years21.
3. Changes in incidence
22
In the population of Rochester, Minnesota, Matsumoto and co-workers
observed a decreased average annual incidence rate between the groups
studied from 1945 through 1954 and from 1955 through 1969, and Garraway
22
and co-workers
found a decreasing incidence of cerebral infarctions
between the populations studied from 1945 to 49 and from 1970 to 74. This
decrease occurred, in both sexes and in the higher age groups.
In Hisayama, Japan, a trend towards a decreasing incidence of stroke was
observed by Ueda and co-workers24. The 5-year incidence of intracerebral
hemorrhage in men decreased and the same trend was observed also in
cerebral infarctions in both sexes24.
Kotila 25 compared the incidence of stroke in Espoo and Kauniainen,
Finland, between 1972-73 and 1978-80 and found a declining trend in the ageadjusted incidence of stroke. The largest, statistically significant decline was
observed in the incidence of cerebral hemorrhage in men and subarachnoid
hemorrhage in women. The incidence of cerebral infarction was unchanged.
In a study in Stockholm, based on data obtained from the Swedish Cause of
Death Register and the Inpatient Care Register, Alfredsson and co-workers
found a decreasing trend in the age-adjusted incidence of first stroke in
women. In men, the incidence of all strokes increased roughly by 1.8%
annually and this increase was observed both in first and in recurrent strokes.
In Gothenburg, stroke incidence decreased in women aged 15-65 years
between 1971 and 1981 but in men it remained unchanged27.
12
C. RISK FACTORS FOR CEREBROVASCULAR DISEASE
1. General aspects
The incidence of stroke is strongly related with age and the rate more than
7 o g 9 9
o
doubles per decade after 55 years ’ ’ ’ . For example, in Copenhagen in the
age groups 55-64, 65-74 and over 75, the incidences were 2.7, 5.7 and 15.3
per 1000 population respectively.
Male sex is overrepresented especially in atherothrombotic brain
infarctions21,28.
Race has proved to be as a risk factor. Blacks had higher age-specific
incidence rates than whites in South-Alabama and Maoris than non-Maoris in
New Zealand 29. in studies from Japan, Japanese 8’ 311 had a higher incidence
than Europeans but the stroke incidence rate of Hawaiian Japanese men
71
appeared to be similar to that of occidentals .
Familial factors are reported to be a risk factor by Diaz and c o - w o r k e r s 3 2 ,
and the living relatives of the stroke or the TIA patient had multiple stroke
risk factors (as for example hypertension, heart disease) and may therefore
run a greater risk of stroke than the relatives of the patients' spouses.
Diabetes mellitus is a risk factor for atherothrombotic brain infarction and
77
the risk is higher in women than men . The risk is strongly correlated with
hypertension, but according to Abbot and c o - w o r k e r s 3 4 , diabetes mellitus is
an independent risk factor for thromboembolic stroke. Weinberger and co35
workers observed in their study of 102 consecutive patients with peripheral
artery disease that patients with diabetes mellitus had higher risk of stroke and
were more prone to irreversible destruction of ischemic brain tissue than
non-diabetics, regardless of the nature of the circulatory disturbance.
o zr
The Framingham data showed that stroke risk is strongly related to the
elevation of blood pressure. Hypertension was the dominant predisposing
factor for stroke. It was highly relatedn/rboth
to atherothrombotic brain
77
infarction and intracerebral hemorrhage ’ . Patients v/ith hypertension
were prone to develop cardiac impairments, such as cardiac enlargement,
which can be seen on X-ray and atrial fibrillation and ECG abnormalities.
These changes are far more frequently observed in patients with CVD .
The risk of developing stroke from all diagnoses is threefold in patients
with coronary heart disease. Congestive cardiac failure increases the general
risk for atherothrombotic brain infarction, in which there is a 9-fold increase
13
OQ
in stroke incidence .
In Tilburg, the Netherlands40 myocardial infarction and cardiac
arrhythmias were found to be significant risk factors for stroke, and the
relative risk was greater among young persons in the study. Atrial fibrillation
is correlated especially with embolic brain infarctions15,41.
Previous transient ischemic attack (TLA) had a significant excess risk of
stroke compared with controls in Rochester, Minnesota42 and the
Netherlands40. Muuronen and Kaste43 found a 4.8% risk of brain infarction
in patients with TLA during the follow-up time. The risk of stroke is shown to
increase among TLA patients, if other stroke risk factors were also present44.
Bonita and co-workers45 observed a 3-fold increase of the risk of stroke
for smokers compared with non-smokers and this association remained
significant after adjusting for hypertension. Herman and co-workers40
reported that smoking was not associated with stroke.
Hillbom and Kaste46 reported, in a consecutive series of 100 15-55-yearold patients with ischemic brain infarction, that for 40% ethanol intoxication
preceeded the symptoms and out of them twenty patients were still intoxicated
at the time of admission. The frequency of ethanol intoxication preceding
stroke was 4-7 times higher in males and 6-15 times higher in women than
that of an age and sex related Finnish population. The ethanol-induced risk of
stroke was highest in middle-aged women and young men. Occasional and
heavy drinking increased the risk of stroke. In contrast, in the Honolulu Heart
Program there was no significant correlation between alcohol consumption
and thromboembolic cerebral infarction. Compared with non-drinkers, the
risk of hemorrhagic strokes was doubled in light drinkers (1-406 g/month)
and almost trippled in heavy drinkers (>1160 g/month) and was independent
of hypertensive status or other risk factors47. No association between alcohol
and stroke has been found in some other studies40 for a review see 4^.
Obesity has been shown to be a risk factor in many studies511,40(for a
review see49) which may be related to hypertension and diabetes mellitus.
Elevated blood cholesterol and lipids were risk factors in younger patients
in The Framingham studie50 and in middle-aged men in Finland51,52.
Low physical activity during leisure time was reported by Herman and co­
workers40 as a significant risk factor and in a multivariate regression analysis
it was shown that persons with regular non-strenuous activity had a greater
relative risk compared with individuals with regular strenuous activity. It is
also reported that low physical activity at work was associated with an
14
increased risk of stroke53.
Dyken and co-workers49 considered geographic location, season, climate,
socioeconomic factors, and oral contraceptive use to be less well-documented
risk factors.
2.
Risk factors for recurrent stroke
There have been few studies concerning recurrent stroke and the number
of patients included has been rather small. Consequently, the information of
risk factors for recurrent stroke are limited. It also is preferable to use a
multivariate analysis for large materials in order to estimate the independent
importance of other risk factors. The decreasing incidence also may make the
pattem of risk factors change with time.
Hypertension, the most important risk factor for stroke, increases the risk
of recurrency. Diastolic blood pressure was shown to be a risk of subsequent
stroke in patients with one or more TIAs54, and antihypertensive therapy
reduced the incidence of fatal and non-fatal stroke recurrency55,56,57.
M arquardsen58 showed in his study an increased risk of recurrence in
younger survivors, patients with previous stroke and patients with motor
deficits. In 1983 Sacco and co-workers15 reported from the Framingham
study that recurrent stroke was common after atherothrombotic brain
infarction and it was usually of the same type as the previous stroke. It did not
depend on age, but on the presence of cardiac comorbidity prior to initial
stroke and hypertension. The influence of these factors was greater in men,
who had a five-year cumulative recurrence rate of 42%, than in women, who
had only a 24% recurrence rate.
Previous stroke multiplies the risk of recurrent stroke compared with that
of the first stroke59 and is shown to be a risk factor for cerebral infarctions
ca
and all strokes .
3.
Prevention o f stroke
Miettinen and c o - w o r k e r s ^ O reported from a Finnish multifactorial
primary prevention trial in which vascular diseases, hyperlipidemias,
hypertension, smoking, obesity and abnormal glucose tolerance were treated
in a high risk test group, a considerably improved risk factor status and a
reduced incidence of stroke in middle-aged men. A similar intervention trial
15
was performed in the USA6i but did not diminish stroke mortality more than
in the control group which may be an effect of the fact that the risk factors of
the control group diminished.
The positive effect of hypertension treatment on stroke mortality and
morbidity is well-documented62,63,64,65’66’67. The decrease in mortality
varied from 34 to 93% and the morbidity (fatal and non-fatal stroke)
decreaseed by 34-74%. In the North Karelian study68, mortality from stroke
decreased in men between the periods from 1971 to 1972, 1977 to 1978 and
1980 to 1981 and in women between the first two periods and, thereafter, it
increased, which may depend on relaxed hypertension control. In the
reference area, the trend of decreasing mortality was observed between
cohorts. Hypertension treatment in patients over 60 reduced the rate of fatal
stroke by 30% compared with the rate of the control group69. The rate of all
strokes was reduced by 58% compared with the rate of the control g r o u p 7 0 .
There is no solid scientific background yet for the reasons why
prophylactic acute and long-term treatment with anticoagulants is given to
71 72
patients with TIA and atrial fibrillation ’ . Acetylsalicylic acid treatment of
TIA patients may have some effect on carotis-TIA patients and on patients
with several TIAs72,73,74.
D. PREVALENCE OF CEREBROVASCULAR DISEASE
The overall prevalence rate of cerebrovascular disease in England and
Wales, in a study carried out between 1955 and 1956, was found to be
4.9/1000 population (men 4.5 and women 5.2) . In Rochester, Minnesota ,
1970, the prevalence was 6.1/1000 population and in the age group 65-74
years 4% had had a stroke and for 75-year-olds and older this figure was 8%.
In the National Survey of Stroke study in the USA116, the prevalence was
estimated to be 7.9/1000 population for all ages.
Petlund (1970) found, in the county of Aust-Agder in Norway, that the
point prevalence rate for stroke was 4.4/1000 population (4.0 men and 4.8
women)77. In a Finnish population study, 1973-197678, the age-adjusted
prevalence of stroke was 10.3/1000 in men and 5.8/1000 in women. The
highest prevalence was found in men old 65-74 years (38.6/1000) and in
women over 75 years of age (32.4/1000). In Copenhagen, Denmark, 1976,
the prevalence was 6.5/1000 in men and 3.9/1000 in women79.
16
IMPAIRMENT, DISABILITY AND LIFE SATISFACTION
AFTER STROKE
1. General aspects
A normative model of the consequences of stroke is given in the
International Classification of Impairments, Disabilities, ancl Handicaps
(ICIDH)80:
ETIOLOGY -> PATHOLOGY -> MANIFESTATION/DISEASE -»
IMPAIRMENT -> DISABILITY -» HANDICAP
According to the ICIDH the person who evaluates the impairments,
disabilities and handicaps classifies them all normatively. The def tiitions are:
IMPAIRMENT is a loss or abnormality of psychological, physiological -)r anatomical
structure or function. Impairments reflect disturbances on the organ level.
DISABILITY is a restriction or lack (resulting from impairment) of the ab: 1ity to perform
an activity in the manner or within the range considered normal for a 1 uman being.
Disabilities reflect disturbances on a personal level.
HANDICAP is a disadvantage for a given individual, resulting from mpairment or
disability. The six dimensions of handicaps represent the socialization of impairments or
disabilities.
HEALTH «
FU NCTION
Spontaneous/
Treatm ent
*
IMPAIRMENT
t
REHABILITATION
A BILITY
4
I
SA T IS F A C T IO N
D ISA B IL IT Y
D ISSATISFA CTION
17
Fugl-Meyer and Fugl-Meyer81 have described a model where the end point
is not normative.
According to them, common impairments after brain damage are:
Mobility:
motor function
joint function/pain
Sensing:
exteroception
proprioception
perception
Cerebral integration:
cognition
communication (aphasia)
motor praxis (apraxia)
Intrapsychological (such as depression, stigmatization)
Several authors have attemped to analyze the predictive value of different
impairments in the early stage for the final functional outcome after stroke
(for review see 82). There is a positive correlation between the degree of
impairment on admission and on discharge. High age implies here a negative
correlation. Whereas many factors may play important roles as early
predictors of the late outcome after stroke, there appears, however, to be no
valid mathematical model for the reasonably powerful early prognostication
0 9 CQ
of functional recovery ’ . Early rehabilititative measures, such as physioand occupational therapy, may, though, shorten the length of stay in the acute
wards84 and improve the functional recovery85.
In this dissertation the functions/impairments focused on were motor
control, perception, cognition and depression. Ability/disability was
measured in terms of daily self-care proficiency while life satisfaction was
recorded by means of self-reports.
2. Impairments
a. Mobility
11
Classically, the major sign .of stroke is hemiparesis/plegia. Petlund
reported a prevalence of hemiplegia/hemiparesis in 39% of stroke survivors
in Norway, and Sprensen and co-workers 79 in 44% in Denmark.
In the long-term follow-up by Marquardsen 58 , 63.6% of the men and
18
67.7% of the women had residual hemiplegia one year after stroke, after 5
years 57.4% and 63.5% and after ten years 61.5% and 56.4%. Kotila and co­
workers86 found hemiparesis in the acute stage in 73% of the patients, after
three months in 50% and after one year in 37% of the one-year survivors.
b. Perception
Perception is most frequently studied in terms of neglect and hemiinattention. The anatomical correlation of this symptom is localized much
more frequently to the inferior parietal lobe of the right hemisphere than to
the frontal lesions87. Neglect occurs also with lesions confined to subcortical
grey structures, such as the basal ganglia and the thalamus and, sometimes,
with cortical frontal lobe damage.
Patients with left-sided hem iplegia showed less spontaneous
improvement88 and less social adjustment58 than patients with a right-sided
motor impairment. Moreover, Denes and co-workers8^ reported a lower
degree of improved self-care ability and in motor function and more frequent
and severe unilateral spatial neglect in left than in right-sided hemiplegic
patients. Kinsella and F o r d ^ O found that four out of seven (57%) patients had
remaining hemi-inattention 18 months after stroke and these seven patients
were more dependent on total ADL than patients without this symptom in the
acute phase. Hier and co-workers^l reported that 9 weeks was the median
duration for the recovery of left hemisphere neglect. In a study of 72 patients
with minor stroke or TIA92, a worse performance was found in Rey's figurecopying test in patients with the former than the latter or in controls. This
indicate that perceptual impairment is not correlated to hemiplegia and that it
is important to investigate all stroke patients.
c. Cerebral integration
In Petlund's study77 25% of the patients with hemiplegia/-paresis had
cognitive impairment. In Copenhagen, Denmark, there was a prevalence of
79
impaired memory in 56% of the stroke patients .
Cognitive impairment has been found to prevail in 22% of men and 31 % of
women one year after stroke, after five years 34%/36% and after ten years
CO
15%/36% . Cognitive impairment in stroke patients, measured with MiniMental State test, has been shown to be influenced negatively by depression,
19
lesion volume93 and age94. Frontal lobe ischemia was correlated with
disorientation as to time and space, and left mid-temporal ischemia was
correlated with memory disturbances and dyscalculia95. Kotila and coozr
workers , using a battery of neuropsychological tests, found cognitive
impairments in 39% of one-year stroke survivors under 65 years of age.
d. lntrapsychological impairments
Poor psychosocial adjustment with depression, anxiety and fear of relapse
has been observed after a stroke as has also irritability and inability to control
anger96,97. Robinson and Price98 reported a depression prevalence of 22% 34 years after stroke and of 27% after 5-6 years. In comparison, about 15% of
the elderly who lived at home were found to suffer from depression99. Brain
damage in the left frontal lobe was closely associated with depression up to
one year after s t r o k e 1 " . The depression correlated significantly with selfcare disability up to two years, peaking at six months. Depression may
interact with disability and impair recovery.
Denial is a common defence against the psychologically critical impact of a
stroke94,101,102. Whereas denial in the acute phase may be psychosocially
adaptive, persistent denial or minimization of impairments can be detrimental
to the long-term social adaption after stroke1113. In the long run, however,
focussed illness behavior with regressive dependency appears to be the most
common intrapsychological problem among stroke patients, and, in addition,
feelings of being stigmatized are common104. Some 50% of hemiplegic
patients admitted to the Department of Rehabilitation Medicine, Umeå,
reported symptoms of stigmatization throughout their first year after
stroke103.
3. Disabilities
The ability to manage the simple tasks of daily self-care is a major concern
for the stroke patient. Other important aspects of ability/disability are
occupation, leisure and sexuality. Hence, disabilities must be seen in relation
to the goals the patient had before and can set up after stroke. Ability to
manage self-care is, however, a basic survival goal, and the capacity to do so
has been widely measured in studies of the outcome of stroke treatment (for a
comprehensive review see103)
20
The point prevalence of self-care disabled men after stroke in Aust-Agder
county in Norway, 1965, was 2.4/1000 population and for women 3.7/1000
and for the whole population 2.7/1000 77.
Kotila and co-workers found that 68% of the one-year stroke survivors
were ADL-independent. Garraway and co-workers106 made a comparison
between a stroke rehabilitation unit and medical units in a follow-up of a
controlled trial of stroke patients who were independent prestroke, not
unconscious on admission and who could not walk without aid or had
hémiplegia. When discharged from hospital, 58% of the patients from the
stroke unit and 37% from the medical units were independent. After one year
the corresponding figures were 55 and 57%.
o/r
In the Espoo-Kauniainen study , 69% of patients who survived one year
had returned home within 3 months and 78% within 12 months. In
1O
Söderhamn about 10% of stroke patients were hospitalized after one year,
and in Umeå the corresponding figure was 16% (patients treated at general
medical wards) . The positive effect of stroke units on outcome has been
shown in many studies107,108,109 and in Umeå only 7% of patients with
cerebrovascular disease need nursing-home care after one year 84 .
77
Petlund
found disability caused by stroke alone in 42% of stroke
survivors, and caused by stroke together with other disabling disease in an
o
additional 21%. Aho and co-workers reported that, after one year, 62%
were independent as regards self-care while 9 % were totally dependent on
17
other people. Ahlsiö and co-workers found that about 75% were ADLindependent two years after stroke. Andrews and co-workers110 showed that
there was no difference in self-care ability between younger and elderly
stroke patients during the first year after stroke, but the latter were more
often institutionalized than the younger with similar functional level of
recovery. Severe ADL disability was found in 28% of patients over 65 years
old one year after stroke.
"Time is what I have" is a remark often made by long-term stroke
survivors. In agreement with other authors, Fugl-Meyer and co-workers111
reported that the majority of subjects who suffered a first stroke in their
vocationally active years never returned to work. In Northern Sweden almost
90% of younger patients with hemiparesis/-plegia do not take up to their
premorbid leisure activities again to the full11^; while Trudel and co­
w o rk e rs 113 showed a loss of leisure activities in 37.5% of carotid
endarterectomy survivors. Labi and co-workers114 reported a decrease in
O /T
21
socialization outside their homes for 51 % of physically restored long-term
stroke survivors, and within the their homes for 36%, and a decreased social
activity involving hobbies/interests for 46% of the women and 29% of the
men.
4. Life satisfaction
Some objective indicators of a good quality of life are health, sufficient
funds, absence of psychological distress, and availability of a supportive
family and friends115.
Measurements of quality of life have became increasingly popular during
the last quarter of a century. Many different approaches and theoretical
models have been proposed (for general overviews see116,117). The latter
authors117 equated quality of life with life satisfaction. They also categorize
quality of life/life satisfaction into one general "global" and several domain
specific areas. There are only a few studies of life satisfaction among the posti rn found that younger first stroke subjects with
stroke population. Sjögren
hemiplegia/paresis to a great extent reported decreases in domain specific
satisfaction regarding leisure (approximately 80%) and sexual life (67% in
males and 42% in females). The decreases closely paralleled decreased
activity in these areas. Ahlsiö and co-workers 17, found that, in a consecutive
sample of stroke patients, global life satisfaction had decreased for 77% of
patients.
D. MORTALITY AND PROGNOSIS AFTER CEREBROVASCULAR
DISEASE
1. General aspects
In the National Survey of Stroke Study1^ in the USA, the mortality rate
was 48% after one year and 70% after five years. The mortality rate among
patients aged 65-74 years was similar (41% after one year and 6 6 % after 5
years) to that of all patients but the age group 75-84 years (54% after one year
and 78% after 5 years) had an approximately 25% higher mortality rate and
patients over 85 years (72% after one year and 93% after 5 years) about 50%
higher mortality after one year and after five years. In Söderhamn , 34% of
patients had died during the first three months after stroke and about 70%
22
9 fx
after four years. Mortality from stroke in Stockholm was, for men 60-69
years 9 /1000 population and, for women of the same age, 5.2/1000. In the age
groups 70-79 and 80 years and older, the mortality rate for men was 22 and
54/1000 and for women 20 and 43/1000.
2. Changes
Stroke mortality has declined by 76% over thirty years in Rochester,
Minnesota, and the primary cause, according to Whisnant119, is that the
incidence of stroke has decreased. A decline is reported from other parts of
the USA120,121, Australia122, Taiwan123 and Europe124,125.
In Norway, mortality statistics have shown a steady decline in stroke
m ortality12^, except for patients with intracerebral infarction and over 70
years old. In Stockholm, the mortality from stroke decreased annually by
2.3% in men and 3.5% in women from 1974 to 198126.
3. Risk factors fo r death
Many studies8,13,58,124,127,128,129 have reported that the most important
prognostic factor for death is impairment of consciousness has been in the
acute phase. Other clinical symptoms, related to the neurologic damage and
127 128
reported as prognostic indicators, are degree of hemiplegia ’ , pupillary
abnormalities, paralysis of conjugate ocular movement, bilateral extensor
CO
plantar response and respiratory abnormalities .
Long-term prognosis is also affected by age58,122,127,128,129,130 earuer
tzo i o n i o i
ioi
hypertension
cardiac failure , atrial fibrillation and myocardial
ion
121
120182
infarction
and male sex
. Diabetes mellitus
’
and peripheral
120
vascular disease
have been reported as negative prognostic factors for late
127
124
survival. On the other hand, Abu-Zeid and co-workers
, Kotila
and
19 0
Howard and co-workers
could not show any signicant effect of diabetes
mellitus, hypertension, hypertensive cardiac disease, myocardial infarction
and atrial fibrillation on survival.
4. Causes of death
Paper II reports the causes of death from different studies. In the acute
phase, cerebrovascular disease is the main cause of death (31-59%). In
23
follow-up studies, cerebrovascular disease was found as the cause of death in
23-48% and cardiac diseases in 18-39% of the cases. Bronchopneumonia
varied as the cause of death from 9-34%. Pulmonary embolism was found at
autopsy and varied from 0-18% as cause of death.
Ueda and co-workers24 found in their epidemiological study, in which the
autopsy rate was 8 8 %, that the underlying cause of death in patients with the
initial clinical diagnoses of cerebral infarctions was 54% cerebral infarction,
5% cerebral hemorrhage and 41% other causes. In cerebral hemorrhages the
cause of death was 8 8 % cerebral disease per se. Autopsy-verified causes of
death in the study a b o v e l 3 2 were cerebrovascular disease 2 3 % , malignancy
25%, respiratory tract infection 17%, myocardial infarction 4% and other
causes 31%.
E. MORBIDITY AFTER CEREBROVASCULAR DISEASE
1. Myocardial infarction
Increased heart-type creatine phospho-kinase isoenzyme (CK-MB) values
have been reported in acute stroke133-134. Norris and co-workers 135
demonstrated increased CK-MB iso-enzyme in 11 % of acute stroke patients
and these patients also showed more evidence of acute myocardial ischemia on
their ECG. Arrhythmias often occur in acute s t r o k e 1 3 6 ’ 1 37, From autopsy
studies, focal myocardial damage is reported more often in patients with
intracranial lesions. This leads to rapid increase in intracranial pressure
which, it is postulated, increases the levels of plasma catecholamines13^, von
Arbin and co-workers 1311 found enzyme curves suggestive of acute
myocardial infarction in 6 % of patients with acute cerebral infarction but
only in 1% of hospitalized controls. Signs of myocardial infarctions of
various ages were found in 79% at autopsy. Of these, 11 % happened just prior
to stroke, 15% were concomitant with the stroke and 7% occurred
immediately post-stroke. In 16% of patients without clinically suspect
myocardial infarction,, myocardial infarction was found at autopsy. Coronary
artery disease was frequently found in patients with TIA or minor stroke140.
In studies of the natural history of stroke from the 1960's, the risk of
myocardial infarction was 1.8-3.0% annually141*142. M a r q u a r d s e n 5 ^
reported 37 myocardial infarctions in 362 discharged patients (10.2%).
Leonberg and Elliot143 in a preventative study of 88 survivors after the first
24
cerebral infarction found, in a mean follow-up period of five years, five fatal
and two non-fatal myocardial infarctions (8 %). In the Swedish Cooperative
Study of A S A 144, 4 4 of 505 selected patients (8.7%) with cerebral infarction
suffered a myocardial infarction during a two-year follow-up. Other
therapeutic trials reported a rate of 1.5-3% annually145>146.
2. Epilepsy
Shinton and co-workers147 showed that stroke patients had a prior epilepsy
prevalence of 45/1000 compared with 6/1000 in that of matched controls.
In an autopsy study, Richardson and D o d g e 1 4 8 found epilepsy in 5.8% of
patients with cerebral hemorrhage and in 1.3% of the controls. Convulsive
seizures occurred in 28% of patients with cortical lesions. In Marquardsen's
study 58( 23 out of 404 patients had epileptic seizures, none of them had a pre­
stroke history of epilepsy. Typical Jacksonian seizures were not noted and the
focal convulsion occurred on the affected side in 9/23 patients and grand mal
seizures were found in 12 patients. Pirttimäki and c o - w o r k e r s 149 reported a
9% incidence of epilepsy in stroke patients. Electroencephalographic
examination showed that 14 out of 29 (48%) patients had no signs of irritative
activity. Autopsies showed one or more cerebral infarctions in the cortex in
11 patients, only one subcortical infarction was found. In a prospective study,
73 patients under 75 years of age with ischemic stroke were followed up by
Rosenkvist and Skyhpj O l s e n 1 50 2-4 years after the stroke and they found an
epilepsy rate of 1 1 %.
G. AIMS OF THE PRESENT STUDY
The aims of the present study were to:
- estimate the long-term survival of CVD patients and to weigh risk factors
that could have effects on survival
- describe the causes of death after stroke
- estimate the risks of recurrent stroke, myocardial infarction and epilepsy
during the long-term follow-up and to weigh the risk factors which have an
influence on recurrent stroke and myocardial infarction
- describe the occurrence of motor and perceptual impairment on self-care
ability in communicable 4-6 year stroke survivors and to analyze the effects
of motor impairment and self-care disability on life satisfaction
25
PATIENTS and METHODS
Methods and procedures are described in detail in each article (I-V) and are
summarized here.
1 . Background population
(I-V)
9
Umeå University Hospital has a catchment area of 9409 km with a
population of 116 000 (49.6% men). Seventy percent live in the city of Umeå
and have a lower average age than the inhabitants in the surrounding rural
area.
Acute stroke patients from the catchment area are admitted to the
Department of Medicine (250-325 patients/year). Patients with subarachnoid
hemorrhage are admitted to the Department of Neurosurgery and have been
excluded from this presentation.
Patients with intracerebral hemorrhage, non-embolic cerebral infarction,
embolic cerebral infarction and TIA were included in the present thesis as
"stroke" patients.
2. The Non-Intensive Stroke Unit at the Department o f Medicine,
University Hospital, Umeå, Sweden
Patients from the catchment area of Umeå University Hospital, regardless
of age, who, with no preceeding trauma to the head, present focal
neurological dysfunction of a duration not exceeding one week or patients
with TIA during the last week, are admitted to the Stroke Unit if there is a bed
available.
The stroke unit is a 6 -bed, non-intensive care and research unit for patients
who meet the admisson criteria, and has been described in detail in previous
publications15 1>152,153
patjents have been shown to be representative
of all those patients admitted to hospital for acute stroke within this district84.
3. Patients
1.
In articles I, II and III, all patients with a well-defined CVD-diagnosis
who were treated in the Stroke Unit at the Department of Medicine, between
Jan. 1st 1978 and Dec. 31st 1982, a total of 409 patients with specific stroke
diagnosis, were included out of the 428 patients with acute cerebrovascular
26
disease. The 19 patients excluded did not fulfill the diagnostic criteria (see
definition below). In studies I and II, patients were followed up to June 30,
1984 or to death, and, in study III, 3.5-7 years after stroke or to death. All
patients were accounted for.
2.
In articles IV and V, all 120 4-6 year survivors from the patients who
had been treated at the Stroke Unit between Jan. 1st 1978 and Sept. 30th 1981
were initially included. After the exclusion of unwilling or noncommunicable subjects, 75 and 62 remained to be investigated in IV and V
(patients with TIA excluded), respectively. Sixty subjects (26 subjects aged
78-81 years and 34 subjects 60-61 years) who had not been hospitalized
during the last 7 years and were clinically healthy were taken as the reference
group for life satisfaction variables.
4. Definitions
^.Definition fo r previous disease (I-III)
Previous stroke - acute CVD in medical history and treated in hospital.
Previous TIA - acute focal neurological deficits of vascular origin lasting
less than 24 hours in the medical history.
H ypertension - a history of high blood pressure, treated with
antihypertensive agents.
Cardiac failure - typical symptoms of this disease treated with digitalis or
diuretics.
Atrial fibrillation - a history of irregular cardiac rhythm, verified by
electrocardiogram.
Angina pectoris - exertion-correlated substemal or left-sided chest pain,
disappearing within ten minutes upon rest or upon taking nitroglycerin.
Myocardial infarction - a hospital report of myocardial infarction.
Diabetes mellitus - diagnosed by a physician or newly detected during
hospital stay for stroke (not based on elevated glucose levels in the early
phase).
b.Criteria for clinical diagnoses in the Stroke Unit (I-V)
Intracerebral hemorrhage - signs of an intracerebral hemorrhage on
27
computerized tomography (CT scan), a hemorrhagic pattem in spinal fluid
analysis or hemorrhage found at autopsy.
Non-embolic cerebral infarction - focal neurological deficits persisting
more than 24 hours with no signs of a hemorrhage on CT scan or on analysis
of spinal fluid analysis or verified infarction; no potential source of emboli at
autopsy.
Embolic cerebral infarction - diagnostic criteria as for non-embolic
infarction but with a potential source of embolus (atrial fibrillation or a
recent acute myocardial infarction with mural thrombosis found at autopsy,
rheumatic valvular disorder, endocarditis, mitral valve prolapse and/or
previous history of systemic embolisation) and sudden onset of symptoms.
Transient ischemic attack (TIA) - focal neurological deficits of presumed
vascular origin and of less than 24 hours' duration.
c. Clinical and. autopsy criteria for causes of death (II)
CVD - Clinical picture of CVD with decreasing consciousness. Autopsy
findings confirming CVD with large hemispheric involvement, brain stem
infarction or hemorrhage, and signs of brain edema with uncal herniation.
Cardiac disease - Clinical evidence of cardiac failure, myocardial
infarction and severe pulmonary edema. Autopsy findings of pulmonary
edema supported by evidence of underlying significant heart disease.
Bronchopneumonia - Clinical picture of pneumonia with fever and autopsy
findings of confluent bronchopneumonia involving at least the major part of
one lobe.
Pulmonary embolism - Clinical picture of pulmonary embolism confirmed
by arterial blood gas determination, chest X-ray, pulmonary scintigraphy or
pulmonary-artery angiography. Saddle pulmonary embolus or bilateral
multiple pulmonary emboli at autopsy.
Other causes - Other diseases that lead to death and cases where neither
clinical picture, nor laboratory, radiological or autopsy findings gave an
apparent cause of death.
d. Criteria fo r events after stroke (III)
Recurrent stroke - When the WHO definition of stroke was fulfilled and
occurred more than one week after the index eventi54.
28
Myocardial infarction - Defined by WHO criteria155.
Epilepsy - When paroxysmal and transitory seizures developed suddenly,
ceased spontaneously and showed a tendency to recur, this led to drug
treatment156.
5. Methods
Motor function was assessed in articles IV-V using a stroke specific test,
developed by Fugl-Meyer and co-workers157, based on the motor
deveplopment concepts described by Twitchell15^. The test is valid and has
been found to be valid and r e l i a b l e Perceptual function was evaluated
in paper IV using a tool which is a modification of that developed at the
Loewenstein Rehabilitation Hospital, Raanana, Israel161. Cognition as an
aspect of cerebral integration was assessed using the test developed by Folstein
and co-workers 162 (Mini Mental State). Occurrence of depression was
screened using the method decribed by Montgomery and Åsberg163. Self-care
ability (self-care ADL) was measured using a stroke specific method164, by
which twenty items within the sphere of hygiene, dressing and feeding were
assessed. Life satisfaction was gauged through structural interviews using the
subjects' self-reported global (one item) and domain specific (6 items)
satisfaction prior to the stroke (retrospect) and at the time of the investigation.
Thus changes could be computed.
6 . Statistical methods
The Mantel-Haenszel life table technique 165 was used to estimate the
proportion of survivors and instances of recurrent stroke, myocardial
infarction and epilepsy (I-III). Relative risks between subgroups of patients
were calculated using the log rank test(I). Multivariate analysis was
performed with BMDP's program for regression on life table curves with
Cox's proportional hazard model166 (I, III) in order to analyze the relative
importance of clinical variables for the risk. Factor analysis calculations were
based on a matrix of Pearson's correlation coefficients (IV). Simple cross­
tabulations (% 2 -test) were used for testing differences between proportions
(II, V).
29
RESULTS
Survival and. risk factors for death after stroke (I)
The survival rate of the 409 patients with cerebrovascular disease was 77%
after 3 months, 69% after one year, 52% after three years and 37% after five
years. An excess mortality rate among patients was seen during the first six
months after stroke the prognosis, thereafter, being relatively good.
The most important prognostic factor for death was impairment of
consciousness on admission, with a standard coefficient of 8.09 (p<0.001),
while the second most important factor was age, 5.94 (p<0.001). History of
previous cardiac failure and diabetes mellitus worsened the prognosis.
Previous TLA indicated a reduced risk of death. Other earlier diseases had no
effect on outcome. The prognosis for men was worse than for women. The
only CVD diagnosis which was a risk factor for death was intracerebral
hemorrhage.
Autopsy findings after stroke (II)
The accumulated probability of death during the first three months after
stroke was 23% and, thereafter, 7-10% annually. In the first week after the
stroke, death was ascribed directly to the cerebrovascular accident in 90% of
patients. From the second to fourth weeks, pulmonary embolism was the most
common cause of death, bronchopneumonia in the 2 -to-3 -month interval and
cardiac disease thereafter. There were no significant differences in the cause
of death between men and women nor between age groups <75 and >75years
within the first three months, although the older group appeared to die more
often from bronchopneumonia.
As expected, for the majority (76%) of patients with intracerebral
hemorrhage the cause of death was their cerebral disease. In 55 % of patients
with non-embolic cerebral infarction the cause of death was non-cerebral; the
corresponding proportion was 64% in embolic cerebral infarctions.
A potential source of emboli was found at 18 of the 82 autopsies performed
in patients who died within 3 months of having a stroke, and, of them, 15 were
in the heart.
The causes of death in the 128 patients who died later than three months
30
after stroke during the follow-up period were cerebrovascular events 27%,
cardiac disorder 32%, bronchopneumonia 18%, pulmonary embolism 5%
and other/uncertain causes 18%.
Of 12 patients who died of pulmonary embolism, four had been capable of
walking without assistance.
Recurrent strokes, myocardial infarction and epilepsy after stroke (HI)
During the follow-up, recurrent stroke occurred in 93 patients The risk of
recurrent stroke was highest during the first year after admission and
thereafter remained fairly constant (5-8% annually). High age and congestive
heart failure were predictors of increased risks of recurrent stroke. A history
of previous stroke (before inclusion in this study) did not achieve statistical
significance but may be a possible risk factor. Previous TIA, hypertension,
myocardial infarction, angina pectoris, atrial fibrillation and diabetes mellitus
(for definition see Methods) and male sex were of less importance for
recurrent stroke.
Fifty-seven patients developed myocardial infarction, the greatest
estimated proportion occurring during the first two months after stroke. High
age, diabetes mellitus and angina pectoris were associated with significantly
increased risks. The other factors (see above) did not increase the risk of
myocardial infarction.
Only 15 out of the 347 patients who survived more than one month
developed epileptic seizures. The greatest risk of onset of epilepsy appeared to
be between 6 and 12 months after stroke.
Impairment and disability in long-term stroke survivors (IV)
The factor analysis grouped motor and perceptual functions into three
distinct groups. One of these represented motor function only, which was
impaired in 36% of long-term survivors. The perceptual items fell into the
two remaining groups. Applying the principles of ecological perception
167,168^ one of these characterized low level perception. Deficits within this
level of perception prevailed in 8 %. The other factor adequately
characterized high-level perception which was impaired in 57%. Finally, selfcare disability (in terms of dependency) prevailed in 32%. The joint effect of
the three impairments (one motor and two perceptual) factors on self-care
31
ability was analyzed using a multiple linear regression model. With this
model, 71% of the variance in self-care ADL capacity could be explained.
Life satisfaction 4-6 years after stroke (V)
Decreased general and/or domain specific satisfaction with life was found
in 61% of the 62 communicable patients with completed stroke. Twelve
subjects (15%) experienced a decrease in four or more out of the 7 aspects and
14 (18%) had decreased life satisfaction in only one aspect. Most often,
subjects felt a decrease in global life satisfaction (42%) followed by
diminished satisfaction with sexual life (38%) for the 42 married subjects.
Reduced satisfaction in leisure and self care ADL was found in about one third
of interviewees.
Subjects with motor impairment had significantly more frequently changes
in global, leisure and sexual satisfaction than individuals with normal motor
function. Decreased global satisfaction, self care ADL-satisfaction and sexual
satisfaction were found significantly more often in subjects with ADLdisability. However, a fair proportion of unimpaired patients reported
negative changes in life satisfaction.
No statistical differences in life satisfaction were found between the two age
groups of reference subjects. Life satisfaction level prior to stroke in the
patients did not differ significantly for any items from those of the reference
group. But after stroke, satisfaction with life in general, self-care ADL,
leisure and sexual life were significantly lower for the patients than for the
reference subjects.
32
DISCUSSION
In this thesis, a sample of a stroke population was analyzed and followed up.
The sample could be regarded as representative of the total hospitalized stroke
popoulation except that patients with subarachnoidal hemorrhage were
excluded.
The patients in nursing homes and at the Department of Geriatric Medicine
were not generally admitted to the Department of Medicine and therefore
some events of stroke were missed in patients with several risk factors for
stroke and death (high age, cardiac failure and diabetes mellitus). Some
patients with TIA and minor stroke may be assumed to receive treatment at
home, especially in rural areas. It can be assumed that these groups are so
small that they would not influence the results as Terent13 showed that 90% of
Swedish patients suffering from stroke turned to their hospital for care.
In the present study, age was a risk factor for death (I), as was also
recurrent stroke and myocardial infarction (III). In the population study H-70
in Gothenburg, Sweden, Svanborg and c o - w o r k e r s 1^ demonstrated that the
more recent cohort was more healthy and had fewer diseases. This may mean
that biological age represents a group of factors that is genetically linked but
can be affected by external factors such as eating habits, smoking, alcohol and
leisure activities. This can result in the mean age of stroke patients increasing
in subsequent cohorts.
The impairment of consciousness was the most important risk factor for
death in the acute stage after stroke. As shown in study II and by Ulbrich 1711
and Bounds and co-workers171, for most patients who died during the first
week after stroke cerebral disease was the primary cause of death, indicating
that the brain damage per se, its dimension and/or localisation is the
determinant that causes the poor outcome.
Hypertension per se was neither a risk factor for death (I) nor for
myocardial infarction after stroke (III). The risk of recurrent stroke
increased in hypertensives with embolic cerebral infarction (III). High
systolic blood pressure has been shown to be significantly associated with
stroke mortality in patients aged 65-84 years172. In studies made in the
1960's, hypertension increased the risk of d e a t h 1 7 3 >1 7 4 and recurrent
stroke 175 but in studies in the 1970-80's no significance was found for
hypertension as a risk factor for death after s t r o k e 8 >12 4 ,1 2 7 ,1 2 8 . Thjs may be
the effect of hypertension treatment which has changed the patterns of risk
33
factors. In the study by Solzi and co-workers130 all patients treated at a
Rehabilitation Center, from 1958 to 1977, were recorded and hypertension
was found to be a risk factor for death. However, no division was made
between patients observed in different decades.
Cardiac failure was a risk factor for recurrent stroke (III) and for death
(I). In earlier times, cardiac failure was often caused by hypertension and
arteriosclerosis but today it is most frequently a sequel to coronary artery
d i s e a s e 1 7 6 . Sacco and co-workers130 found that risk of death or recurrent
stroke was influenced by male sex, cardiac comorbidity and hypertension. It
may be possible with new medical therapies to further reduce the effect of
hypertension on arteriosclerosis and cardiac failure and also to improve the
treatment of cardiac failure and so reduce the negative effect of this risk
factor.
The risk of myocardial infarction was highest in the first weeks after stroke
(III), which may indicate that cerebral damage can cause myocardial
damage138 by increasing the level of plasma catecholamines.
Cardiac diseases caused death in 32% of patients up to three months after
stroke (II) and sim ilar results are reported in several other
s t u d i e s 1 2 8 » ^ , 175,177. xhe accumulated risk of myocardial infarction was 7%
one year and 19% five years after stroke (III). It has been shown in selected
stroke patients144 that there are about 1% annually "silent" myocardial
infarctions of lesser clinical importance. Such patients may have been missed
in the present study because electrocardiograms were not taken during the
follow-up. As expected in patients of high a g e 1 7 8 , 1 7 ^ 4 0 % of those with
post-stroke myocardial infarctions in our study died (III). Prevention of
major cardiac events by using betablockers may be a possible way to improve
the late prognosis, as shown in subarachnoidal hemorrhages180 and also in a
recent study in stroke patients181. High dose acetylsalicylic acid had no
preventive effect on myocardial infarction in patients with cerebral
infarction144.
Our patients were followed up and conventional therapy was applied to
attain good secondary prevention. Comparisons between earlier and recent
studies are difficult to make as the distribution of CVD diagnoses has changed
and mortality decreased. The risk of recurrent strokes was 14% after one
year and 38% after five years (III). In previous studies, the recurrence rate
was reported to be 8-13% in the natural history of cerebrovascular disorder
(for review see58). Chen and L i n g 1 6, in a recent study reported a cumulative
34
recurrence rate after cerebral thrombosis at one year of 13% and after 3
years 33%. These results are similar to those found in the present study.
Recurrent strokes are a further risk of death in a later phase. Miah and co­
workers128 reported that, in 17% of unselected patients, recurrent stroke was
the underlying cause of death during a three year follow-up and in the
Swedish Cooperative Study of ASA 144 recurrent stroke caused death in 25%
of selected patients during a two-year follow-up. No differences were found
between the ASA and placebo groups regarding recurrent stroke.
Diabetes mellitus was a risk factor for death (I) and myocardial infarction
after stroke but not for recurrent stroke (III). Several other studies have
shown poor outcome for diabetic stroke patients 6 8>130>182 anci aiso for
patients with hyperglycaemia183 or abnormal H bA ic184,18^ and other studies
have shown no effect on the outcome124-127. In the Framingham study,
diabetes mellitus and glucose intolerance constituted greater risks of
myocardial infarction than of stroke186. After myocardial infarction, the
patients with diabetes mellitus had a poorer outcome than the control
population187. Stroke causes myocardial damage 138 and the hearts of
diabetics may be more vulnerable due to general arteriosclerosis. Another
explanation may be that patients with hyperglycemia in stroke develop more
pronounced cerebral edema188, and hyperglycemia was shown to decrease the
regional cerebral blood flow189. It was also demonstrated that incomplete
cerebral ischemia may be more harmful than complete. This could be
explained by the high levels of lactic acidosis which is in turn due to on the
level of blood glucose190.
In our study, previous TIA (see definition under methods) constituted
neither a risk of recurrent stroke nor a risk factor for myocardial infarction
(III) and, surprisingly, previous TIA indicated a reduced risk of death in this
stroke population (I), which may be an effect of the small population or that
all patients with TIA in the present study were treated with acetylsalicyclic
acid. Other studies124»129 confirm that TIA is not a risk factor for death and
that patients without other risk factors for death had the same survival rate as
the age-matched population. On the other hand TIA patients who had 3 or
more risk factors for death, had a greatly reduced survival rate. Patients with
multiple TIA had a significantly greater risk of TIA recurrence and stroke or
death than patients with single TIA72. Young and middle aged TIA patients
had no stroke during the 55 months follow-up191. In earlier studies (for
review see ref192) the major cause of death in TIA patients was myocardial
35
infarction . Asymptomatic coronary artery disease was found in 28% of 83
consecutive patients with TIA compared with 6 % for controls195. it is
suggested therefore that TIA may be a marker of asymptomatic coronary
artery disease195. An active investigation of coronary heart disease should be
performed in TIA patients in order to plan optimal comprehensive
management.
After the first week, complications of stroke were the primary causes of
death both in study II and other studies170 -17 1. Pulmonary embolism is
difficult to diagnose because of its varying symptomatology194. That is why a
prophylactic low-heparin regime may reduce the occurrence of venous
thromboembolic events, which are common after stroke, as demonstrated by
the fibrinogen uptake test by Prasad et co-workers195 and Mellbring and co­
workers196. The first study showed that pneumatic compression of the calf in
elderly hémiplégies (mean age 78 years) had no positive effect. However, it is
possible that prophylactic treatment with anticoagulants197 and an intensified
clinical observation could be of great importance here.
Of the 347 patients (85% of the whole population studied) who survived
more than one month (III), 15 (4%) developed epileptic seizures during the
follow-up. The risk factors could not be calculated because of the small
number of patients with epilepsy. The highest risk was from 6 to 12 months
after stroke and this interval was confirmed by Skyhpj Olsen 198 . He found
epilepsy in 33% of patients with cortical infarcts and that only one out of 33
patients with subcortical infarcts developed epilepsy. These findings were also
verified by Hornig and co-workers199 who also found the localization of the
lesion in the brain area supplied by the medial cerebral artery. Lesser and co­
workers 200 did not accept that the initial reduction of blood flow per se
caused the epileptic seizures but that it probably arose from subsequent
cytotoxic effects which they could not specify.
There are few studies in the literature which evaluate the prevalence of
impairment and disability in long-term survivors, as most investigators are
concerned with selective series. Moreover, the motor function after stroke
has been measured using different methods. The observed occurrence rate
found in this investigation (IV) is close to that reported by Petlund77. It
should, though, be remembered that only cooperative patients were included.
Hence, the observed occurrence of motor impairment, ADL-disability and
decreased life satisfaction may constitute an under- rather than an
overestimation of the real occurrence. It can also reasonably be assumed that
36
the occurrence of perceptual disturbances is greater than that reported here:
Eleven non-communicable (and therefore nonassessed) patients with
cognitive disturbances were classified as suffering from (multiinfarct)
dementia and most probably had perceptual disturbances.
Usually symptom-oriented approaches are used for characterizing
perceptual deficits, which many authors regard as deficits of cerebral
integration. According to the definitions of Gibson and followers167'! 68,
perception is immediate and can, therefore, be seen as a sensing quality. The
present findings (IV) of two distinct perceptual factors of which one
represents low-order and the other represents higher-order perception
appear to substantiate Gibson's theoretical model. In this context it is
important to emphasize that, in a sample of patients examined within two
weeks after stroke, the identical model of two perceptual factors emerged201.
It is well-known that motor function is a powerful predictor of capacity to
manage self-care. With the methods used here for measuring motor function
and ADL-capacity, Fugl-Meyer and Jääskö 202 demonstrated a close
correlation between these parameters in six-year survivors of first stroke.
The present results (IV) confirm those findings but, in addition, perceptual
function is also of considerable importance as a predictor of the degree of
disturbances in self-care ADL. A search of the literature revealed no other
reports demonstrating the long-term joint effect of motor and perceptual
impairments on abilities/disabilities after stroke.
The majority of communicable (non-demented, non-aphasic) stroke
subjects reported decreases in life satisfaction (V). The 42% decrease in
global life satisfaction is clearly lower than that reported by Ahlsiö and co­
workers 17 in their two-year follow-up study. This discrepancy may partly be
explained by methodological differences. For instance, Ahlsiö and co­
workers17 used a visual analogue scale to characterize one item, that of global
life satisfaction, while the present investigation incorporated a total of seven
items. Moreover, selection criteria and follow-up time differed between the
two investigations which do, however, agree that satisfaction with life is longlastingly (permanently?) reduced after stroke. Evidently impairment and also
disability are of importance for the continuation of the premorbid quality of
life, as illustrated by significant associations between motor impairment vs
decreases in satisfaction with life in general, with leisure and with sexuality,
and also between reduced self-care ability and decreases in satisfaction with
life in general, experienced ADL and sexuality. That these decreases are the
37
long-term effects of stroke is supported by the virtually stable levels of life
satisfaction thoughout a 20-year period in non-apopletic, clinically healthy,
elderly subjects. However, a considerable proportion of non-impaired and
non-self-care disabled subjects reported decreased life satisfaction due to
stroke. Such decreases which may best be explained by the psychological
impact of stroke per se, including fear and anxiety.
It could be argued that non-normative, "subjective" measures, such as that
used for measuring life satisfaction, are insufficient because of low validity.
Judging from the generally close correspondence of levels of life satisfaction
between patients' retrospective reports of satisfaction prior to the stroke and
the actual reported life satisfaction of reference subjects, it would appear that
self-reported changes can be used as valid and reproducible measures.
Satisfaction with family life and friends changed little (V), which may
indicate that these stroke patients experienced good support from their family
and friends. However, the decreases, not only in global but also in sexual and
leisure satisfaction, point equally strongly to many patients’ ending up
frustrated and passive spectators of life. This postulation is supported by
Sjogren's findings of close correlations between decreased levels of leisure
and sexual activity and decreases in the respective levels of satisfaction!03.
The conclusion is, therefore, that much attention should be focused on
patients' premorbid values, interests and life-roles.
Stroke is a major - often catastrophic - life event for the victims and those
close to them. Hence, throughout treatment of completed stroke, the patient,
and his relatives should be seen as social human beings. If that is forgotten, we
may, with our more or less intensive medical and rehabilitation interventions,
well-intentioned though they might be, help to create a population of formally
well-functioning (in terms of impairment and disability) stroke survivors
among whom the majority of whom have lost a considerable part of the
meaningfullness of their lives.
38
ACKNOWLEDGEMENTS
To all those who have made it possible for me to write this thesis.
I would like to express my sincere gratitude and to thank, especially:
Professor Bengt Winblad, my supervisor and friend, for supplying me with the necessary
facitilies, for spurring me on, and for sacrificing his leisure time and quality of life to
enable me to finish my dissertation.
Professor Per Olov Wester, my supervisor at the Department of Medicine, for introducing
me to the cerebrovascular diseases and for his fatherly guidance and support throughout
this project.
Professor Axel R Fugl-Meyer, my supervisor at the Department of Rehabilitation
Medicine who, in 1979, enticed me to leave Kiruna for Umeå, in order to introduce me to
stroke rehabilitation and who persuaded me to adopt and employ a holistic view.
Docent Kjell Asplund, my co-worker, for teaching me in scientific methods and how to
write scientifically and for supporting my work throughout.
Dr Sture Eriksson, my colleague and co-worker, for introducing me to medical statistics,
for his criticism and his patience with my silly never-ending questions.
Mr James Hurst, BA, my co-worker and friend, for his constant willingness to help me in
my work as well as with my car repairs.
Ms Birgitta Bemspång, OT, my co-worker, for introducing me to the concepts of low and
high level perception and for making me see things from woman’s point of view.
Docent Kerstin Fugl-Meyer, my co-worker, for opening my eyes and making me realize
that life satisfaction is more than work, and patients are more than material.
Docents Erik Hägg and Folke Lithner, Drs Tommy Olsson and Tage Strand and all the
other members at the CVD Unit for their support and keen interest to help stroke patients.
Mrs Åsa Sundh for her excellent linguistic revision.
Fil lie Robert Elston for his assistance and linguistic revision.
Research assisstant Mats Långström for his illustrations.
My colleagues and the staff at the outpatient clinic, Department of Geriatric Medicine, for
their support.
The staff at the Geriatric Stroke Rehabilitation Unit, Ward 5, for their generous support
and patience. The staff at the Department of Central Patient Records for their never-ending
patience to locate old medical records.
My fiancée, "akka”, Siri for her love, support and patience.
My parents and brothers and their families for their continous support.
Last, but not least, I would like to express my sincere gratitude towards our stroke
patients and their relatives, who made this study possible.
This study was supported by grants from the Swedish Medical Research Council, the
Joint Committee of the Northern Sweden Health Region, Umeå University, King Gustav
V’s Anniversary fund, Stiftelsen för Gamla Tjänarinnor, Trygg-Hansa forskningsfond,
Borgerskapets i Umeå forskningsstiftelse, and the Medical Faculty, and Fund for Medical
Research, Umeå University.
39
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