Long-term Effects Of Stroke

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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 REFERENCES 1. Gongyuan Z. Passing on traditional Chinese medicine. Beijing Review 1985; 28: 20-26. 2. Clarke E. Apoplexy in the Hippocratic writings. Bull Hist Med 1963; 37: 301-314. 3. Aretaios. De akuta och kroniska sjukdomarnas symptomatologi och behandling. Ed. Renander A. Almqvist & Wiksell, Stockholm 1959. 4. McHenry LC jr. A history of stroke. Int J Neurology 1981; 15: 314-326. 5. Gurdjian ES, Gurdjian ES. History of occlusive cerebrovascular disease. I. From Wepfer to Moniz. Arch Neurol 1979; 36: 340-343. 6. Robins M, Baum HM. Incidence: The National Survey of Stroke. Stroke 1981; 12: (Suppl I): I-145-I-157. 7. Gross CR, Kase CS, Mohr JP, Cunningham SC, Baker WE. Stroke in South Alabama: Incidence and diagnostic features- a population based study. Stroke 1984; 15: 249-254. 8. Aho K, Harmsen P, Hatano S, Marquardsen J, Smirnov VE, Strasser T. Cerebrovascular disease in the community: results of a WHO collaborative study. Bull WHO 1980; 58: 113-130. 9. Sivenius J, Heinonen OP, Pyörälä K, Salonen J, Riekkinen P. The incidence of stroke in the Kuopio area of East Finland. Stroke 1985; 16: 188-192. 10. Walker AE, Robins M, Weifeld FD. National Survey of Stroke. Clinical findings. Stroke 1981; 12 (suppl 1): 1-13 -1-31. 11. Oxfordshire Community Stroke Project. Incidence of stroke in Oxfordshire: first year’s experience of a community stroke register. Br Med J 1983; 287: 713-717. 12. von Arbin M, Britton M, de Faire U, Helmers C, Miah K, Murray V. A study of stroke patients treated in a non-intensive stroke unit or in general medical wards. Acta Med Scand 1980; 208: 81-85. 13. Terent A. Acute cerebrovascular diseases. Uppsala, Sweden: University of Uppsala, 1980. Dissertation. 14. Eriksson S, Asplund K, Hägg E, Lithner F, Wester PO. Clinical profiles of cerebrovascular disorders in a population based patient sample. J Chronic Dis. In press. 15. Sacco RL, Wolf PA, Kannel WB, McNamara PM. Survival and recurrence following stroke. The Framingham study. Stroke 1983; 13: 290-295. 16. Chen Q, Ling R. A 1-4 year follow-up study of 306 cases of stroke. Stroke 1985; 16: 323-327. 17. Ahlsiö B, Britton M, Murray V, Theorell T. Disablement and quality of life after stroke. Stroke 1984; 15: 886-890. 18. Sjöström Å. Hospitalized cases of stroke in a Swedish hospital region, p 41. In Stroke. Engel A, Larsson T (eds). Stockholm, Nordiska Bokhandelns förlag, 1967. 19. Frithz G. Studies of cerebrovascular stroke. I. Epidemiology of first time strokes in persons under 70 years of age. Ups J Med Sci 1975; 80: 141- 147. 20. Norrving B, Nilsson B. Epidemiology of stroke in Lund, Sweden 1983-84. Changes in subtype versus age and clinical severity. Acta Neurol Scand 1986; 73: 514. 21. Asplund K, Wester PO. Epidemiology of cerebrovascular disease in Northern Sweden. Arctic Medical Research 1987; 45: 4. 22. Matsumoto N, Whisnant JP, Kurland LT, Okazaki H. Natural history of stroke in Rochester, Minnesota, 1955 through 1969: an extension of a previous study, 1945 through 1954. Stroke 1973; 4: 20-29. 23. Garraway WM, Whisnant JP, Kurland LT, O'Fallon WM. Changing pattern of cerebral infarction: 1945-1974. Stroke 1979; 10: 657-662. 24. Ueda K, Omae T, Hirota Y, Takeshita M, Katsuki S, Tanaka K, Enjoji M. Decreasing trend in incidence and mortality from stroke in Hisayama residents, Japan. Stroke 1981; 12: 154-160. 25. Kotila M. Declining incidence and mortality of stroke? Stroke 1984; 15: 255-259. 40 26. Alfredsson L, von Arbin M, de Faire U. Mortality from and incidence of stroke in Stockholm. Br Med J 1986; 292: 1299-1303. 27. Harmsen P. Stroke registret i Göteborg. Hjärnblödning och hjärninfarkt (stroke)diagnostik och behandling. SPRI, Stockholm 1986. 28. Haberman S. Sex differences in the incidence of cerebrovascular disease. J Epidemiol Community Health 1981; 35: 45-50. 29. Bonita R, Beaglehole R, North JDK. Event, Incidence and case fatality rates of cerebrovascular disease in Auckland, New Zealand. Am J Epidemiol 1984; 120: 236-243. 30. Komachi Y, Tanak H, Shimamoto T et al. A collaborative study of stroke incidence in Japan: 1975-1979. Strokel984; 15: 28-36. 31. Kagan A, Popper JS, Rhoads GG. Factors related to stroke incidence in Hawaiian Japanese men. The Honolulu heart study. Stroke 1980; 11: 14-20. 32. Diaz JF, Hachinski VC, Pederson LL, Donald A. Aggregation of multiple risk factors for stroke in siblings of patients with brain infarction and transient ischemic attacks. Stroke 1986; 17: 1239-1242. 33. Kannel WB, Me Gee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA 1978; 241: 2035-2038. 34. Abbott RD, Donahue RP, MacMahon SW, Reed DM, Yano K. Diabetes and the risk of stroke. The Honolulu Heart Program. JAMA 1987; 257: 949-952. 35. Weinberger J, Biscarra V, Weisberg MK, Jacobson JH. Factors contributing to stroke in patients with atherosclerotic disease of the great vessels: the role of diabetes. Stroke 1983; 14: 709-712. 36. Wolf PA. Hypertension as a risk factor for stroke. In: Whisnant JP and Sandok B (eds.): Cerebral vascular diseases. New York, Grune and Stratton, 1975; 105-112. 37. Lin CH, Shimizu Y, Kato H, Robertson TL, Furonaka H, Kodarna K, Fukunaga Y. Cerebrovascular diseases in a fixed population of Hiroshima and Nagasaki, with special reference to relationship between type and risk factors. Stroke 1984; 15: 653660. 38. von Arbin M, Britton M, de Faire U, Tisell Å. Circulatory manifestations and risk factors in patients with acute cerebrovascular disease and in matched controls. Acta Med Scand 1985; 218: 373-380. 39. W olf PA, Dawber TR, Kannel WB. Heart disease as a precursor of stroke. Advances of neurology, vol. 19, ed. BS Schoenberg. Raven Press, New York © 1978. 40. Herman B, Schmitz PIM, Leyten ACM, van Luijk JH, Frenken CWGM, Op de Coul AAW, Schulte BPM. Multivariate logistic analysis of risk factors for stroke in Tilburg, the Netherlands. Am J Epidemiol 1983; 118: 514-525. 41. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation. The Framingham study. N Engl J Med 1982; 306: 1018- 1022. 42. 43. 44. 45. 46. 47. 48. Cartlidge NEF, Whisnant JP, Elveback LR. Carotid and vertebral-basilar transient cerebral ischemic attacks. Mayo Clin Proc 1977; 52: 117-120. Muuronen A, Kaste M, Outcome of 314 patients with transient ischemic attacks. Stroke 1982; 13:24-31. Hass WK. Aspirin for the limping brain (editorial). Stroke 8: 299, 1977. Bonita R, Scragg R, Stewart A, Jackson R, Beaglehole R. Cigarette smoking and risk of premature stroke in men and women. Br Med J 1986; 293: 6-8. Hillbom M, Kaste M. Ethanol intoxication: a risk factor for ischemic brain infarction. Stroke 1983; 14: 694-699. Donahue RP, Abbott RD, Reed DM,*Yano K. Alcohol and hemorrhagic stroke. The Honolulu Heart Program. Jama 1986; 255: 2311-2314. Gorelik PB. Alcohol and stroke. Stroke 1987; 18: 268-271. 41 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. Byken ML, Wolf PA, Barnett HJM et al. Risk factors in stroke. A statement for physicians by the subcommittee on risk factors and stroke of the Stroke Council. Stroke 1984; 15: 1105-1111. Gordon T, Castelli WP, Hjortland MC et al. High-density lipoproteins as a protective factor against coronary heart disease: The Framingham study. Am J Med 1977; 62: 707-714. Salonen JT, Puska P, Tuomilehto J, Homan K. Relation of blood pressure, serum lipids and smoking to the risk of cerebral stroke. Stroke 1982; 13: 327-333. Tilvis RS, Erkinjuntti T, Sulkava R, Färkkilä M, Miettinen TA. Serum lipids and fatty acids in ischemic strokes. Am Heart J 1987; 113: 615-619. Salonen JT, Puska P, Tuomilehto J. Physical activity and risk of myocardial infarction, cerebral stroke and death. Am J Epidemiol 1982; 115: 526-537. Whisnant JP, Cartlidge NEF, Elveback LR. Carotid and vertebral-basilar transient ischemic attacks: effects of anticoagulants, hypertension, cardiac disorders on survival and stroke occurrence - population study. Ann Neurol 1978; 3: 107-115. Marshall J. A trial of long-term hypotensive therapy in cerebrovascular disease. Lancet 1964; 1: 10-12. Carter AB. Hypotensive therapy in stroke survivors. Lancet 1970; 1: 485-489. Beevers DG, Fairman MJ, Hamilton M, Horpur IE. Antihypertensive treatment and the course of established cerebral disease. Lancet 1973; 1: 1407-1409. Marquardsen J. The natural history of acute cerebrovascular disease. Acta Neurol Scand 1969; 45. Robins M, Baum HM. The National Survey of Stroke. Incidence. Stroke 1981; 12 (suppl I) :I-45 -1-57. Miettinen TA, Huttunen JK, Naukkarinen V, Strandberg T, Mattila S, Kumlin T, Sama S. Multifactorial primary prevention of cardiovascular diseases in middle-aged men. JAMA 1985; 254: 2097-2102. Multiple Risk Factor Intervention Trial. JAMA 1982; 248: 1465-1477. Veterans Administration Cooperative study group on Antihypertensive agents. Effects of treatment on morbidity in hypertension. II. JAMA 1970; 213: 1143-1152. McFate Smith W. Treatment of mild hypertension. Results of a ten year intervention trial. U.S. Public health Service Hospitals Cooperative Study Group. Circ Res 1977; 40 (suppl I): 98-105. Hypertension detection and follow-up program cooperative group. Five-year findings of the hypertension detection and follow-up program. JAMA 1979; 242: 2562-2571. Management committee. The Australian therapeutic trial in mild hypertension. Lancet 1980; 1: 1261-1267. Medical Research Working Party. MRC trial of treatment of mild hypertension: principal results. Br Med J 1985; 291: 97-104. The IPPPSH Collaborative Group. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). J Hypertens 1985; 3: 379-392. Tuomilehto J, Nissinen A, Wolf E, Geboers J, Piha T, Puska P. Effectiveness of treatment with antihypertensive drugs and trends in mortality from stroke in the community. BrMed J 1985; 291: 857-861. Amery A, Brixko P, Clement D et al. Mortality and morbidity results from European Working Party on High Blood Pressure in the Elderly Trial. Lancet 1985; 1: 13491354. Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. BrM edJ 1986; 293: 1145-1151. Sherman DG, Dyken ML, Fischer M, Harrison MJG, Hart RG. Cerebral embolism. Chest 1986; 89 (suppl): 82S-98S. 42 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. Koski K. Threatened stroke. Turku, Finland: University o f Turku, 1987. Dissertation. Fields WS, Lemak NA, Frankowski RF, Hardy RJ. Controlled trial of aspirin in cerebral ischemia. Stroke 1977; 8: 301-315. Reuther R, Domdorf W. Aspirin in patients with cerebral ischemia and normal angiograms or non-surgical lesions. The results of a double-blind trial. In: Breddin K, Domdorf W, Loew D, Marx R, eds. Acetylsalicyclic acid in cerebral ischaemia and coronary heart disease. Stuttgart: FK Schattauer Verlag, 1978; 97-106. Logan W, Cushion A. Studies on medical and population subjects no. 14. Morbidity statistics from general practice, Vol. I. London: H. M. Stationery Office, 1958. Matsumoto N, Whisnant JP, Kurland LT, Okazaki H. Natural history of stroke in Rochester, Minnesota, 1955 through 1969: an extension of a previous study, 1945 through 1954. Stroke 1973; 4: 20-29. Petlund C: Prevalence and invalidity from stroke in Aust-Agder county of Norway. Oslo: Universitetsförlaget, 1970. Aho K, Reunanen A, Aromaa A, Knekt P, Maatela J. Prevalence of stroke in Finland. Stroke 1986; 17: 681-686. Sprensen PS, Boysen G, Jensen G, Schnor P. Prevalence of stroke in a district of Copenhagen. Acta Neurol Scand 1982; 66: 68-81. WHO: International Classification of Impairments, Disabilities, and Handicaps. Geneva: World Health Organization, 1980. Fugl-Meyer AR, Fugl-Meyer K. Coping with traumatic brain injury. Scand J Rehab Med (suppl). In press, 1987. Jongbloed L. Prediction of function after stroke: A critical review. Stroke 1986; 17: 765-776. Feigenson JS. Stroke rehabilitation. Outcome studies and guidelines for alternative levels of care. Stroke 1981; 12: 372-375. Strand T, Asplund K, Eriksson S, Hägg E, Lithner F, Wester PO. A Non-Intensive Stroke Unit reduces functional disability and the need for long-term hospitalization. Stroke 1985; 16: 29-34. Sivenius J, Pyörälä K, Heinonen OP, Salonen JT, Riekkinen P. The significance of intensity of rehabilitation of stroke - a controlled trial. Stroke 1985; 16: 928-931. Kotila M, Waltimo O, Niemi ML, Laaksonen R, Lempinen M. The profile of recovery from stroke and factors influencing outcome. Stroke 1984; 15: 1039-1044. Vallar G, Perani D. The anatomy of unilateral neglect after right hemisphere stroke lesions. A clinical/CT-scan correlation study in man. Neuropsychologia 1986; 24: 609-622. Hurwitz LJ, Adams GF. Rehabilitation of hemiplegia: indices of assessment and prognosis. Br Med J 1972; 1: 94-98. Denes G, Semenza C, Stoppa E, Lis A. Unilateral spatial neglect and recovery from hemiplegia. A follow-up study. Brain 1982; 105: 543-552. Kinsella G, Ford B. Hemi-inattention and recovery patterns of stroke patients. Int Rehabil Med 1985; 7: 102-106. Hier DB, Mondlock J, Caplan LR. Recovery of behavioral abnormalities after right hemisphere stroke. Neurology 1983; 33: 345-350. Sinatra MG, Boeri R, Del Ton F, Fornari M, Musicco M, Girotti F. Neuropsychological evaluation in transient ischaemic attack and minor stroke. J Neurol 1984; 231: 194-197. Robinson RG, Bolla-Wilson K, Kaplan E, Lipsey JR, Price TR. Depression influences intellectual impairment is stroke patients. Br J Psychiatry 1986; 148: 541547. Ebrahim S, Nouri F, Barer D. Cognitive impairment after stroke. Age Ageing 1985; 14: 345-350. Kitagawa Y, Meyer JS, Tachibana H, Mortel KF, Rogers RL. CT-CBF correlations of cognitive deficits in multi-infarct dementia. Stroke 1984; 15: 1000-1009. 43 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. Espmark S. Stroke before 50. Scand J Rehab Med Suppl 2, 1973. Binder LM. Emotional problems after stroke. Stroke 1984; 15: 174-177. Robinson RG, Price TR. Post-stroke depressive disorders: a follow-up study of 103 patients. Stroke 1982; 13: 635-640. House A. Depression after stroke. Br Med J 1987; 294: 76-78. Parikh RM, Lipsey JR, Robinson RG, Price TR. Two-year longitudinal study of post-stroke mood disorders: dynamic changes in correlates of depression at one and two years. Stroke 1987; 18: 579-584. Weinstein EA, Kahn RL. Denial of illness. Springfield: Charles C Thomas, 1955. Ullman M. Behavioral changes in patients following strokes. Springfield: Charles C Tomas Pubi, 1962. Sjögren K. Sexuality and leisure after stroke. Umeå, Sweden: Umeå University, 1982. Dissertation. Hyman MD. The stigma of stroke. Geriatrics 1971; 26: 132-142. Wade DT, Hewer RL, Skilbeck CE, David RM. Stroke. A critical approach to diagnosis, treatment, and management. London: Chapman and Hall Ltd, 1985. Garraway WM, Akhtar AJ, Hockey L, Prescott RJ. Management of acute stroke in the elderly: follow-up of a controlled trial. Br Med J 1980; 281: 827-829. Stevens RS, Ambler NR, Warren MD. A randomized controlled trial of a stroke rehabilitation ward. Age Ageing 1984; 13: 65-75. Wood-Dauphinee S, Shapiro D, Bass E, Fletcher C, Georges P, Hensby P, Mendelsohn B. A randomized trial of team care following stroke. Stroke 15: 864872, 1984. Sivenius J, Pyörälä K, Heinonen OP, Salonen JT, Riekkinen P. The significance of intensity of stroke- a controlled trial. Stroke 1985; 16: 928-931.Dubbla Andrews K, Brocklehurst JC, Richards B, Laycock PJ. The influence of age on the clinical presentation and outcome of stroke. Int Rehabil Med 1984; 6: 49-53. Fugl-Meyer AR, Jääskö L, Norlin V. The post-stroke hemiplegic patient. Scand J Rehab Med 1975; 7: 73-83. Sjögren K. Leisure after stroke. Int Rehab Med 1982; 4: 80-87. Trudel L, Fabia J, Bouchard J-P. Quality of life of 50 carotid endarterectomy survivors: a long-term follow-up study. Arch Phys Med Rehabil 1984; 65: 310-312. Labi MLC, Phillips TF, Gresham GE. Psychosocial disability in physically restored long-term stroke survivors. Arch Phys Med Rehabil 61: 561-565, 1980. Dowd JJ, Bengtson VL. Aging in a minority population: An examination of the double jeopardy hypotheses. J Gerontol 1978; 33: 427-436. Najman JM, Levine S. Evaluating the impact of medical care and technologies on the quality of life: a review and critique. Soc Sci Med 1981; 15F: 107-115. Schuessler KF, Fisher GA. Quality of life research and sociology. Ann Rev Sociol 1985; 11: 129-149. Baum HM, Robins M. The National Survey of Stroke. Survival and prevalence. Stroke (suppl I) 1981; 12:1-59 -1-68. Whisnant JP. The decline of stroke Stroke 1985; 15: 160-168. Manton KG, Baum HM. CVD mortality, 1968-1978: observations and implications. Stroke 1984; 15:451-457. Gillum RF, Gomez-Martin O, Kottke TE et al. Acute stroke in a metropolitan area 1970 and 1980. The Minnesota heart survey. 1985; 38: 891-898. Prineas RJ. Cerebrovascular disease occurrence in Australia. Med J Aust 1971; 2: 509-515. Hu H-H, Chu F-L, Wong W-J, Lo Y-K, Sheng W-Y. Trends in mortality from cerebrovascular disease in Taiwan. Stroke 1986; 17: 1121-1125. Kotila M. Declining incidence and mortality of stroke? Stroke 1984; 15: 255-259. La Vecchia C, Decarli A. Trends in mortality from cerebrovascular disease in Italy 1955-78. Stroke 1986; 17: 234-240. 44 126. Torvik A, Stenwig JT. Changes in frequency of cerebrovascular diseases in Oslo, Norway, 1958-1977. An autopsy study. Stroke 1981; 12: 816-823. 127. Abu-Zeid HAH, Choi NW, Hsu P-H, Maini KK. Prognostic factors in the survival of 1484 stroke cases observed for 30 to 48 months. II. Stroke 1978; 35: 213-218. 128. Miah K, von Arbin M, Britton M, de Faire U, Helmers C, Maasing R. Prognosis in acute stroke with special reference to some cardiac factors. J Chronic Dis 1983; 36: 279-288. 129. Howard G, Walker MD, Becker C et al. Community hospital-based stroke programs: North Carolina, Oregon, and New York. III. Factors influencing survival after stroke: proportional hazards analysis of 4219 patients. Stroke 1986; 17: 294299. 130. Solzi P, Ring H, Najenson T, Luz Y. Hémiplégies after a first stroke: late survival and risk factors. Stroke 1983; 14: 703- 709. 131. Chambers BR, Norris JW, Shurvell BL, Hachinski VC. Prognosis of acute stroke. Neurology 1987; 37: 221-225. 132. Masuda J, Tanaka K, Omae T, Ueda K, Sadoshima S. Cerebrovascular diseases and the underlying vascular lesions in Hisayama, Japan - a pathological study of autopsy cases. Stroke 1983; 14: 934-940. 133. Kaste M, Somer H, Konttinen A. Heart type creatine kinase isoenzyme (CKMB) in acute cerebral disorders. Br Heart J 1978; 40: 802-805. 134. Pfeiffer FE, Homburger HA, Yanagihara T. Serum creatine kinase B concentrations in acute cerebrovascular diseases. Arch Neurol 1984; 41: 1175-1178. 135. Norris JW, Hachinski VC, Myers MG, Callow J, Wong T, Moore RW. Serum cardiac enzymes in stroke. Stroke 1979; 10: 548-553. 136. Norris JW, Froggratt GM, Hachinski VC. Cardiac arrhythmias in acute stroke. Stroke 1978; 9: 392-396. 137. Britton M, de Faire U, Helmers C, Miah K, Ryding C, Wester PO. Arrhythmias with acute cerebrovascular disease. Acta Med Scand 1979; 205: 425-428. 138. Kolin A, Norris JW. Myocardial damage from acute cerebral lesions. Stroke 1984; 15: 990-993. 139. von Arbin M, Britton M, de Faire U, Helmers C, Miah K, Murray V. Myocardial infarction in patients with acute cerebrovascular disease. Eur Heart J 1982; 3: 136141. 140. Rokey R, Rolak LA, Harati Y, Kutka N, Vernai MS. Coronary artery disease in patients with cerebrovascular disease: a prospective study. Ann Neurol 1984; 16: 5053. 141. Groch SN, McDevitt E, Wright IS. A long-term study of cerebral vascular disease. Ann Intern Med 1961; 55: 358-367. 142. Enger E, Bpyesen S. Long-term anticoagulant therapy in patients with cerebral infarction. Acta Med Scand 1965; (Suppl 438). 143. Leonberg SC, Elliott FA. Prevention of recurrent stroke. Stroke 1981; 12: 731-735. 144. A Swedish Cooperative Study. High-dose acetylsalicylic acid after cerebral infarction. Stroke 1987; 18: 325-334. 145. Persantin aspirin trial in cerebral ischemia. Part II: endpoints and results. Stroke 1985; 16: 406-415. 146. Gent M, Blakely JA, Hachinski V, et al. A secondary prevention, randomized trial of suloctidil in patients with a recent history of thromboembolic stroke. Stroke 1985; 16: 416-424. 147. Shinton RA, Gill JS, Zezulka AV, Beevers DG. The frequency of epilepsy preceding stroke. Case-control study in 230 patients. Lancet 1987; 1: 11-13. 148. Richardson EP jr, Dodge PR. Epilepsy in cerebral vascular disease. Epilepsia 1954; 3: 49-74. 149. Pirttimäki R, Narva EV, Ruikka I. Epilepsy as a sequel to cerebrovascular accident. Scand J Soc Med 1977; 14 (Suppl): 134-140. 45 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. Rosenkvist L, Skyh0j Olsen T. Epilepsy after cerebral infarction. Acta Neurol Scand 1986; 73: 548. Strand T. Stroke. Patient characteristics, efficacy of a stroke unit and evaluation of hemodilution therapy. Umeå, Sweden: Umeå University, 1986. Dissertation. Eriksson S, Asplund K, Hägg E, Lithner F, Strand T, Wester PO. Clinical profiles of cerebrovascular disorders in a population based patient sample. J Chronic Dis. (In press). Strand T, Asplund K, Eriksson S, Hägg E, Lithner F, Wester PO. Stroke unit care who benefits? Comparison with medical care in relation to prognostic indicators on admission. Stroke 1986; 17: 377-381. World Health Organization: Proposal for the multinational monitoring of trends and determinants in cardiovascular disease (MONICA Project). WHO/MNC/82. 1 Rev 1. 1983. Hypertension and coronary heart disease: Classification and criteria for epidemiological studies. Report of a WHO expert committee. World health organization technical reports Series 1959; 168: 25-28. Brain’s diseases of the nervous system (revised by the late Lord Brain; Walton JN). London: Oxford University Press, 1969. Fugl-Meyer AR, Jääskö L, Leyman I, Olsson S, Steglind S. Post-stroke hemiplegic patient. I: a method for evaluation of physical performance. Scand J Rehab Med 1975; 7: 13-31. Twitchell TE. The restoration of motor function following hemiplegia in man. Brain 1951; 74: 443-480. Duncan DW, Probst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther 1983; 63: 1606-1610. DeWeerdt WJG, Harrison MA. Measuring recovery of arm-hand function in stroke patients: A comparison of the Brunnstrom - Fugl-Meyer test and the action research arm test. Physiother Can 1985; 37: 65-70. Nachenson T, Rachmani L, Elazar B, Averbuch S. An elementary cognitive assessment and treatment of the craniocerebrally injured patient. In: Edelstein B, Tcouture E, eds. Behavioral assessment and rehabilitation of traumatically brain damaged. New York: Plenum Press, 1984. Folstein MF, Folstein SE, McHugh PR. 'Mini-Mental State'. A practical method for grading the cognitive state of patients for clinician. J Psychiatr Res 1975; 12: 189198. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to changes. Brit J Psychiat 1979; 134: 382-389. Fugl-Meyer AR, Jääskö L. Post-stroke hemiplegia and ADL-performance. Scand J Rehab Med 1980; Suppl No 7: 140-152. Peto R, Pike MC, Armitage P et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 1977; 35: 1-39. Cox DR. Regression models and life tables. J R Stat Soc B 1972; 34: 187-220. Gibson J. The senses considered as perceptual system. BostonMA: Houghton Mifflin,1966. Shepard RN. Ecological constraints on internal representation: resonant kinematics of perceiving, imagining,thinking, and dreaming. Psychol Rev 1984; 91: 417-447. Svanborg A. Åldrandet. In: Steen B, Svanborg A. Geriatrik och långvårdsmedicin. (Natur och Kultur). Arlöv: Berlings, 1983; 7-14. Ulbrich J. Woran sterben die Apoplektiker. Ther Umsch 1981; 38: 703-708. Bounds JV, Wiebers DO, Whisnant JP, Okazaki H. Mechanism and timing of deaths from cerebral infarction. Stroke 1981; 12: 474-477. Khaw K-T, Barrett-Connor E, Suarez L, Criqui MH. Predictors of stroke-associated mortality in the elderly. Stroke 1984; 15: 244-248. 46 173. Marshall J, Kaeser AC. Survival after non-haemorrhagic cerebrovascular accidents. Br Med J 1961; 2: 73-77. 174. Haerer AF, Woosley PC. Prognosis and quality of survival in a hospitalized stroke population from the South. Stroke 6: 543-548, 1975. 175. Baker RN, Schwartz WS, Ramseyer JC. Prognosis among survivors of ischemic stroke. Neurology 1968; 18: 933-941. 176. The CONSENSUS trial study goup. Effects of enalapril on mortality in severe congestive heart failure. New Engl J Med 1987; 316: 1429-1435. 177. Robinson RW, Demirei M, LeBeau RJ. Natural history of cerebral thrombosis nine to nineteen year follow-up. J Chronic Dis 1961; 21: 221-230. 178. Sievers J. Myocardial infarction. Acta Med Scand 1964; 175 (suppl 406). 179. Konu V. Myocardial infarction in the elderly. Acta Med Scand 1977; suppl 604. 180. Walter P, Neil-Dwyer G, Cruickshank JM. Beneficial effects of adrenergic blockade in patients with subarachnoidal haemorrhage. Br Med J 1982; 284: 1661-1664. 181. Kinnander G, Viitanen M, Asplund K. b-adrenergic blockade after stroke. A preliminary closed cohort study. Stroke 1987; 18: 240-243. 182. Asplund K, Helmers C, Lithner F, Strand T, Wester PO. The natural history of stroke in diabetic patients. Acta Med Scand 1980; 207: 417-424. 183. Fuller JH, Shipley MJ, Rose G, Jarret RJ, Keen H. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study. Br Med J 1983; 287: 867-870. 184. Oppenheimer SM, Hoffbrand BI, Oswald GA, Yudkin JS. Diabetes mellitus and early mortality from stroke. Br Med J 1985; 291: 1014-1015. 185. Cox NH, Lorains JW. The prognostic value of blood glucose and glycosylated haemoglobin estimation in patients with stroke. Postgrad Med J 1986; 62: 7-10. 186. Wilson PWF, Kannel WB, Anderson KM. Lipids; glucose intolerance and vascular disease: the Framingham study. Monogr Atheroscler 1985; 13: 1-11. 187. Smith JW, Marcus FI, Serokman R. Multicenter postinfarction research group. Prognosis of patients with diabetes mellitus after acute myocardial infarction. Am J Cardiol1984; 54:718-721. 188. Berger L, Hakim AM. The association of hyperglycemia with cerebral edema in stroke. Stroke 1986; 17: 865-871. 189. Duckrow RB, Beard DC, Brennan RW. Regional cerebral blood flow decreases during chronic and acute hyperglycemia. Stroke 1987 18: 52-58. 190. Rehncrona St. Molecular mechanisms for ischemic brain damage and aspects on protection. Acta Neurochir 1986; 36 (Suppl 1): 125-128. 191. Johnson SE, Skre H. Transient cerebral ischemic attacks in the young and middle aged. A population study. 1986; 17: 662-666. 192. Adams Jr HP, Kassell NF, Mazuz H. The patient with transient ischemic attacks-Is this the time for a new therapeutic approach? Stroke 1984; 15: 371-375. 193. Di Pasquale G, Andreoli A, Pinelli G, Grazi P, Manini G, Tognetti F, Testa C. Cerebral ischemia and asymptomatic coronary artery disease: A prospective study of 83 patients. Stroke 1986; 17: 1098-1101. 194. Windebank WJ. Diagnosing pulmonary embolism. Br Med J 1987; 294: 1369-1370. 195. Prasad BK, Banerjee AK, Howard H. Incidence of deep vein thrombosis and effect of pneumatic compression of the calf in elderly hémiplégies. Age Ageing 1982; 11: 42-44. 196. Mellbring G, Strand T, Eriksson E. Venous tromboembolism after cerebral infarction and prophylactic effect of dextran 40. Acta Med Scand 1986; 61: 425-429. 197. Turpie AGG, Levine MN, Hirsh et al. Double-blind randomised trial of org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke. Lancet 1987; 1: 523-526. 198. Skyhpj Olsen T. Factors of importance for development of epilepsy in patients with cerebral infarction. (Abstract). Scandinavian Congress of Neurology, Bergen 1982. 47 199. Hornig CR, Busse O, Domdorf W. Epileptische Anfälle nach Himinfarkten. Ätiologie, Klinik, CT-Befunde. Nervenarzt 1984; 55: 525-529. 200. Lesser RP, Lüders H, Dinner DS, Morris HH. Epileptic seizures due to thrombotic and embolic cerebrovascular disease in older patients. Epilepsia 1985; 26: 622-630. 201. Eriksson S, Bemspång B, Fugl-Meyer. Perceptual and motor impairment within two weeks after stroke. A multifactorial statistic approach. Occ Ther J Res. (In press). 202. Fugl-Meyer AR, Jääskö L. Post-stroke hemiplegia and ADL-performance. Scand J Rehab Med 1980; Suppl 7: 140-152. 48