Long term survival after primary intracerebral haemorrhage: a retrospective population based study.

OBJECTIVES: To determine the long term survival and predictors of death in patients with primary intracerebral haemorrhage (ICH) in Central Finland. METHODS: Data were collected retrospectively on all adult patients with first ever ICH in Central Finland county between September 1985 and December 1991. The survival of all patients at the end of December 2002 was investigated. Kaplan-Meier survival curves were constructed and factors associated with both early (< or =28 days) and late deaths determined. Long term survival was compared with the general Finnish population of the same age and sex distribution. The causes of death were compared with those of the population of Central Finland. RESULTS: 411 patients with first ever ICH were identified, 199 men (mean age 64.9 years) and 212 women (mean age 69.5); 30 died before hospital admission, and 208 (50.6%) within the first 28 days. In Kaplan-Meier analysis, at 16 years the cumulative survival was 3.2% for men and 9.8% for women. The 28 day survivors had a 4.5-fold increased annual risk of dying during the first year after ICH, and 2.2-fold during years 2 to 6. On admission, significant independent predictors of death within the first four weeks were unconsciousness, lateral shift of cerebral midline structures, mean arterial pressure > or =134 mm Hg, hyperglycaemia, anticoagulant treatment, and ventricular extrasystoles. Predictors of late death for the 28 day survivors were old age, male sex, and heart failure. CONCLUSIONS: Primary intracerebral haemorrhage has a poor short and long term outcome. The results emphasise the importance of primary and secondary prevention for ICH.

Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study.

BACKGROUND: The role of admission blood glucose level on the prognosis of patients with intracerebral haemorrhage has not been elucidated. OBJECTIVE: To examine this association on the basis of an epidemiologically representative patient material. METHODS: 249 500 people living in the catchment area of the Central Hospital of Central Finland. The diagnosis of ICH was established if verified by cranial computed tomography (CT) or autopsy. RESULTS: Of the 416 patients who fulfilled the diagnostic criteria, 30 died before admission and 386 were admitted to the Central Hospital. All 329 patients (290 nondiabetics and 39 diabetics) with both admission blood glucose and cranial CT data were included in the study. The mean blood glucose level was 10.6 mmol/l for nondiabetics who died on the day of onset, 8.6 mmol/l for those dying during days 1 to 28, and 6.8 mmol/l for the 28 day survivors. The corresponding figures for diabetics were 13.9 mmol/l, 12.5 mmol/l, and 9.3 mmol/l. In both nondiabetics and diabetics, patients who died had significantly higher mean glucose than the 28 day survivors (p<0.0001 versus p = 0.029). However, blood glucose of the surviving diabetics was as high as that of the deceased nondiabetics (9.3 mmol/l versus 9.1 mmol/l). In nondiabetics, admission blood glucose was associated with parameters signifying severe stroke; disturbed consciousness, large haematoma volume and shift of cerebral midline structures, and high admission mean arterial pressure. In logistic regression analysis, high admission blood glucose in nondiabetics was a significant predictor of death during the first 28 days of onset (odds ratio 1.22, 95% CI 1.07 to 1.40). CONCLUSIONS: High admission blood glucose predicts increased 28 day case fatality rate in both nondiabetic and diabetic patients with ICH. Because high admission blood glucose was associated with markers of severe stroke, we are inclined to support the stress theory; high admission blood glucose is the result of a serious ICH.

Blood pressure, nimodipine, and outcome of ischemic stroke.

OBJECTIVES: The reduction of blood pressure (BP) caused by nimodipine has been proposed as an explanation for the poor results in ischemic stroke trials. We evaluated further the relationships between BP, nimodipine, and outcome of ischemic stroke, and also searched for other possible explaining mechanisms. PATIENTS AND METHODS: All 350 participants of an earlier placebo controlled trial on oral nimodipine were included in this study. Among other variables, the admission BP, and the change of BP during the first day were noted. The 3 week and 3 month functional outcome was assessed with a modified Rankin grading. RESULTS: The severity of stroke was the utmost important predictor of outcome. Visible cerebral infarction on computed tomography (CT) was associated with severe stroke and an early commencement (within 24 h of stroke onset) of nimodipine treatment. In the nimodipine arm, high initial systolic and diastolic BP measured < or =24 h of stroke onset were independent predictors of good functional outcome (Rankin grades 1 and 2), whereas BP change was not. The survivors in the nimodipine arm with mild to moderately severe stroke had higher initial BP than the deceased ones, in severe strokes the situation was the opposite. CONCLUSIONS: Stroke severity, visible cerebral infarcts on CT, and early commencement of nimodipine treatment were associated. Overall, high initial systolic and diastolic BP predicted a good functional outcome in patients on nimodipine. In severe strokes, the combination of nimodipine and high initial BP was associated with increased risk of death.

Smoking and intervertebral disc degeneration.

Cigarette smokers have an increased risk of low back pain which may be caused by disc degeneration and spinal instability, for example. Ischemia, apoptosis, faulty synthesis of disc macromolecules, and an imbalance between disc matrix proteinases and their inhibitors may be involved in the pathogenesis of disc degeneration. Along with degeneration, the primary avascular disc turns vascular. There is some evidence that disc degeneration of cigarette smokers is of more severe degree than that of non-smokers.Cigarette-smoking increases serum proteolytic activity by releasing proteolytic enzymes from neutrophils in alveolar capillaries, and by inhibiting the activity of alpha-1-antiprotease, the most potent protease inhibitor. We hypothesize that the high serum proteolytic activity of cigarette-smokers gets access to a previously degenerated neovascularized disc and speeds up the degerative process. The increased proteolytic activity may also weaken the spinal ligaments resulting in spinal instability. These processes may explain the increased risk of low back pain of cigarette smokers.

Vitamin E and beta carotene supplementation in high risk for stroke: a subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

CONTEXT: High serum or dietary levels of vitamin E and beta carotene appear to be associated with lower risk of stroke, but studies regarding their supplementation have not supported their use in stroke prevention. OBJECTIVE: To determine if vitamin E (dl-alpha tocopherol) and beta carotene supplementations could be used in prevention of stroke in men at high risk for hemorrhagic or ischemic events. DESIGN: Population-based, randomized, double-blind, placebo-controlled, 2 x 2 factorial design trial (the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study), conducted from April 1985 through April 30, 1993, with median follow-up of 6 years. INTERVENTIONS: Alpha tocopherol, 50 mg; beta carotene, 20 mg; both; or placebo. PARTICIPANTS: From the total male population aged 50 through 69 years in southwestern Finland (n = 290,406), 29,133 male smokers were randomized to 1 of 4 treatment regimens. We excluded 614 men because of previous stroke at baseline, leaving 28, 519. MAIN OUTCOME MEASURES: Incident and fatal subarachnoid and intracerebral hemorrhage, cerebral infarction, and unspecified stroke. RESULTS: Stroke occurred in a total of 1057 men: 85 had subarachnoid and 112 had intracerebral hemorrhage, 807 had cerebral infarction, and 53 had unspecified stroke. Within 90 days from onset, 160 men died of stroke. Vitamin E supplementation increased the risk of subarachnoid hemorrhage (relative risk [RR], 2.45; 95% confidence interval [CI], 1.08-5.55) and decreased risk of cerebral infarction (RR, 0.70; 95% CI, 0.55-0.89) in hypertensive men but had no effect among normotensive men. Furthermore, it decreased the risk of cerebral infarction, without elevating the risk of subarachnoid hemorrhage, among hypertensive men with concurrent diabetes (RR, 0.33; 95% CI, 0.14-0.78). Beta carotene supplementation appeared to increase the risk of intracerebral hemorrhage and modestly decrease that of cerebral infarction among men with greater alcohol consumption. CONCLUSION: Vitamin E supplementation may prevent ischemic stroke in high-risk hypertensive patients, but further studies are needed. Arch Neurol. 2000;57:1503-1509

Effect of nimodipine on final infarct volume after acute ischemic stroke.

Placebo-controlled clinical trials with nimodipine in acute ischemic stroke have not fulfilled the early optimistic expectations. Nimodipine has in some experimental studies, when administered either before or up to 90 min after induction of cerebral ischemia, resulted in a reduction of infarct size. No studies on the effects of nimodipine on infarct size in man have been published. We measured the infarct volumes in the admission and control CT examinations 3 weeks to 3 months later in 153 patients who had participated in a multicenter, randomized and placebo-controlled study. No statistically significant differences overall were found within or between the treatment groups. Subgroup analyses revealed in the placebo, but not in the nimodipine arm, an increase in the median infarct volumes if the treatment was started within 24 h of onset, and if the volume in the admission CT was less than median. A beneficial effect of nimodipine in prevention of infarct size increase in these circumstances cannot be excluded.

Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers.

Observational data suggest that diets rich in fruits and vegetables and with high serum levels of antioxidants are associated with decreased incidence and mortality of stroke. We studied the effects of alpha-tocopherol and beta-carotene supplementation. The incidence and mortality of stroke were examined in 28 519 male cigarette smokers aged 50 to 69 years without history of stroke who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study). The daily supplementation was 50 mg alpha-tocopherol, 20 mg beta-carotene, both, or placebo. The median follow-up was 6.0 years. A total of 1057 men suffered from incident stroke: 85 men had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke. Deaths due to stroke within 3 months numbered 38, 50, 65, and 7, respectively (total 160). alpha-Tocopherol supplementation increased the risk of subarachnoid hemorrhage 50% (95% CI -3% to 132%, P=0.07) but decreased that of cerebral infarction 14% (95% CI -25% to -1%, P=0.03), whereas beta-carotene supplementation increased the risk of intracerebral hemorrhage 62% (95% CI 10% to 136%, P=0.01). alpha-Tocopherol supplementation also increased the risk of fatal subarachnoid hemorrhage 181% (95% CI 37% to 479%, P=0.01). The overall net effects of either supplementation on the incidence and mortality from total stroke were nonsignificant. alpha-Tocopherol supplementation increases the risk of fatal hemorrhagic strokes but prevents cerebral infarction. The effects may be due to the antiplatelet actions of alpha-tocopherol. beta-Carotene supplementation increases the risk of intracerebral hemorrhage, but no obvious mechanism is available.

Different risk factors for different stroke subtypes: association of blood pressure, cholesterol, and antioxidants.

BACKGROUND AND PURPOSE: Blood pressure is an important risk factor for stroke, but the roles of serum total and HDL cholesterol, alpha-tocopherol, and beta-carotene are poorly established. We studied these factors in relation to stroke subtypes. METHODS: Male smokers (n=28 519) aged 50 to 69 years without a history of stroke participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a controlled trial to test the effect of alpha-tocopherol and beta-carotene supplementation on cancer. From 1985 to 1993, a total of 1057 men suffered from primary stroke: 85 had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke. RESULTS: Systolic blood pressure > or = 160 mm Hg increased the risk of all stroke subtypes 2.5 to 4-fold. Serum total cholesterol was inversely associated with the risk of intracerebral hemorrhage, whereas the risk of cerebral infarction was raised at concentrations > or = 7.0 mmol/L. The risks of subarachnoid hemorrhage and cerebral infarction were lowered with serum HDL cholesterol levels > or = 0.85 mmol/L. Pretrial high serum alpha-tocopherol decreased the risk of intracerebral hemorrhage by half and cerebral infarction by one third, whereas high serum beta-carotene doubled the risk of subarachnoid hemorrhage and decreased that of cerebral infarction by one fifth. CONCLUSIONS: The risk factor profiles of stroke subtypes differ, reflecting different etiopathology. Because reducing atherosclerotic diseases, including ischemic stroke, by lowering high serum cholesterol is one of the main targets in public health care, further studies are needed to distinguish subjects with risk of hemorrhagic stroke. The performance of antioxidants needs confirmation from clinical trials.

Alcohol consumption and stroke incidence in male smokers.

BACKGROUND: Studies on alcohol consumption and incidences of stroke subtypes have suggested distinct dose-response relationships. Blood pressure and HDL cholesterol mediate the effect of alcohol on coronary heart disease, but similar evidence on cerebrovascular diseases is not available. METHODS AND RESULTS: We studied the risk of stroke in 26 556 male cigarette smokers 50 to 69 years of age without history of stroke. The men were categorized as nondrinkers, light (60 g/d) drinkers. A total of 960 men suffered from incident stroke: 83 with subarachnoid and 95 with intracerebral hemorrhage, 733 with cerebral infarction, and 49 with unspecified stroke. The adjusted relative risk of subarachnoid hemorrhage was 1.0 in light drinkers, 1.3 in moderate drinkers, and 1.6 in heavy drinkers compared with nondrinkers. The respective relative risks of intracerebral hemorrhage were 0.8, 0.6, and 1.8; of cerebral infarction, 0.9, 1.2, and 1.5. Systolic blood pressure attenuated the effect of alcohol consumption in all subtypes of stroke, whereas HDL cholesterol strengthened the effect of alcohol in subarachnoid hemorrhage and cerebral infarction but attenuated the effect in intracerebral hemorrhage. CONCLUSIONS: Alcohol consumption may have a distinct dose-response relationship within each stroke subtype-linear in subarachnoid hemorrhage, U-shaped in intracerebral hemorrhage, and J-shaped in cerebral infarction-but further studies are warranted. Systolic blood pressure and HDL cholesterol seem to mediate the effect of alcohol on stroke incidence, but evidently additional mechanisms are involved.

Economic burden of stroke and the evaluation of new therapies.

Stroke is a major health problem in all industrialised countries and evidence is mounting that this problem also affects the developing countries. In the industrialised countries, it is the third largest killer and, of the survivors, about one-half are left with a permanent handicap. Despite the huge burden of stroke on healthcare and social services (several USA studies estimate the annual cost of stroke to be between US $6.5 and 11.2 billion) the cost of strokes has aroused little attention. An absence of effective therapies may be one of the reasons for this lack of interest; the costs have been taken as inevitable. With the advent of new therapies for acute ischaemic stroke (thrombolytics and neuroprotectants) there is renewed interest in improving both the management and outcome for patients. Key to the evaluation (both clinical and economic) of new stroke therapies is the choice of evaluation scales/instruments. Increasingly, stroke investigators are using measures of functional outcome (for example the Barthel index) as a primary endpoint in stroke trials. This is pertinent, as functional outcome has been found to reflect reasonably well the degree to which a patient needs support after stroke, irrespective of whether this is provided by the family or society.

Prognostic value and determinants of first-day mean arterial pressure in spontaneous supratentorial intracerebral hemorrhage.

BACKGROUND AND PURPOSE: The onset of spontaneous intracerebral hemorrhage (ICH) is often accompanied by transient blood pressure (BP) elevation. The prognostic value and the determinants of this BP reaction have not entirely been solved, and the present study was focused on these questions. METHODS: From 1985 to 1991 in Central Finland (population, 246,000), a total of 425 patients had first-ever ICH verified by CT or necropsy. The hematoma was supratentorial in 337 patients. Of the 306 patients with supratentorial ICH who had CT, 282 had the BP measured at least once within 24 hours of onset, and they formed the study population. The case notes and CT films were reviewed, and mean arterial pressure (MAP) was calculated from the highest BP reading. RESULTS: The fatality rate was high; 43% of the patients were dead within 28 days of onset. Six independent predictors of the 28-day survival were identified by multiple logistic regression; these predictors were consciousness on admission, first-day MAP, subarachnoid spread of the bleed, lateral shift of hemispheral midline structures, admission blood glucose, and vomiting. The MAPs varied between 66.7 and 203.3 mm Hg, and the cutoff points of the MAP quartiles were 118, 132, and 145 mm Hg. Patients in the first three MAP quartiles had relatively fair outcome, with 71%, 65%, and 60%, respectively, alive 28 days after onset. This was in sharp contrast to the fourth quartile, with only 33% surviving the first 28 days (log-rank, P < .0001 to P = .0010). Patients unconscious/ comatose on admission had significantly higher MAPs than did those who were alert or somnolent/disoriented (ANOVA, P = .0079). However, at all levels of consciousness, the 28-day fatality rate increased from the first to the fourth MAP quartile: 69% in the alert, 186% in the somnolent/disoriented, and 45% in the unconscious/comatose patients. Stepwise multiple regression analysis gave four independent predictors of the first-day MAP: hypertension, age (in an inverse fashion), admission blood glucose, and hematoma volume. CONCLUSIONS: The most important predictor of the 28-day survival was the level of consciousness on admission, followed by first-day MAP. Hypertension was the most important predictor of the first-day MAP, followed by age, which had an inverse effect on the MAP level. At all levels of consciousness, high first-day MAP (especially if > 145 mm Hg) worsened the 28-day survival rate.

Decreasing incidence of stroke in central Finland, 1985-1993.

INTRODUCTION: During the last decades the age-standardized stroke mortality has declined in Finland as in many other industrialized countries. Epidemiological studies have, however, not been consistent in explaining this fall in mortality. Our aim was to shed light on this question by using two consecutive, population-based surveys. PATIENTS & METHODS: The target of the two one-year surveys was the population living in the Jyväskylä Region of central Finland, and the surveys were performed in 1985-86 (population 114,669) and 1993 (population 123,547). The case finding methods and the diagnostic criteria were identical in both studies. All hospital records and autopsy reports of patients with ICD (8th and 9th revision) codes 430-438 were collected and perused. Patients with first-ever stroke were included in the study. RESULTS: The number of patients with first-ever stroke in the 1985-86 and 1993 surveys were 219 and 189, respectively, and 92% of them were treated at the Department of Neurology. The age-standardized (European standard population > or = 25 years) annual total stroke incidence showed a statistically significant decline over these 8 years from 317 (95% confidence interval 274-360) to 227 (95% confidence interval 194-260) per 100,000. In both studies the survival was similar with 79% of the patients surviving at 28 days after stroke onset, and 65-69% at 1 year. Recurrent strokes, 52 in 1985-86 and 50 in 1993 also showed a declining trend and no changes in survival were observed. CONCLUSIONS: The decline in stroke mortality in Finland is best explained by the declining incidence of stroke. In the present study we did not find changes in the 1st year survival after stroke onset.

Left ventricular failure and pulmonary edema in acute multiple sclerosis.

We describe a young woman who developed left ventricular failure and pulmonary edema during fulminant onset of multiple sclerosis. One of the numerous plaques was located in the left inferior cerebellar peduncle near the dorsal motor vagal and solitary tract nuclei. Within two days pulmonary edema had cleared, and within three days left ventricular function was normal. To our knowledge, left ventricular failure has not earlier been verified in acute multiple sclerosis.

Factors delaying hospital admission after acute stroke.

BACKGROUND AND PURPOSE: Clinical trials of new drugs that reverse neurological deficits when used in the first hours of stroke onset suggest that early hospital admission is important. We analyzed a database of patients with acute stroke to determine the factors that delay hospital admission. METHODS: We analyzed all patients with their first stroke during 1993 in the province of Central Finland (population, 256 000). Patients referred to the Central Hospital, the only tertiary referral hospital in the area, were included in the study. RESULTS: Of the patients with first stroke, 363 (79%) were admitted to the Central Hospital. The stroke subtype was confirmed in 356 (98%) patients with CT scan, and the patient population included 272 (75%) with brain infarction, 51 (14%) with intracerebral hemorrhage, and 40 (11%) with subarachnoid hemorrhage. The most important factor associated with a delay in reaching the hospital was the referral pattern. The median delay was 2 hours for patients brought directly to the Central Hospital, 8 hours if a physician at the local health center was consulted, and 47 hours if the patient was first admitted to the health center for observation. Other factors associated with a delay were ischemic stroke and stroke onset in the evening or night or during the weekend. CONCLUSIONS: The majority of patients who are candidates for acute stroke trials arrive at the hospital after prolonged delays for multiple reasons. Public and medical personnel education could result in signficant reduction in these delays.

Diurnal blood pressure variations and onset of subarachnoid haemorrhage: a population-based study.

OBJECTIVES: To analyse the association between time of onset of subarachnoid haemorrhage and diurnal blood pressure variations of ambulant normo- and hypertensive subjects. DESIGN: Retrospective, population-based study. SETTING: The population (246,000) of the Health Care District of Central Finland. PATIENTS: During 1980-1987 a total of 332 subjects in the study population had their first subarachnoid haemorrhage. The hour of onset could be obtained for 287 patients, and these form the basis of the present study. RESULTS: The onset of subarachnoid haemorrhage occurred significantly more often during the waking hours than during the night. The correlation between the hourly numbers of patients suffering a haemorrhage and the corresponding mean systolic and diastolic blood pressure values of ambulant normo- and hypertensive subjects was highly significant (r = 0.88, P < 0.001). The results were similar when the 224 patients with proved aneurysmal bleed were analysed separately (r = 0.79-0.85, P < 0.001). CONCLUSIONS: The diurnal blood pressure variations of ambulant normo- and hypertensive subjects, especially the transient blood pressure peaks reaching much higher levels of pressure during the waking hours than during the night, may be crucial in determining the time of rupture of a critically weakened aneurysm wall.