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.

Poststroke depression in acute phase after stroke.

We studied factors associated with acute poststroke depression in 100 patients, aged 27-70, 2 weeks after their first clinically significant stroke. Depressive symptoms were relatively common (27% Beck Depression Inventory > or =10), but the prevalence of major depression was only 5.6%. Older patients were most vulnerable to poststroke depression. Patients with left hemisphere lesion had no more depression than other patients, but when the lesion was in the left hemisphere or in the brainstem, stroke severity was associated with depression.

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.

Nationwide epidemiology of hospitalized patients with first-time traumatic brain injury with special reference to prevention.

The national data of hospitalized TBI-patients were gathered retrospectively during the years 1991-95 from the Hospital Discharge Register. The inclusion criteria were: TBI as the primary diagnosis (ICD-9: 800, 801, 803, 850, 851-854), no history of previous TBI during the previous three years and the hospitalization of the patient. The incidence of TBI varied from 4 793-5 055 (95-100 per 100,000 people), comprising altogether 24,497 patients. The biggest subgroups of external cause were the sudden fall (61%) and vehicle accidents (26%). The biggest subgroups of the place of accident were the home (33%) and the traffic area (30%). The data reflect an assumption that many causes of TBI are preventable.

Masticatory force and function in patients with hemispheric brain infarction and hemiplegia.

Recent functional animal studies have reported that the motor control of masticatory muscle function is bilaterally guided by both hemispheres, which may fundamentally differ from the cortical control of limb muscle function. In this study, we investigated whether unilateral cortical brain infarction induces different impairments in masticatory and upper limb motor performance. Evidence of the importance of both hemispheres in controlling masticatory movements would be greater if the masticatory function were shown to be unimpaired in patients with severe hemiplegia. The masticatory function of 16 patients with severe hemiparesis caused by brain infarction in the region of the middle cerebral artery was studied by means of interview, clinical examination, and bite-force measurements. Finger-thumb grip-force measurements and clinical examination of the upper limbs were also performed for evaluation of the effect of infarction on upper limb motor function. Localization of the infarction was confirmed with computer tomography and magnetic resonance imaging. The Scandinavian Stroke Scale demonstrated that each patient had a major unilateral cortical infarction which had caused a marked handicap with a serious impairment of upper limb function on the contralateral side. The clinical examination revealed no major signs of temporomandibular disorders, and the masticatory muscles, when examined by palpation, contracted symmetrically. None of the patients with unilateral brain infarction showed any differences in bite forces between the healthy and paralyzed sides. These results indicate that, in hemiparetic patients, great differences may exist between the motor performances of the masticatory and upper limb muscles. The present investigation clinically illustrates the importance of both hemispheres in the control of masticatory function and movements.

Prevention of poststroke depression: 1 year randomised placebo controlled double blind trial of mianserin with 6 month follow up after therapy.

OBJECTIVES: (1) To test whether early prophylactic antidepressive treatment by mianserin is able to prevent poststroke depression, and (2) to discover whether mianserin as an antidepressant has any beneficial influence on the outcome of ischaemic stroke. METHODS: A randomised, double blind, placebo controlled study involved 100 consecutive patients under 71 years old admitted to hospital for an acute ischaemic stroke; they were enrolled to receive 60 mg/day mianserin or placebo for 1 year. They were examined on admission, and at 2, 6, 12, and 18 months with depression, stroke, and functional outcome scales. RESULTS: According to DSM-III-R, the prevalence of major depression was 6% at the initial stage, 11% at 1 year, and 16% at 18 months. At no time point did prevalences differ between the treatment groups, nor were differences found in depression scales, although at 2 months a greater improvement from initial assessment on the Hamilton depression scale was evident in patients on mianserin (p=0.05). Some beneficial changes on the Hamilton depression scale and Beck depression inventory were found in patients older than 56 (median age) and in men treated with mianserin, but not in other subgroups. Mianserin treatment did not affect stroke outcome as measured by neurological status, nor did it have any influence on functional outcome as measured by Rankin scale or Barthel index. CONCLUSION: It was not possible to show that early initiation of antidepressant therapy can prevent poststroke depression, because the prevalence of poststroke depression remained low even in patients on placebo. In this stroke population with a low rate of depressive patients, antidepressive medical treatment failed to affect stroke outcome.

Genetic polymorphism of platelet glycoprotein IIIa in patients with acute myocardial infarction and acute ischaemic stroke.

BACKGROUND: It has recently been suggested that the Leu33Pro polymorphism of the platelet glycoprotein IIIa affects the risk of coronary thrombosis. Finland is genetically isolated and has an incidence of cardiovascular disease among the highest in the world. Interestingly, the prevalence of ischaemic heart disease also varies in different parts of the country, being highest in eastern Finland. METHOD: We studied the Leu33Pro polymorphism using polymerase chain reaction in 133 patients with coronary artery disease, 234 patients with cerebrovascular disease and 326 control subjects originating from two areas of Finland. RESULTS: The frequencies of the Pro33 allele in the patients with acute myocardial infarction and cerebrovascular attack were 13% and 14%, respectively, and did not differ from the controls (13%). Among patients with acute myocardial infarction from the Helsinki area, the family history of premature coronary artery disease was more often positive in carriers of the Pro33 allele than in non-carriers, but after adjustment for multiple comparisons the difference was no longer significant. CONCLUSIONS: We could not confirm the original observation that the Pro33 allele constitutes an independent risk factor for coronary artery disease. Further studies are needed to clarify whether co-occurrence of Pro33 and some unrecognized inherited factor pose an additional risk of vascular disease.

Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme.

DNA polymorphisms in genes encoding apolipoproteins (apo) A-I, C-III, B and E and angiotensin-converting enzyme (ACE) have been proposed to be associated with the risk of coronary artery disease (CAD). We studied whether the same genetic markers would also be associated with the occurrence and extent of atherosclerosis in cervical arteries. DNA samples from 234 survivors of stroke or a transient ischaemic attack aged 60 years or less were examined. The presence of atherosclerosis was assessed using aortic arch angiograms. The SstI polymorphism of apoA-I/C-III gene locus, the XbaI polymorphism of apoB gene, common apoE phenotypes and the insertion/deletion polymorphism of the ACE gene were analysed. The allele frequencies of the apoA-I/C-III, apoB, apoE or ACE gene did not differ between the groups with (n = 148) or without (n = 85) cervical atherosclerosis. However, when patients with at least one apoE4 allele and one X2 allele of apoB were combined and compared with those without either of them (E2E3 or E3E3 and X1X1), a significant association with the presence of cervical atherosclerosis was found (P = 0.03). The patients having the E2E3 phenotype had a significantly elevated serum triglyceride level compared with those with the E3E3 phenotype (P = 0.03). Serum high-density lipoprotein (HDL) cholesterol was lower in the patients with the E2E3 phenotype than in those with the E3E3 and E3E4 (P = 0.01 and P = 0.06, respectively). The apoB or ACE genotypes were not significantly associated with serum lipid or lipoprotein levels. There was no association between the ACE gene polymorphism and the occurrence of hypertension. In conclusion, the interaction of common apoB and apoE alleles may increase the risk of atherosclerosis in cervical arteries.

Risk factors for spontaneous intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage has remained a serious disease despite recent improvements in medical treatment. This study was designed to identify modifiable risk factors for intracerebral hemorrhage. METHODS: Health habits, previous diseases, and medication of 156 consecutive patients with intracerebral hemorrhage aged 16 to 60 years (96 men and 60 women) were compared with those of 332 hospitalized control patients (192 men and 140 women) who did not differ from case subjects in respect to age, day of onset of symptoms, or acuteness of disease onset. RESULTS: After adjustment for sex, age, hypertension, body mass index, smoking status, and alcohol consumption during the last week, patients who had consumed 1 to 40, 41 to 120, or > 120 g of alcohol within the 24 hours preceding the onset of illness had a relative risk (95% confidence interval) of hemorrhage of 0.3 (0.2 to 0.7), 4.6 (2.2 to 9.4), and 11.3 (3.0 to 42.8), respectively, compared with those who had consumed 0 g. In addition, alcohol intake within 1 week before the onset of illness, excluding use within the last 24 hours, increased the risk of hemorrhage; adjusted risks were 2.0 (1.1 to 3.5) for 1 to 150 g, 4.3 (1.6 to 11.7) for 151 to 300 g, and 6.5 (2.4 to 17.7) for > 300 g compared with 0 g. The adjusted risk of hypertension for hemorrhage was 6.6 (3.9 to 11.3). Previous heavy alcohol consumption and current cigarette smoking were not independent risk factors for hemorrhage, but anticoagulant treatment was (P < .01). Erythrocyte mean corpuscular volume and gamma-glutamyl transferase values were also higher in patients with intracerebral hemorrhage than in control subjects. CONCLUSIONS: Recent moderate and heavy alcohol intake as well as hypertension and likely also anticoagulant treatment seem to be independent risk factors for intracerebral hemorrhage.

Arg506Gln factor V mutation (factor V Leiden) in patients with ischaemic cerebrovascular disease and survivors of myocardial infarction.

The point mutation Arg506- > Gln of factor V was recently shown to be an important and relatively common genetic cause of venous thromboembolism. Using a DNA technique based on polymerase chain reaction, we surveyed the blood samples of 236 patients with ischaemic stroke or a transient ischaemic attack, 122 survivors of myocardial infarction and 137 control subjects for the presence of this mutation. Although the frequency of the factor V mutation in patients with arterial disease (4.5%) was not significantly different from that in healthy blood donors (2.9%), a carrier status for this mutant gene was associated with symptoms of migraine and relatively mild angiographic abnormalities among patients with cerebrovascular disease. A more extensive study addressing the occurrence and significance of the mutant factor V mutation in patients with vasospastic cerebrovascular diseases seems to be warranted.

Where and how should elderly stroke patients be treated? A randomized trial.

BACKGROUND AND PURPOSE: Elderly stroke patients in particular are at risk of receiving less than optimal care. We studied the effects of the department care (medicine versus neurology) on the outcome of elderly stroke patients in a randomized controlled trial with 1-year follow-up. METHODS: A total of 243 consecutive patients aged 65 years or older with acute stroke were randomized to receive care in the Departments of Medicine or the Department of Neurology of a university teaching hospital with a referral area of 1.1 million. The outcome was assessed by mortality, length of hospital stay, ability to live at home on discharge, Barthel Index, and Rankin grades at 1 year. RESULTS: There were no differences in sex and age, severity or type of stroke, other diseases, or social factors between the two groups. One-year mortality was 21% in both patients treated by the Departments of Medicine and those treated by the Department of Neurology. Patients treated by the Department of Neurology were discharged an average of 16 days earlier (24 versus 40 days). The length of hospital stay of patients aged younger than 75 years differed significantly (P = .02). Patients randomized to neurological wards more often went directly home (75% versus 62%; P = .03), and their functional status was better as assessed with Barthel Index and Rankin grades at 1 year (P = .02 and P = .03, respectively). Independent predictors of a better functional outcome and shorter hospital stay by stepwise multivariate analysis included management by the Department of Neurology. CONCLUSIONS: Well-organized management of elderly stroke patients was associated with a better outcome. It was also the more economical alternative.

Recent alcohol consumption, cigarette smoking, and cerebral infarction in young adults.

BACKGROUND AND PURPOSE: The role of recent heavy drinking of alcohol as a risk factor for ischemic brain infarction is unclear. We investigated this problem in young adults, in whom even a thorough workup often fails to reveal any predisposing factor. METHODS: This was a hospital-based case-control study comprising 75 consecutive subjects aged 16 to 40 years with first-ever ischemic brain infarction and 133 control subjects from the same hospital who were group-matched with the case patients for age, sex, day of the onset of symptoms, and acuteness of disease onset. RESULTS: Multiple logistic regression analysis showed that alcohol intake exceeding 40 g of ethanol within the 24 hours preceding disease onset was a significant independent risk factor for brain infarction among both men (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.8 to 20.3) and women (OR, 7.8; 95% CI, 1.0 to 60.8). Cigarette smoking was not found to be an independent risk factor in the model, whereas among men arterial hypertension was (OR, 6.2; 95% CI, 1.5 to 24.7). CONCLUSIONS: We conclude that very recent alcohol drinking, particularly drinking for intoxication, may trigger the onset of brain infarction in young adults and that there might be a variety of mechanisms behind this effect.

A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke.

BACKGROUND AND PURPOSE: A randomized, double-blind, placebo-controlled multicenter trial was conducted to test the hypothesis that nimodipine would improve the functional outcome in acute ischemic hemispheric stroke. METHODS: A total of 350 patients were randomized to nimodipine 120 mg/d PO or matching placebo for 21 days. Randomization was stratified by onset of therapy, age, and stroke severity. Treatment was begun within 48 hours of onset. The patients had neurological evaluation on admission, on days 1, 7, and 21, and at 3 and 12 months. The primary end points were Rankin grade, neurological score, and mobility at 12 months. RESULTS: We did not find any differences in the functional outcome between the treatment groups or between the stratified subgroups. We were also unable in post hoc analyses to find any groups of patients who benefited from nimodipine. During the first month and at 3 months the case-fatality rate was higher in the nimodipine-treated patients than in those on placebo (P = .004 and P = .030, respectively), but at the 1-year follow-up this difference had lost statistical significance. During the first week nimodipine had a statistically significant lowering effect on both systolic (P = .005) and diastolic (P = .013) blood pressure. CONCLUSIONS: Nimodipine did not improve the functional outcome of acute ischemic hemispheric stroke. The early case-fatality rate was higher in the nimodipine group, possibly due to the blood pressure-lowering effect of nimodipine.

Regular light-to-moderate intake of alcohol and the risk of ischemic stroke. Is there a beneficial effect?

BACKGROUND AND PURPOSE: To evaluate the association between different patterns of alcohol consumption and the risk of ischemic stroke in young or middle-aged men. METHODS: One hundred fifty-six patients and 153 control subjects were included in this case-control study. The pattern and the estimated average weekly intake of alcohol were assessed using a structured questionnaire. The pattern of drinking was defined as regular (daily or almost daily) or irregular (up to three times per week), and the weekly amount of consumption was defined as nondrinking, light-to-moderate drinking (up to 150 g/wk), moderate drinking (> 150 to 300 g/wk), and heavy drinking (> 300 g/wk). Multiple stepwise logistic regression models were used, and adjustments were carried out for potential confounders. RESULTS: Heavy alcohol intake associated with an increased risk of stroke (odds ratio, 4.45; 95% confidence interval, 1.09 to 18.1), whereas the risk tended to be reduced in light-to-moderate drinkers (odds ratio, 0.54; 95% confidence interval, 0.28 to 1.05). Accounting for the pattern of alcohol intake in addition to the average weekly amount in grams, regular light-to-moderate drinking showed a significant inverse association with stroke (odds ratio, 0.12; 95% confidence interval, 0.02 to 0.65), and an irregular pattern of consumption attenuated this association. Based on the same multivariate analyses, other significant independent risk factors for stroke were arterial hypertension, coronary heart disease, and history of snoring, whereas the contributions of age, diabetes mellitus, smoking, and body mass index proved to be nonsignificant. CONCLUSIONS: Light-to-moderate alcohol intake appears to have an inverse association with the risk of ischemic stroke. The beneficial effect appears to be most prominent if the consumption of alcohol is regular and evenly distributed throughout the week, whereas a sporadic or an occasional pattern of drinking seems to weaken the association. This study also supports the role of heavy drinking as an independent risk factor for ischemic stroke.

Risk factors for cervical atherosclerosis in patients with transient ischemic attack or minor ischemic stroke.

BACKGROUND AND PURPOSE: Our purpose was to study potential determinants of the presence and the severity of cervical atherosclerosis in patients with transient ischemic attack or minor ischemic stroke. METHODS: Two hundred ninety-four patients up to 60 years of age were included in this cross-sectional study. The male to female ratio was 171/123. Atherosclerosis was defined as the presence of any visible atherosclerotic lesion in anteroposterior or left oblique views of cervical arteries in aortic arch angiograms. The severity of atherosclerosis was assessed using three scores, which were computed separately for the total thickness and length of all plaques as well as for the percent stenosis of the vessels. RESULTS: Atherosclerosis was present in 180 patients (61.2%). In a multiple stepwise logistic regression analysis, age, serum triglycerides, smoking history for more than 20 years, arterial hypertension (defined as systolic or diastolic blood pressure values at least 150 or 100 mm Hg, respectively, or the use of antihypertensive medication), regular light alcohol consumption (inversely), and body mass index (marginal inverse association) were independent determinants of the presence of atherosclerosis; the respective odds ratios were 1.1/1 y, 1.8/1 mmol/L, 3.3, 2.4, 0.3, and 0.9/1 kg/m2. In multiple linear regression models, age was associated positively and the ratio of high density lipoprotein to total cholesterol was associated negatively with the severity of atherosclerosis regardless of the scoring method, whereas current smoking and female sex were predictors only of the percent stenosis and the length of the lesions. Arterial hypertension showed a significant association only with the length of the lesions. CONCLUSIONS: Age, cigarette smoking, and arterial hypertension contribute substantially to atherosclerosis in cervical arteries, but this study also confirms the independent associations of lipid or lipoprotein variables with atherosclerotic disease. An independent inverse association of regular light consumption of alcohol with cervical atherosclerosis was also observed.

Association of thromboxane B2 production to hypoxemic periods during sleep in male stroke patients.

To evaluate the possible association between sleep apneas and platelet function, we recorded sleep-related hypoxemic periods and measured platelet thromboxane B2 release in 10 male patients with a previous brain infarction. Four of them revealed an increased morning release of thromboxane B2 compared with the night before, whereas six had an opposite situation. Those with an increased morning release revealed more hypoxemic episodes during the night than the others (median numbers were 58.5 and 2, respectively; p = 0.031), suggesting that sleep apneas may influence platelet function among male stroke victims. This finding might be involved in the suggested role of obstructive sleep apnea syndrome as a risk factor for ischemic stroke as well as the peaking of ischemic strokes in the early morning hours.

Snoring, sleep apnea syndrome, and stroke.

Increasing evidence suggests that snoring and sleep apnea are associated with cerebrovascular diseases. Several other factors may be involved in this association because many established or potential risk factors for stroke are related to snoring and sleep apnea. These include arterial hypertension, coronary heart disease, age, obesity, smoking, and alcohol consumption. Recent epidemiologic and clinical studies indicate, however, that snoring can increase the risk of stroke independently of these confounding factors. Accumulating epidemiologic evidence of long-term harmful effects of the obstructive sleep apnea syndrome appears to be related to increasing vascular morbidity and mortality. Potential mediators among snoring, obstructive sleep apneas, and stroke include cardiac arrhythmias and other hemodynamic disturbances, increased levels of catecholamines, and disturbances in cerebral blood flow caused by sleep apneas, as well as hypoxemic periods that may potentiate atherosclerosis.

Snoring and the risk of ischemic brain infarction.

To determine if a history of snoring is a risk factor for brain infarction, I conducted a case-control study of risk factors for ischemic stroke using 177 consecutive male patients aged 16-60 (mean 49) years with acute brain infarction. For each patient I chose an age-matched (+/- 6 years) male control. Arterial hypertension, coronary heart disease, snoring (habitually or often), and heavy drinking (greater than 300 g/wk) were risk factors in the stepwise multiple logistic regression analysis. The odds ratio of snoring for brain infarction was 2.13. By McNemar's test this association increased strongly if a history of sleep apnea, excessive daytime sleepiness, and obesity were all present with snoring (odds ratio 8.00). My study indicates that snoring may be a risk factor for ischemic stroke, possibly because of the higher prevalence of an obstructive sleep apnea syndrome among snorers than nonsnorers.

Snoring as a risk factor for sleep-related brain infarction.

We studied 177 consecutive male patients aged 16-60 years with brain infarction verified by neuroradiology and analyzed the time of onset of stroke symptoms related to sleep and the role of possible or known risk factors for brain infarction. Brain infarction occurred relatively more often during the first 30 minutes after awakening than at any other time. In multiple stepwise logistic regression analyses, snoring was the only independent risk factor differentiating stroke occurring during sleep and stroke occurring either during sleep or during the first 30 minutes after awakening from stroke occurring at other times of the day. The risk ratios were 2.65 (95% confidence interval 1.32-5.29, p less than 0.005) and 3.16 (95% confidence interval 1.61-6.22, p less than 0.001), respectively. Other factors tested were age, arterial hypertension, diabetes mellitus, smoking, alcohol consumption, and body mass index. Arterial hypertension seemed to have an additive effect on the independent risk caused by snoring.