Early vs. late enoxaparin for the prevention of venous thromboembolism in patients with ICH: A double blind placebo controlled multicenter study.

BACKROUND: Venous thromboembolism (VTE) after primary intracerebral hemorrhage (ICH) worsens patient prognosis. Administering low-molecular weight heparins (LMWH) to prevent VTE early (24 h) may increase the risk of hematoma enlargement, whereas administering late (72 h) after onset may decrease its effect on VTE prevention. The authors investigated when it is safe and effective to start LMWH in ICH patients. METHODS: In the setting of double blinded, placebo controlled randomization, patients >18 years of age with paretic lower extremity, and admitted to the emergency room within 12 h of the onset of ICH, were randomized into two groups. Patients in the enoxaparin group received 20 mg twice a day 24 h (early) after the onset of ICH and in the placebo group 72 h (late) after onset respectively. Both groups immediately received intermittent pneumatic compression stockings at the ER. Patients were prospectively and routinely screened for VTE and hemorrhagic complications 1 day after entering the study and again before discharge. RESULTS: 139 patients were included for randomization in this study. Only 3 patients developed VTE, 2 in the early enoxaparin group and one in the late enoxaparin group. No patients developed PE. Thromboembolic events (p = 0.901), risk of hematoma enlargement (p = 0.927) and overall outcome (P = 0.904) did not differ significantly between the groups. CONCLUSION: Administering 40 mg/d LMWH for prevention of VTE to a spontaneous ICH patient is safe regardless of whether it is started 24 h (early) or 72 h (late) after the hemorrhage. Risk of hemorrhage enlargement is not associated with early LMWH treatment. Administering LMWH late did not increase VTEs.

Mortality of subjects with alcohol-related seizures increased after alcohol cheapening.

OBJECTIVE: To investigate whether the reduction of alcohol prices in Finland (March 1, 2004) associated with an increase in mortality of subjects with alcohol-related seizures. PATIENTS AND METHODS: All subjects with head trauma in Oulu University Hospital during 1999 (n = 827) were identified and thereafter followed up until death or the end of 2009. We used National Hospital Discharge Register, hospital charts, and death records from Official Cause-of-Death Statistics to identify seizure visits and alcohol-related deaths. Kaplan-Meier survival curves were used to characterize the effect of alcohol price reduction on risk of death. Cox proportional hazards model was used to identify independent predictors of death. RESULTS: Twenty-five subjects had alcohol-related seizures before the alcohol price reduction. Their cumulative mortality rate was significantly higher (P = 0.015) than that of other head trauma subjects during the follow-up and it clearly increased after the price reduction. Age (HR 1.06 per year, 95% CI 1.05-1.07, P < 0.001), moderate-to-severe traumatic brain injury (HR 2.04 95% CI 1.37-3.04, P < 0.001), and alcohol-related seizure (HR 3.02, 95% CI 1.48-6.16, P = 0.002) were independent predictors of death after adjustment for confounding factors. CONCLUSION: We conclude that the political decision to lower alcohol price associated with a significant increase in the mortality rate of subjects with alcohol-related seizures.

Head trauma sustained under the influence of alcohol is a predictor for future traumatic brain injury: a long-term follow-up study.

BACKGROUND AND PURPOSE: Hazardous drinking may result in recurrent head trauma. It was investigated whether head trauma sustained under the influence of alcohol is a predictor of future traumatic brain injury (TBI). METHODS: All subjects with head trauma (n = 827) brought to the emergency room at Oulu University Hospital during 1999 were identified and followed up until death or the end of 2009. The National Hospital Discharge Register and hospital charts were used to identify TBIs during the follow-up and Kaplan-Meier curves and the Cox proportional hazards model were used to characterize predictors of TBI. RESULTS: During the total follow-up of 7386 person-years, 52/827 subjects sustained a new head trauma with TBI and the risk of TBI was significantly (P = 0.005) higher amongst subjects who had been under the influence of alcohol at the time of the index trauma in 1999. New TBI occurred under the influence of alcohol in 30/52 cases (57.7%). An alcohol-related index trauma [adjusted hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.38-4.56, P < 0.01] and history of TBI (HR 3.39, 95% CI 1.32-8.72, P < 0.05) were independent risk factors for subsequent TBI after adjustment for sex and age. A history of harmful drinking was also a significant risk factor (adjusted HR 10.37, 95% CI 5.53-19.43, P < 0.001). In the subset of 396 patients having an index head trauma without TBI, this being alcohol related was also a significant risk factor for subsequent TBI after adjustment for sex, age and history of TBI (HR 3.54, 95% CI 1.36-9.18, P = 0.009). CONCLUSIONS: Even head trauma without TBI under the influence of alcohol implies an elevated risk of subsequent TBI. A brief intervention to reduce hazardous drinking is needed to prevent TBI.

Health-related quality of life and cost-effectiveness of treatment in subarachnoid haemorrhage.

BACKGROUND: Treatment of aneurysmal subarachnoid haemorrhage (SAH) demands high healthcare resource utilization. Case fatality and disability remain as common outcomes of SAH. The purpose of this study was to perform a treatment cost-effectiveness analysis of patients with SAH. METHODS: We performed a long-term follow-up of the SAH patients treated in our institution over a 3-year period starting February 1998. Outcome 10 years after the SAH and treatment costs were evaluated. The health-related quality of life was evaluated using the EuroQol (EQ-5D) questionnaire and visual-analogue scale (VAS). The cost of a quality-adjusted life year (QALY) was calculated. RESULTS: Median follow-up time of the 178 patients was 10.8 years. Overall mortality rate was 24%. Of the 43 non-survivors, 42% died within 6 months. For the 135 survivors, the median EQ-5D index value was 1.00, which is similar to that for normal population. The median VAS value was 80, which is comparable to normal population's value. Of the survivors, 88% (119/135) were able to live at home and 63% (85/135) returned to work after SAH. The cost of neurosurgical treatment for one QALY was 1700€. CONCLUSION: Long-term outcome of survivors after aneurysmal SAH was relatively good: most of them lived at home, 63% had returned to work and 36% were still working. The quality of life index of the survivors was similar to that of normal populations, and the survivors were as satisfied with their health as people in general are. Cost of neurosurgical treatment and cost of a QALY gained were acceptable.

Early cerebral infarction as a risk factor for poor outcome after aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: After aneurysmal subarachnoid haemorrhage, severity of bleeding, and occurrence of rebleeding and cerebral infarcts are the main factors predicting outcome. We investigated predictive risk factors for both early and late cerebral infarcts, and whether time of appearance of infarct is associated with outcome. METHODS: Previous diseases as well as clinical, laboratory and radiological variables including serial CT scans were recorded for 173 patients admitted within 48 h after bleeding and with ruptured aneurysm occlusion by open surgery within 60 h. Factors predicting occurrence of cerebral infarct and poor outcome at 3 months according to the Glasgow Outcome Scale were tested using multiple logistic regression. RESULTS: Of several potential predictors, poor outcome was independently predicted by patient age, rebleeding, intraventricular haemorrhage, intracerebral haematoma, delayed cerebral ischaemia with fixed symptoms and early new ischaemic lesion on CT scan appearing on the 1st post-operative morning (P<0.01 for each factor). After adjustment for confounding factors, occurrence of early infarct (odds ratio 12.5; 95% confidence interval 3.2-48.7; P<0.01), both early and late infarct (6.6; 1.1-40.4; P<0.05), and late infarct only (2.4; 0.6-9.1) increased risk for poor outcome. Adjusted independent significant risk factors for early infarction were duration of artery occlusion during surgery (1.4/min; 1.1-1.7, P<0.01) and admission plasma glucose level (1.3 per mM; 1.0-1.6, P<0.05) and for late infarction amount of subarachnoid blood (4.5; 1.3-14.9, P<0.05). CONCLUSION: Early infarction after surgical aneurysm occlusion seems to have different risk factors and worse prognosis than late infarct which is mostly associated with delayed cerebral ischaemia.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review.

OBJECTIVES: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. METHODS: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. RESULTS: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). CONCLUSIONS: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome.

Better than expected survival after primary intracerebral hemorrhage in patients with untreated hypertension despite high admission blood pressures.

BACKGROUND: Hypertension is the most important modifiable risk factor for primary intracerebral hemorrhage (ICH), but little is known of the effect of preceding hypertension on outcome. Because high mean arterial blood pressure (MABP) at admission is an independent predictor of early death in patients with ICH, we explored its role on survival and poor outcome separately in normotensive subjects and subjects with treated and untreated hypertension. METHODS: We assessed clinical data and the 3-month outcome of patients with spontaneous ICH (n = 453) admitted to the stroke unit of Oulu University Hospital between 1993 and 2004. Standard medical treatment was used to lower MABP from levels >127 mmHg to <120 mmHg. RESULTS: Overall mortality within 3 months was 28%. Patients with untreated hypertension had significantly lower mortality (6%) than those with treated hypertension (36%, P < 0.001) or those without hypertension (25%, P < 0.01). High admission MABP associated with early death in normotensive subjects (P < 0.05) and those on medication for hypertension (P < 0.01) but not in those with untreated hypertension. Patients with untreated hypertension were younger and had less frequently cardiac disease, diabetes, and/or warfarin or aspirin medications, but they showed the highest blood pressures (BPs) at admission. Amongst patients with high admission MABP, favorable outcome was seen most frequently in those who had untreated hypertension. Hematoma growth did not associate with high MABP amongst them. CONCLUSION: Despite their higher BP values at admission, subjects with untreated hypertension showed better survival and more frequently favorable outcome after BP-lowering therapy than other patients.

Natural history of unruptured intracranial aneurysms: risks for aneurysm formation, growth, and rupture.

Several studies concerning risk factors for SAH and for subsequent rupture of an unruptured aneurysm have been published, but not risk factor studies for formation and growth rate of aneurysms. Because less than half of all aneurysms ever rupture, it is essential to know risk factors separately both for aneurysm formation and for its growth. Before 1979, unruptured aneurysms were not operated on in Helsinki. Recently, the results of risk factors for rupture of unruptured aneurysms of 142 patients (131 with a prior SAH) have been published. 89 were followed with conventional and/or 3D CT angiography, or at autopsy to define risk factors for aneurysm formation and growth. During 2575 person-years, 33 of the 142 patients (23%) suffered SAH, resulting in an annual incidence of 1.3% (95% CI, 0.9-1.7%). The cumulative rate of bleeding was 10.5% (95% CI, 5.3-15.8%) at 10 years, and 30.3% (21.1-39.6%) at 30 years. Independent risk factors for rupture were cigarette smoking (time-dependent relative risk, 3.04; 95% CI, 1.21-7.66), and size of aneurysm (1.14 per mm; 1.01-1.30) after adjustment for age, aneurysm group, and hypertension. In addition, current cigarette smoking at end of follow-up (age-adjusted odds ratio, 3.92; 95% CI, 1.29-11.93) and female gender 3.36 (1.11-10.22) were the only independent risk factors for aneurysm growth of > or = 1 mm but only current smoking (3.48, 1.14-10.64) was a risk factor for growth of > or = 3 mm. Probability of de novo aneurysm formation was 0.84% per year (95% CI, 0.47-1.37%). Female gender (adjusted odds ratio, 4.73; 95% CI, 1.16-19.38) and current smoking (4.07, 1.09-15.15) were the only significant (p < 0.05) independent risk factors for de novo aneurysm formation. Cessation of smoking is very important for these patients. It is recommended that unruptured aneurysms be operated on irrespective of their size and of patients' smoking status, in people aged < 50 to 60 years.

Use of aspirin, epistaxis, and untreated hypertension as risk factors for primary intracerebral hemorrhage in middle-aged and elderly people.

BACKGROUND AND PURPOSE: The incidence of primary intracerebral hemorrhage (ICH) increases exponentially with age, but the risk factors are not well known. We investigated lifestyle factors, previous diseases, and medications as risk factors for ICH in middle-aged and elderly people. METHODS: We compared 98 consecutive patients with primary ICH between 36 and 90 years of age with 206 community-based control subjects matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for possible confounding variables were calculated by logistic regression. RESULTS: The independent risk factors for ICH were untreated hypertension (OR, 6.95; 95% CI, 3.06 to 15.8), previous ischemic stroke (OR, 3.83; 95% CI, 1.70 to 8.63), epilepsy (OR, 13.8; 95% CI, 2.49 to 76.6), recent strenuous physical exertion (OR, 3.97; 95% CI, 1.95 to 8.10), and a history of epistaxis (OR, 2.92; 95% CI, 1.28 to 6.62). In men, treated hypertension (OR, 2.67; 95% CI, 1.03 to 6.93) was also a significant risk factor. Patients with a history of epistaxis who had used nonsteroidal anti-inflammatory drugs, especially aspirin in high doses, had an increased risk for ICH (adjusted OR of epistaxis, 2.75; 95% CI, 1.11 to 6.81; adjusted OR of aspirin use, 14.7; 95% CI, 2.03 to 106). In addition, there was a significant (P:<0.01) positive interaction between the history of epistaxis and the use of aspirin on the risk for ICH. CONCLUSIONS: Epistaxis is a risk factor for ICH in middle-aged and elderly people, both independently and combined with the use of aspirin. Other independent risk factors are untreated hypertension, previous ischemic stroke, epilepsy, and recent strenuous physical exertion. Epistaxis may be a warning sign of an increased risk for ICH in subjects using aspirin.

Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study.

BACKGROUND AND PURPOSE: We sought to investigate factors determining growth rate of unruptured intracranial aneurysms as well as formation of new (de novo) aneurysms in patients from a time period when unruptured aneurysms were not treated surgically. METHODS: Eighty-seven patients (79 had ruptured aneurysms clipped at start of follow-up) with 111 unruptured aneurysms as well as an additional 7 patients (2 with and 5 without unruptured aneurysms) who developed new aneurysms were followed from the 1950s to the 1970s until death or subarachnoid hemorrhage or until the last contact. Patients' cerebral arteries were examined later either with conventional (control) angiography (n=38) and/or, for those alive during 1996-1998, with 3-dimensional CT angiography (n=57). In addition, 10 patients were studied at neuropathological autopsy. RESULTS: Mean+/-SD duration of follow-up was 18.9+/-9.4 years (range, 1.2 to 38.9 years). Unruptured aneurysms increased in size >/=1 mm in 39 of the 87 patients (45%) and >/=3 mm in 31 (36%). New aneurysms were found in 15 of the 89 patients and in 5 without an unruptured aneurysm at the beginning of follow-up. Aneurysm rupture was associated very significantly (P:<0.001) with aneurysm growth during follow-up. Of several potential risk factors tested, only cigarette smoking (odds ratio [OR], 3.92; 95% CI, 1.29 to 11.93) and female sex (OR, 3.36; 95% CI, 1.11 to 10.22) were, after adjustment for age, significant (P:<0.05) independent risk factors for occurrence of aneurysm growth of >/=1 mm. Only cigarette smoking (OR, 3.48; 95% CI, 1.14 to 10.64; P:<0.05) was associated with growth of >/=3 mm. Age- and hypertension-adjusted risk factors for aneurysm formation were female sex (OR, 4.73; 95% CI, 1.16 to 19.38) and cigarette smoking (OR, 4.07; 95% CI, 1.09 to 15.15). CONCLUSIONS: Women and cigarette smokers are at increased risk for intracranial aneurysm formation and growth. Cigarette smoking in particular hastens aneurysm growth. Cessation of smoking is important for patients with unruptured aneurysms and possibly also for those with a prior subarachnoid hemorrhage.

Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture.

OBJECT: The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed. METHODS: One hundred forty-two patients with 181 unruptured aneurysms were followed from the 1950s until death or the occurrence of subarachnoid hemorrhage or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using lifetable analyses and Cox's proportional hazards regression models including time-dependent covariates. The median follow-up time was 19.7 years (range 0.8-38.9 years). During 2575 person-years of follow up, there were 33 first-time episodes of hemorrhage from previously unruptured aneurysms, for an average annual incidence of 1.3%. In 17 patients, hemorrhage led to death. The cumulative rate of bleeding was 10.5% at 10 years, 23% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm (relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1-1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93-1, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04-2.06, p = 0.033) after adjustment for size of the aneurysm, patient age, sex, presence of hypertension, and aneurysm group. Active smoking status as a time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21-7.66, p = 0.02). CONCLUSIONS: Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated regardless of their size and of a patient's smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage.

OBJECT: The pathogenesis of cerebral vasospasm and delayed ischemia after subarachnoid hemorrhage (SAH) seems to be complex. An important mediator of chronic vasospasm may be endothelin (ET), with its powerful and long-lasting vasoconstricting activity. In this study the author investigated the correlation between serial plasma concentrations of ET and ischemic symptoms, angiographically demonstrated evidence of vasospasm, and computerized tomography (CT) findings after aneurysmal SAH. METHODS: Endothelin-1 immunoreactivity in plasma was studied in 70 patients with aneurysmal SAH and in 25 healthy volunteers by using a double-antibody sandwich-enzyme immunoassay (immunometric) technique. On the whole, mean plasma ET concentrations in patients with SAH (mean +/- standard error of mean, 2.1 +/- 0.1 pg/ml) did not differ from those of healthy volunteers (1.9 +/- 0.2 pg/ml). Endothelin concentrations were significantly higher (p < 0.05) in patients who experienced delayed cerebral ischemia with fixed neurological deficits compared with those in other patients (post-SAH Days 0-5, 3.1 +/- 0.8 pg/ml compared with 2.1 +/- 0.2 pg/ml; post-SAH Days 6-14, 2.5 +/- 0.4 pg/ml compared with 1.9 +/- 0.2 pg/ml). Patients with angiographic evidence of severe vasospasm also had significantly (p < 0.05) elevated ET concentrations (post-SAH Days 0-5, 3.2 +/- 0.8 pg/ml; post-SAH Days 6-14, 2.7 +/- 0.5 pg/ml) as did those with a cerebral infarction larger than a lacuna on the follow-up CT scan (post-SAH Days 0-5, 3.1 +/- 0.8 pg/ml; post-SAH Days 6-14, 2.5 +/- 0.4 pg/ml) compared with other patients. Patients in whom angiography revealed diffuse moderate-to-severe vasospasm had significantly (p < 0.05) higher ET levels than other patients within 24 hours before or after angiography (2.6 +/- 0.3 compared with 1.9 +/- 0.2 pg/ml). In addition, patients with a history of hypertension or cigarette smoking experienced cerebral infarctions significantly more often than other patients, although angiography did not demonstrate severe or diffuse vasospasm more often in these patients than in others. CONCLUSIONS: Endothelin concentrations seem to correlate with delayed cerebral ischemia and vasospasm after SAH. The highest levels of ET are predictive of the symptoms of cerebral ischemia and vasospasm, and ET may also worsen ischemia in patients with a history of hypertension. Thus, ET may be an important causal or contributing factor to vasospasm, but its significance in the pathogenesis of vasospasm remains unknown.

Risk factors for multiple intracranial aneurysms.

BACKGROUND AND PURPOSE: The presence of multiple intracranial aneurysms may be a sign of significant risk factors for aneurysm formation that differ from those factors that increase risk for aneurysm rupture. Only 2 studies concern independent risk factors for multiple aneurysms, and the results are in part controversial. This study was designed to identify independent risk factors for multiple intracranial aneurysms in patients with subarachnoid hemorrhage. METHODS: Of 266 patients with aneurysmal subarachnoid hemorrhage (139 men and 127 women, aged 15 to 60 years), 80 (30%) had multiple intracranial aneurysms. The prevalence of several health-related habits, previous diseases, and medications of these patients were compared by multiple logistic regression between those with single and those with multiple aneurysms. RESULTS: On the basis of multivariate statistics, only regular cigarette smoking at any time was a significant risk factor for the presence of multiple aneurysms. The odds ratio (OR) of smoking for multiple aneurysms was 2.10 (95% CI, 1.06 to 4.13) after adjustment for age and sex. After additional adjustment for hypertension, the risk was 2.06 (95% CI, 1. 04 to 4.07). Of other variables, only age (OR, 1.02 per year; 95% CI, 1.00 to 1.05; P=0.09) and female sex (OR, 1.60; 95% CI, 0.90 to 2. 85; P=0.11) showed a tendency to increase the risk for multiple aneurysms after adjustment for smoking. On the other hand, patients with hypertension had significantly (P=0.029) more aneurysms (1. 61+/-1.04) than did those without (1.37+/-0.68), although they did not more frequently have multiple aneurysms. CONCLUSIONS: Cigarette smoking and possibly also age and female sex seem to be risk factors for multiple intracranial aneurysms in patients of working age who have suffered a subarachnoid hemorrhage. Patients with hypertension seem to have more aneurysms than those without.

Natural history of unruptured intracranial aneurysms: probability and risk factors for aneurysm rupture.

OBJECT: The authors conducted a study to investigate the long-term natural history of unruptured intracranial aneurysms and the predictive risk factors determining subsequent rupture in a patient population in which surgical selection of cases was not performed. METHODS: We followed 142 patients with 181 unruptured aneurysms from the 1950s until death or the occurrence of subarachnoid hemorrhage, or until the years 1997 to 1998. The annual and cumulative incidence of aneurysm rupture as well as several potential risk factors predictive of rupture were studied using life-table analyses and the Cox's proportional hazards regression models including time-dependent covariates. The median follow-up time was 19.7 years (range 0.8-38.9 years). During 2575 person years of follow up, there were 33 first-time episodes of hemorrhage from a previously unruptured aneurysm, giving an average annual incidence of 1.3%. In seventeen of these cases, hemorrhages led to the patients' deaths. The cumulative rate of bleeding was 10.5% at 10 years, 23.0% at 20 years, and 30.3% at 30 years after diagnosis. The diameter of the unruptured aneurysm(relative risk [RR] 1.11 per mm in diameter, 95% confidence interval [CI] 1.00-1.23, p = 0.05) and patient age at diagnosis inversely (RR 0.97 per year, 95% CI 0.93-1.00, p = 0.05) were significant independent predictors for a subsequent aneurysm rupture after adjustment for sex, hypertension, and aneurysm group. Active smoking status at the time of diagnosis was a significant risk factor for aneurysm rupture (RR 1.46, 95% CI 1.04-2.06, p = 0.033) after adjustment for the size of the aneurysm, age, sex, presence of hypertension, and aneurysm group. Active smoking status asa time-dependent covariate was an even more significant risk factor for aneurysm rupture (adjusted RR 3.04, 95% CI 1.21-7.66, p = 0.020). CONCLUSIONS: Cigarette smoking, size of the unruptured intracranial aneurysm, and age, inversely, are important factors determining risk for subsequent aneurysm rupture. The authors conclude that such unruptured aneurysms should be surgically treated irrespective of their size and of patients' smoking status, especially in young and middle-aged adults, if this is technically possible and if the patient's concurrent diseases are not contraindications. Cessation of smoking may also be a good alternative to surgery in older patients with small-sized aneurysms.

Recent heavy drinking of alcohol and embolic stroke.

BACKGROUND AND PURPOSE: Epidemiological evidence suggests that heavy alcohol consumption increases the risk for ischemic stroke, whereas light-to-moderate alcohol intake decreases the risk, but the role of different drinking patterns has remained unclear. We investigated recent light, moderate, and heavy alcohol drinking and former heavy drinking as risk factors for acute ischemic brain infarction by etiological subtype of stroke. METHODS: We compared 212 consecutive patients aged between 16 and 60 years, who were completely evaluated for the etiology of their ischemic stroke, with 274 control subjects admitted to the emergency unit of the same hospital. ORs, as estimates of multivariate relative risks (RRs), and 95% CIs after adjustment for possible confounding variables were calculated by logistic regression. The ORs were adjusted for age, sex, body mass index, hypertension, diabetes, hyperlipemia, current smoking, and history of migraine. RESULTS: Recent heavy drinking but not former heavy drinking was an independent risk factor for stroke (RR 1.82, 95% CI 1.08 to 3.05). Consumption of 151 to 300 g and >300 g alcohol within the week preceding the onset of stroke significantly increased the risk for cardioembolic and cryptogenic stroke. Consumption of >40 g alcohol within the preceding 24 hours increased the risk for cardiogenic embolism to the brain among those who had a high-risk source (RR 4.75, 95% CI 1.23 to 18.4), the risk for tandem embolism among those who had prominent large-artery atherosclerosis (RR 7.68, 95% CI 1.82 to 32.3), and the risk for cryptogenic stroke (RR 3.84, 95% CI 1.69 to 8.71). Light drinking did not increase the risk for stroke. CONCLUSIONS: We conclude that acute drinking of intoxicating amounts of alcohol may trigger the onset of embolic stroke among subjects who have a source of thrombus in the heart or the large arteries.

Alcohol intake and the risk of stroke.

Alcohol consumption has been reported to have both beneficial and harmful effects on the incidence of stroke. Different drinking habits may explain the diversity of the observations, but this is still unclear. We reviewed recent clinical and epidemiological studies to find out whether alcohol intake could increase or decrease the risk for stroke. By a systematic survey of literature published from 1989 to 1997, we identified 14 case-control studies addressing alcohol as a risk factor for haemorrhagic and ischaemic stroke morbidity and fulfilling the following criteria: the type of stroke was determined by a head computerised tomography scan on admission or at autopsy; and alcohol consumption was verified using structured questionnaires or by personal interviews. In some studies, adjustment for hypertension abolished the independent role of alcohol as a risk factor. On the other hand, the studies covering even recent alcohol intake showed in many cases that heavy drinking is an independent risk factor for most stroke subtypes, and that the risk may decrease relatively rapidly after the cessation of alcohol abuse. In some studies, regular light to moderate drinking seemed to be associated with a decreased risk for ischaemic stroke of atherothrombotic origin. In conclusion, recent heavy alcohol intake seems to be an independent risk factor for all major subtypes of stroke. The ultimate mechanisms leading to the increased risk are unclear. The significance of alcohol as a risk factor has been demonstrated in young subjects because they are more often heavy drinkers than the elderly. Several factors to explain the beneficial effect of light to moderate drinking have been proposed.