Executive function subdomains are associated with post-stroke functional outcome and permanent institutionalization.

BACKGROUND AND PURPOSE: Impairment of executive functions (EFs) is a common cognitive symptom post-stroke and affects independence in daily activities. Previous studies have often relied on brief cognitive tests not fully considering the wide spectrum of EF subdomains. A detailed assessment of EFs was used to examine which of the subdomains and tests have the strongest predictive value on post-stroke functional outcome and institutionalization in long-term follow-up. METHODS: A subsample of 62 patients from the Helsinki Stroke Aging Memory Study was evaluated with a battery of seven neuropsychological EF tests 3 months post-stroke and compared to 39 healthy control subjects. Functional impairment was evaluated with the modified Rankin Scale (mRS) and Instrumental Activities of Daily Living (IADL) scale at 3 months, and with the mRS at 15 months post-stroke. Institutionalization was reviewed from the national registers of permanent hospital admissions in up to 21-year follow-up. RESULTS: The stroke group performed more poorly than the control group in multiple EF tests. Tests of inhibition, set shifting, initiation, strategy formation and processing speed were associated with the mRS and IADL scale in stroke patients. EF subdomain scores of inhibition, set shifting and processing speed were associated with functional outcome. In addition, inhibition was associated with the risk for earlier institutionalization. CONCLUSIONS: Executive function was strongly associated with post-stroke functional impairment. In follow-up, poor inhibition was related to earlier permanent institutionalization. The results suggest the prognostic value of EF subdomains after stroke.

Embolic strokes of undetermined source in young adults: baseline characteristics and long-term outcome.

BACKGROUND AND PURPOSE: Embolic strokes of undetermined source (ESUS) are a recent entity, not yet thoroughly investigated in young stroke patients. The clinical characteristics and long-term risks of vascular events and all-cause mortality between young-onset ESUS and other aetiological subgroups were compared. METHODS: Patients with ESUS were identified amongst the 1008 patients aged 15-49 years with first-ever ischaemic stroke in Helsinki Young Stroke Registry, and primary end-points were defined as recurrent stroke, composite vascular events and all-cause mortality. Cumulative 15-year risks for each end-point were analysed with life tables and adjusted risks were based on Cox proportional hazard analyses. RESULTS: Of the 971 eligible patients, 203 (20.9%) were classified as ESUS. They were younger (median age 40 years, interquartile range 32-46 vs. 45 years, 39-47), more often female (43.3% vs. 35.7%) and had fewer cardiovascular risk factors than other modified TOAST groups. With a median follow-up time of 10.1 years, ESUS patients had the second lowest cumulative risk of recurrent stroke and composite vascular events and lowest mortality compared to other TOAST groups. Large-artery atherosclerosis and small vessel disease carried significantly higher risk for recurrent stroke than did ESUS, whilst no difference appeared between cardioembolism from high-risk sources and ESUS. CONCLUSIONS: In our cohort, ESUS patients were younger and had milder cardiovascular risk factor burden and generally better long-term outcome compared to other causes of young-onset stroke. The comparable risk of recurrent stroke between ESUS and high-risk sources of cardioembolism might suggest similarities in their pathophysiology.

Post-stroke cognitive impairment is common even after successful clinical recovery.

BACKGROUND AND PURPOSE: Cognitive impairment is common after stroke, but the prevalence and long-term significance of the diverse neuropsychological deficits on functional outcome are still not well known. The frequency and prognostic value of domain-specific cognitive impairments were investigated in a large cohort of ischaemic stroke patients. METHODS: Consecutive patients (n = 409), aged 55-85 years, from the acute stroke unit of the Helsinki University Hospital, Finland, were evaluated with extensive clinical and neuropsychological assessments 3 months post-stroke. Impairments within nine cognitive domains were determined according to age-appropriate normative data from a random healthy population. Functional disability was evaluated with the modified Rankin scale (mRS) 3 and 15 months post-stroke. RESULTS: In all, 83% patients showed impairment in at least one cognitive domain, whereas 50% patients were impaired in multiple (≥3) domains. In cases with excellent clinical recovery at 3 months (mRS = 0-1, no disability), the occurrence of any cognitive impairment was 71%. Memory, visuoconstructional and executive functions were most commonly impaired. A substantially smaller proportion of patients scored below the conventional or more stringent cut-offs in the Mini-Mental State Examination (MMSE). Domain-specific cognitive impairments were associated with functional dependence at 15 months regardless of stroke severity and other confounders. CONCLUSIONS: Cognitive impairment as evaluated with a comprehensive neuropsychological assessment is prevalent in stroke survivors even with successful clinical recovery. Typically multiple domains and complex cognitive abilities are affected. MMSE is not sensitive in detecting these symptoms. Post-stroke cognitive impairment is strongly related to poor functional outcome.

Lost potential of kidney and liver donors amongst deceased intracerebral hemorrhage patients.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) has high acute mortality. The number of potential kidney and liver donors amongst deceased ICH patients was estimated to improve our institutional guidelines on acute care of neurocritical patients to increase organ donation. METHODS: A chart review was carried out by a multi-professional team for consecutive ICH patients admitted to the emergency department at Helsinki University Central Hospital and dying within 14 days between 2005 and 2010. RESULTS: In all, 955 patients had follow-up data, of whom 254 (27%) died within 14 days and eight ended up as organ donors. An additional 51 potentially suitable donors not different from actual donors were identified: nine suitable for kidney donation, 11 for liver and 31 for both. In 49/51 (96%) cases prognosis seemed non-existent and do-not-resuscitate orders were issued early, which led to refrainment from intensive care in 76.5%. These potential donors differed from those ICH patients surviving a whole year (n = 529) by male preponderance, more severe symptoms (median National Institutes of Health Stroke Scale 25 vs. 6 and Glasgow Coma Scale 7 vs. 15), larger hematoma volumes of 24.8 cm(3) (vs. 6.7), and frequent finding of midline shift and intraventricular rupture of the hemorrhage in admission brain CT. Based on the results, our guidelines were revised towards more active treatment including mechanical ventilation for neurocritical patients at the emergency department for at least 48 h, resulting in an increase in organ donations in 2012. CONCLUSIONS: A considerable number of ICH patients are potential organ donors if the evaluation takes place on arrival and organ donation is considered as part of usual end-of-life care.

Higher baseline international normalized ratio value correlates with higher mortality in intracerebral hemorrhage during warfarin use.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulation (OAC). Our aim was to investigate the impact of the international normalized ratio (INR) level on mortality in OAC-associated ICH compared with non-OAC-associated ICH. METHODS: A retrospective chart review of consecutive ICH patients treated at the Helsinki University Central Hospital from January 2005 to March 2010 (n = 1013) was performed. An ICH was considered to be OAC-associated if the patient was on warfarin at ICH onset. The association of INR with 3-month mortality was adjusted in a multivariable logistic regression model for factors influencing the crude odds ratios (ORs) in bivariable logistic regression by more than 5%. RESULTS: One in eight ICHs was OAC-associated (n = 132). Of these, 50% had therapeutic INR (2.0-3.0), 7% had INR <2.0 and 43% had high INR (>3.0) on admission. Patients on OAC were older (median 76 vs. 66 years; P < 0.001) with more severe symptoms (median National Institutes of Health Stroke Scale 14 vs. 10; P < 0.001) and larger hematomas (median 11.4 vs. 9.7 ml; P < 0.001) on admission than patients not on OAC. After adjustment for confounders, 3-month mortality in the whole cohort was associated with higher baseline INR (OR 1.06; CI 1.03-1.09 per 0.1 increment). Mortality was higher with both therapeutic (51% at 3 months; OR 3.59; CI 1.50-8.60) and high (61%; OR 5.26; CI 1.94-14.27) INR values compared with non-OAC-associated ICH (29%). CONCLUSIONS: Patients with OAC-associated ICH had more severe strokes and higher mortality compared with patients with ICH not related to OAC. Higher baseline INR was associated with increased 3-month mortality.

Multiple brain infarcts in young adults: clues for etiologic diagnosis and prognostic impact.

BACKGROUND AND PURPOSE: There are little data on the etiology of multiple brain infarcts (MBI) and their impact on clinical outcome in young patients. METHODS: We studied 548 MRI-imaged patients (15-49 years) with a first-ever ischaemic stroke. Ischaemic lesions were categorized into three groups: single lesions, MBI in one or >1 circulation territories. Outcomes were unfavorable 3-month modified Rankin Scale (mRS) score of ≥ 2 and, during long-term follow-up (mean 8.20 ± 4.01 years), recurrent ischaemic stroke or death from any cause. RESULTS: Multiple brain infarcts occurred in 185 patients (33.8%; mean age 39.2 ± 8.2), of which 144 patients (26.3%) had lesions located in a single territory and 41 patients (7.5%) in multiple territories. Patients with MBI in a single territory were more likely than patients with single lesions to have a high-risk source of cardioembolism (CE) (9.0% vs. 3.0%; P = 0.001), large-artery atherosclerosis (8.3% vs. 4.9%; P = 0.012), vertebral (22% vs. 10%; P < 0.001) or carotid artery dissections (8.3% vs. 6.3%; P = 0.036), and MBI in multiple territories a high-risk source of CE (34% vs. 3.0%, P < 0.001). Adjusted for age, gender, baseline stroke severity, size of the largest lesion, and stroke subtype, MBI remained independently associated with an unfavorable 3-month outcome (odds ratio 2.84, 95% confidence interval 1.22-6.61). In multivariate Cox proportional hazards analysis, MBI had independent influence on the risk for death (hazard ratio 3.75, 1.58-8.86), but not on recurrent ischaemic stroke. CONCLUSIONS: Compared with the elderly, young stroke patients have a distinct stroke etiology underlying MBI, being an independent indicator of poor short-term outcome and long-term risk of death.

Young adult ischaemic stroke related acute symptomatic and late seizures: risk factors.

BACKGROUND AND PURPOSE: After first-ever ischaemic stroke, to assess the risk and baseline factors associated with acute symptomatic seizure (ASS) (occurring within 7 days) and late post-stroke seizure (LPS) (>7 days). METHODS: All consecutive patients aged 15-49 with first-ever ischaemic stroke between 1994 and 2007 treated at the Helsinki University Central Hospital were included, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (>6.1 mm) and hyponatremia (<137 mm), use of psychiatric medication, stroke severity (NIH Stroke Scale) and anatomical (Bamford criteria) and etiological (Trial of Org in Acute Stroke Treatment) stroke subtype. RESULTS: ASSs emerged in 35 (3.5%) patients. LPSs (n = 102) occurred at a cumulative rate of 6.1% at 1 year, 9.5% at 5 years and 11.5% at 10 years. In multivariate analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.91-46.14), moderate stroke severity (3.95, 1.86-8.41), cortical involvement (3.69, 1.66-8.18) and hyponatremia (3.26, 1.41-7.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94, 7.62-33.33), partial anterior circulation infarct (3.48, 1.52-7.93), history of ASS (3.94, 2.07-7.48), antidepressant use at the time of LPS (3.88, 2.46-6.11), hemorrhagic infarct (1.94, 1.19-3.15), male gender (1.79, 1.10-2.92) and hyperglycemia (1.62, 1.05-2.51). CONCLUSIONS: In young ischaemic stroke patients, the magnitude of seizure risk and the major risk factors were similar to older ischaemic stroke patients but risk factors for ASSs and LPSs differed.

Functional outcome in young adult ischemic stroke: impact of lipoproteins.

AIM: To determine the functional outcome in a cohort of young adults with ischemic stroke patients, focusing on components of lipid profile. METHODS: In our registry including consecutive patients with first-ever ischemic stroke aged 15-49 from 1994 to 2007, we analyzed predictors of 3-month functional outcome (modified Rankin Scale, mRS). Infarct size fell into small, medium, large posterior, or large anterior. Stroke severity was assessed with NIH Stroke Scale (NIHSS). Serum lipids were measured within 72 h after admission. Binary, multinomial ordinal, and Poisson regressions allowed revealing factors associated with size of infarct, stroke severity, and unfavorable outcome or death (mRS, 2-6) or mRS as an ordinal measure. RESULTS: In the 968 patients included (mean age, 41.3 ± 7.6; 62.6% men; 49.5% with mRS 0-1), factors associated with unfavorable outcome after multivariable analysis were increasing age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.05), higher NIHSS score (1.23 per point, 1.17-1.29), large anterior (4.37, 2.26-8.42) or posterior (1.73, 1.05-2.85) infarcts, bilateral lesions (2.28, 1.30-3.98), internal carotid artery dissection (ICAD) (3.65, 1.41-9.47), and inversely high-density lipoprotein (HDL) levels (0.58 per unit increase, 0.38-0.86). Increasing HDL associated with smaller infarct size (0.71, 0.51-0.98). Both higher total and HDL cholesterol associated with lower NIHSS score (0.96, 0.93-0.98 for total cholesterol and 0.82, 0.75-0.88 for HDL) and lower 3-month mRS (0.87, 0.78-0.97 for total cholesterol and 0.65, 0.47-0.90 for HDL). CONCLUSION: In addition to known prognosticators, ICAD and lower HDL levels were independently associated with adverse clinical outcomes in our young adult stroke cohort.

Hemiplegia and thrombolysis.

BACKGROUND AND PURPOSE: Hemiplegia at stroke onset may be considered a contraindication for thrombolytic therapy. We describe the outcome of patients with ischaemic stroke presenting with hemiplegia and treated with intravenous alteplase (tPA). METHODS: All patients treated with tPA for acute ischaemic stroke between 1995 and 2010 were prospectively recorded in the Helsinki Stroke Thrombolysis Registry. Patients with basilar artery occlusion (BAO) were excluded. Hemiplegia was defined as no visible voluntary movement on ipsilateral arm and leg. RESULTS: Of all treated patients (n = 1579), we excluded those with BAO (n = 152). Of remaining 1427 patients, 81 (6%) had hemiplegia at baseline. By 24 h, three had died and 20 retained their total hemiplegia. At day 7, a further nine had died, and 10 had persistent hemiplegia. A good 3-month outcome, modified Rankin Scale (mRS, 0-2), was observed in 23%, independence in ambulatory function (mRS 3) in further 16%, while 9% were bedridden and 20% dead. A wide clinical spectrum of neurological deficits coexisted with hemiplegia. With advanced age, more neurological functions lost, and with early radiological signs, the prognosis of patients with hemiplegia deteriorated. With combined fixed eye deviation (n = 23), half were either bedridden (n = 3) or dead (n = 9) by 3 months, and fatal intracerebral haemorrhage were common (n = 5). CONCLUSIONS: Hemiplegia at presentation should not prevent thrombolytic therapy by itself, as limb movements are likely to return, and two of five thrombolysis-treated patients will walk independently by 3 months. With combined fixed eye deviation, the outcome is poorer and haemorrhagic complications are common.

Extensive white matter changes predict stroke recurrence up to 5 years after a first-ever ischemic stroke.

BACKGROUND: White matter changes (WMCs), a surrogate for small-vessel disease (SVD), have been shown to be associated with a major negative influence on cognition, mood and functioning in daily life. We aimed to investigate whether severe WMCs are a risk factor for recurrent ischemic stroke in a long-term follow-up. METHODS: 320 consecutive patients admitted to hospital with a first-ever ischemic stroke were included in the study and followed up for 12 years using extensive national registers. Patients were aged between 55 and 85 years, with a mean age of 70.8 years. WMCs were rated using MRI and stratified into two grades: absent to moderate WMCs versus severe WMCs. Univariate analysis was performed using binary logistic regression analysis, Kaplan-Meier log rank analysis and life table function. To control for factors such as age, education and cardiovascular risk factors, a multivariate Cox regression proportional hazards analysis was made with forced entry. RESULTS: At least one recurrent stroke, nonfatal or fatal, was diagnosed in 76 (23.8%) patients at 5 years and in 127 (39.7%) patients at 12 years. In univariate analysis, only advancing age was associated with WMCs. The cumulative 5-year recurrence risk was 24.5% [95% confidence interval (95% CI) 23.8-25.2] for patients with absent to moderate WMCs and 39.1% (95% CI 38.1-40.1) for patients with severe WMCs. The cumulative 12-year recurrence risk was 48.1% (95% CI 45.5-50.7) for patients with absent to moderate WMCs and 60.9% (95% CI 56.7-65.1) for patients with severe WMCs. In Cox regression proportional hazards analysis, independent predictors of recurrent stroke at 5 years were severe WMCs [hazard ratio (HR) 1.80, 95% CI 1.11-2.95], atrial fibrillation (HR 1.81, 95% CI 1.09-3.02), hypertension (HR 1.69, 95% CI 1.05-2.71) and peripheral arterial disease (HR 1.89, 95% CI 1.06-3.38). At 12 years, only increasing age remained as an independent predictor (HR 1.04, 95% CI 1.02-1.07). In receiver operating characteristic analysis, the area under the curve for severe WMCs was 0.58 (95% CI 0.51-0.65) for the prediction of stroke recurrence within 5 years. CONCLUSIONS: In our well-defined cohort of poststroke patients, the presence of severe WMCs was an indicator of stroke recurrence up to 5 years after a first-ever ischemic stroke. WMCs can be considered as an SVD marker that summarizes the effects of several classical risk factors on the small-vessel brain network and therefore can be used as a score for risk stratification of stroke recurrence. Our findings further underline the poor long-term prognosis of cerebral SVD.

Intravenous thrombolysis in ischemic stroke patients with isolated homonymous hemianopia.

BACKGROUND: Patients with posterior ischemic stroke were usually excluded from thrombolytic treatment in clinical trials and clinical practice, and little is known about effectiveness of thrombolysis treatment in such patients who may end up with severe disability. AIMS OF THE STUDY: We aimed to describe the outcome of acute ischemic stroke patients presenting with isolated homonymous hemianopia and treated with intravenous thrombolysis. METHODS: A case report of three patients presenting with homonymous hemianopia owing to posterior circulation stroke treated with intravenous thrombolysis at the Helsinki University Central Hospital. Main outcome measures were modified Rankin Scale and neuropsychological examination at 3 months after thrombolysis. We further evaluated Goldmann visual field examination at 6 months. RESULTS: No acute findings appeared on admission non-contrast head-computed tomography scan. All patients had a perfusion deficit on admission-computed tomography perfusion imaging. All patients scored 0 on 3-month modified Rankin Scale, and their neuropsychological evaluation was normal. Goldmann examination revealed no visual field deficit in both female patients, and a modest visual field defect was detected in the male patient. CONCLUSIONS: Our experience encourages application of intravenous thrombolytic treatment (especially when supported with multimodality neuroimaging) in patients with homonymous hemianopia, for which rehabilitation options are limited.

Non-cholesterol sterols in serum and endarterectomized carotid arteries after a short-term plant stanol and sterol ester challenge.

BACKGROUND AND AIMS: It is not known whether dietary intake of plant stanols or sterols changes the composition of arterial sterols. Therefore, we compared serum and carotid artery cholesterol and non-cholesterol sterols after plant stanol (staest) or sterol (steest) ester feeding in endarterectomized patients. METHODS AND RESULTS: Elderly statin-treated asymptomatic patients undergoing carotid endarterectomy were randomized double-blind to consume staest (n=11) or steest (n=11) spread (2 g of stanol or sterol/day) for four weeks preoperatively. Non-cholesterol sterols from serum and carotid artery tissue were analysed with gas-liquid chromatography. Staest spread lowered serum total (17.2%), VLDL, and LDL cholesterol and serum triglycerides, while steest spread lowered serum total (13.8%) and LDL cholesterol levels from baseline (p<0.05 for all). Serum cholestanol and avenasterol were decreased in both groups, but campesterol and sitosterol were decreased by staest and increased by steest from baseline (p<0.05 from baseline and between the groups). Serum sitostanol to cholesterol ratio was increased by staest, but in arterial tissue this ratio was similar in both groups. On staest, lathosterol, campesterol, and sitosterol, and on steest sitosterol and avenasterol correlated significantly between serum and arterial tissue. Cholesterol metabolism, eg. lathosterol/campesterol, suggested that plant sterols were reduced in serum and in arterial tissue during staest. CONCLUSION: The novel observations were that plant stanol ester consumption, in contrast to plant sterols, tended to reduce carotid artery plant sterols in statin-treated patients. Furthermore, despite increased serum sitostanol contents during plant stanol ester consumption, their arterial levels were unchanged suggesting that sitostanol is not taken up into the arterial wall.

Age related white matter changes predict stroke death in long term follow-up.

OBJECTIVE: Recurrent strokes and functional decline are predicted by age related white matter changes (ARWMC). Whether they are associated with long term survival among hospital patients referred for acute stroke is not known. METHODS: A total of 396 consecutive acute stroke patients subjected to MRI were included in the study and followed-up for up to 12 years. RESULTS: 28% had mild, 18% had moderate and 54% had severe ARWMCs. In Kaplan-Meier analysis, poor survival was predicted by severe ARWMCs (p<0.0001), cardiac failure (CF, p<0.0001), atrial fibrillation (AF, p<0.0001), other arrhythmias (p = 0.003), peripheral arterial disease (PAD, p = 0.004) and poor modified Rankin score (mRS) (p<0.0001). ARWMC was related to death by all brain related causes, especially ischaemic stroke (p<0.0001). In stepwise Cox regression analysis adjusted with significant risk factors, severe ARWMCs (hazard ratio (HR) 1.34, 95% CI 1.03 to 1.73; p = 0.029), age (HR 1.07, 95% CI 1.05 to 1.09; p<0.0001), CF (HR 1.59, 95% CI 1.17 to 2.15; p = 0.003), AF (HR 1.68, 95% CI 1.24 to 2.27; p = 0.001), PAD (HR 1.59, 95% CI 1.11 to 2.26; p = 0.011), diabetes (HR 1.44, 95% CI 1.08 to 1.92; p = 0.013), smoking (HR 1.60, 95% CI 1.23 to 2.08; p<0.0001) and mRS (HR 1.65, 95% CI 1.26 to 2.14; p<0.0001) were independently associated with death from all causes. Severe ARWMCs (HR 1.80, 95% CI 1.10 to 2.96; p = 0.019), age (HR 1.05, 95% CI 1.01 to 1.09; p = 0.009), AF (HR 1.82, 95% CI 1.08 to 3.07; p = 0.026), PAD (HR 2.17, 95% CI 1.19 to 3.95; p = 0.012) and mRS (HR 2.75, 95% CI 1.67 to 4.54; p<0.0001) were specifically associated with death from brain related causes. CONCLUSIONS: In patients with acute stroke, ARWMC seems to be a significant predictor of poor long term survival and death by ischaemic stroke.

Cognitive impairment predicts poststroke death in long-term follow-up.

BACKGROUND: Poststroke global cognitive decline and dementia have been related to poor long-term survival. Whether deficits in specific cognitive domains are associated with long-term survival in patients with ischaemic stroke is not known in detail. METHODS: Patients with acute stroke subjected to comprehensive neuropsychological evaluation were included in the study (n = 409) and followed up for up to 12 years. RESULTS: In Kaplan-Meier analysis, impairments in following cognitive domains predicted poor poststroke survival (estimated years): executive functions (48.2%) (5.8 vs 10.1 years, p<0.0001), memory (59.9%) (6.8 vs 9.3 years, p = 0.009), language (28.9%) (5.3 vs 8.6 years, p = 0.004) and visuospatial/constructional abilities (55.2%) (5.6 vs 10.1 years, p<0.0001). Low Mini Mental Status Examination (MMSE)

Poststroke dementia predicts poor survival in long-term follow-up: influence of prestroke cognitive decline and previous stroke.

BACKGROUND: The aim of this study was to investigate the influence of poststroke dementia on long-term survival after acute stroke and also to assess the possible influence of prestroke cognitive decline and previous stroke on this relationship. METHODS: A total of 451 consecutive patients with acute ischaemic stroke admitted to hospital were included in the study and followed up for 12 years. Dementia was diagnosed 3 months after stroke in 115 patients (25.5%). RESULTS: In Kaplan-Meier analysis, poststroke dementia predicted poor long-term survival (5.1 years vs 8.8 years in patients who did not have poststroke dementia; p<0.001). Prestroke cognitive decline had a negative influence on survival in patients with poststroke dementia (3.8 years vs 5.8 years; p<0.001); however, previous stroke did not affect survival in these patients (p = 0.676). In stepwise Cox regression proportional hazards analysis adjusted for significant covariates, poststroke dementia (hazard ratio (HR) 1.53; p = 0.003), advanced age (HR 1.07; p<0.001), severity of stroke (HR 1.91; p<0.001), smoking (HR 1.35; p = 0.035), cardiac failure (HR 1.61; p = 0.003) and atrial fibrillation (HR 1.89; p = 0.035) were all independent predictors of poor long-term survival. Poststroke dementia (HR 2.33; p<0.001), advanced age (HR 1.07; p<0.001) and poor Rankin score (HR 2.15; p = 0.001) were associated with death from brain-related causes, including infarction, haemorrhage and dementia. CONCLUSIONS: Long-term follow-up of our large well-defined poststroke cohort indicated that in patients with acute stroke, dementia is a significant predictor of poor long-term survival and death from brain-associated causes. Prestroke cognitive decline seems to have an additional negative influence on survival, but previous stroke does not seem to affect survival.

Adult cervicocerebral artery dissection: a single-center study of 301 Finnish patients.

BACKGROUND AND PURPOSE: There are only few small studies assessing potential risk factors, comorbidity, and prognostic factors in adult spontaneous cervicocerebral artery dissection (CAD). METHODS: We conducted a retrospective, hospital-based analysis on the prognostic factors and association of CAD with vascular risk factors in 301 consecutive Finnish patients, diagnosed from 1994 to 2007. RESULTS: Two thirds of the patients were men (68%). Women were younger than men. Migraine (36% of all patients), especially with visual aura (63% of all migraineurs), and smoking were more common in patients with CAD compared with the general Finnish population. At 3 months, 247 (83%) patients reached a favorable outcome. Occlusion of the dissected artery, internal carotid artery dissection (ICAD), and recent infection in infarction patients were associated with a poorer outcome. ICAD patients had less often brain infarction, but the strokes they had were more severe. Seven (2.3%) patients died during the follow-up (mean 4.0 years, 1186 patient years). Six (2%) patients had verified CAD recurrence. CONCLUSIONS: This study provides evidence for the association of CAD with male sex, and possible association with smoking and migraine. Occlusion of the dissected artery, ICAD, and infection appear to be associated with poorer outcome.

Long-term survival after ischemic stroke in postmenopausal women is affected by an interaction between smoking and genetic variation in nitric oxide synthases.

BACKGROUND: We aimed to study whether variations in vasoregulatory endothelial nitric oxide synthase (eNOS 4a/b) and tissue-injury-associated inducible nitric oxide synthase (iNOS R5/4) genes and smoking might explain gender differences in long-term survival after stroke. METHODS: A total of 486 consecutive acute stroke patients, subjected to MRI, were followed up for a mean of 7.6 years. The eNOS 4a/b (n = 300) and iNOS R5/4 (n = 310) genotypes were determined by PCR. Of these patients, 213/300 (71.0%; eNOS 4a/b) and 223/310 (71.9%; iNOS R5/4) had died. RESULTS: Despite the fact that women were older than men (72.3 vs. 69.5 years, p = 0.001) at recruitment, poor long-term survival was not sex-related, but instead predicted by age (p < 0.0001), cardiac failure (p = 0.004), smoking (p = 0.017), diabetes (p = 0.049), and variation in the eNOS gene locus (p = 0.033). Smoking and variations in both eNOS [hazard ratio (HR) = 1.53, p = 0.011] and iNOS loci (HR = 1.52, p = 0.073) were found to impact upon poor survival. We found a strong interaction between smoking, female sex, and the iNOS R5/4 genotype with the risk of death (HR = 3.23, CI = 1.51-6.90, p = 0.002). Compared with nonsmoking noncarriers, postmenopausal women who had been smokers and carried either the rare iNOS R5 allele (17.1%; HR = 4.23, CI = 1.84-9.75, p = 0.001) or the common eNOS 4b allele (71%; HR = 3.14, CI = 1.49-6.62, p = 0.003) were at a higher risk of death during the follow-up. These interactions were independent of each other, and were not found among men. CONCLUSIONS: The interaction between smoking and genetic variants of eNOS and iNOS predicts survival after stroke, especially among postmenopausal women.

Serial measurements of plasma homocysteine levels in early and late phases of ischemic stroke.

High plasma levels of homocysteine (Hcy) may predispose to ischemic stroke (IS), but results of previous studies have been conflicting. We decided to determine in IS patients whether their Hcy levels are elevated, whether levels vary at different time points following stroke, whether levels are associated with stroke severity, outcome, recurrence, etiology, infarct volume, or risk factors, and whether levels are correlated with hemostatic factors or C-reactive protein values. We measured plasma Hcy levels in 102 consecutive IS patients on admission and at 1 week, 1 month, and 3 months after stroke and once in 102 control subjects. Hemostatic factors were measured in 55 patients. Compared with controls, plasma Hcy levels in patients were significantly lower on admission but not at later time points, with levels increasing by week and remaining at this level for 3 months. Hcy levels showed a positive correlation with age and a negative correlation with Mini-Mental State Examination (MMSE) scores. Plasma Hcy levels inversely correlated with plasminogen activator inhibitor type-1. Decreased Hcy levels on admission may reflect the strength of the acute-phase response rather than a pathogenetic event. The negative correlation between Hcy levels and MMSE scores is more probably age-related than stroke-related.

Magnetic resonance imaging correlates of depression after ischemic stroke.

BACKGROUND: Depression affects up to 40% of patients with ischemic stroke. The relationship between site and size of brain infarcts and poststroke depression is still not well characterized. Further possible contribution and interaction of white matter lesions and brain atrophy has not been studied previously. We conducted a magnetic resonance image-based study of the radiologic correlates of depression in a large, well-defined series of patients with ischemic stroke. METHODS: Modified DSM-III-R and DSM-IV criteria were used to diagnose depressive disorders during a comprehensive psychiatric evaluation in 275 of 486 consecutive patients aged 55 to 85 years 3 to 4 months after ischemic stroke. A standardized magnetic resonance imaging protocol detailed side, site, type, and extent of brain infarcts and extent of white matter lesions and brain atrophy. RESULTS: Depressive disorders were diagnosed in 109 patients (40%). Patients with depression had a higher number and larger volume of infarcts affecting the prefrontosubcortical circuits, especially the caudate, pallidum, and genu of internal capsule, with left-sided predominance. Extent of white matter lesions and atrophy did not differ in patients with and without depression. Independent correlates of poststroke depression in a logistic regression model were mean frequency of infarcts in the genu of internal capsule on the left side (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.0-10.1), mean frequency of infarcts in the pallidum of any side (OR, 1.6; 95% CI, 1.1-2.3), and mean volume of infarcts in the right occipital lobe (OR, 0.98; 95% CI, 0.96-0.99). CONCLUSION: Lesions affecting the prefrontosubcortical circuits, especially on the left side, are correlates of depression after ischemic stroke.