Fatigue 7 years post-stroke: Predictors and correlated features.

BACKGROUND: Post-stroke fatigue (PSF) is common with great impact on quality of life. We explored predictive and cross-sectionally correlated features in the long term after ischemic stroke. METHODS: This study comprises 430 participants of the prospective Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), aged 18-69 years at index stroke. Information on acute stroke severity and cardiovascular risk factors was collected at index stroke. After 7 years, PSF was assessed by the Daily Fatigue Impact Scale (D-FIS). Cognitive, neurological, and functional outcomes, and symptoms of depression and anxiety, pain, insomnia, and physical activity were also assessed. Associations between baseline variables and PSF were analyzed by ordinal regression. Correlations between PSF and cross-sectionally assessed variables, and between PSF and baseline variables, were analyzed with Spearman's or point-biserial correlation for the whole sample and in sex-stratified analyses. RESULTS: At 7 years post-stroke, 80% of the participants reported some impact of fatigue. Female sex and stroke severity were independently associated with PSF, whereas no associations were detected with baseline cardiovascular risk factors. In cross-sectional analyses at 7 years, we found correlations between PSF and poor functional, neurological, and cognitive outcomes, as well as depressive symptoms, anxiety, insomnia, pain, and low physical activity (p < .001 throughout). The correlation with insomnia was stronger in women than in men (two-way ANOVA interaction test, p = .03). CONCLUSIONS: Our findings confirm that PSF is common in the long term after ischemic stroke and show a complex interplay with sex and several other outcomes. Future studies should address causal relationships and interventions towards fatigue and coexisting features.

Forty-four-year longitudinal study of stroke incidence and risk factors - the Prospective Population Study of Women in Gothenburg.

OBJECTIVE: To assess stroke incidence over 44 years and association with risk factors. To study total stroke incidence at 60-82 years of age and risk factors. DESIGN: Prospective population study. SETTING: Gothenburg, Sweden, with ∼450,000 inhabitants. SUBJECTS: A representative sample of a general population of women (1462 in total) in 5 age strata aged 38-60 years in 1968-1969 (the Population Study of Women in Gothenburg, PSWG) were followed up to the ages of 82-104 years in 2012. Further, analysis was also performed for the age interval 60-82 years. MAIN OUTCOME MEASURES: Incidence of total stroke (TS), ischaemic (IS), haemorrhagic (HS), non-specified (NS) and fatal (FS) strokes and association with baseline classic risk factors (such as hypertension, atrial fibrillation, low physical activity, diabetes, high waist-hip-ratio, hyperlipidaemia, smoking), low education, mental stress, pre-eclampsia and oral health as expressed by loss of teeth and bone score. Blood pressure in levels 1-3 according to modern guidelines. Associations with atrial fibrillation, diabetes and myocardial infarction shown in survival analyses. The five cohorts contributed to risk time data concerning associations with TS in the 60-82 age interval from the examination performed when they were 60. RESULTS: Three hundred and thirty-seven (23%) women had a first-ever stroke, 64 (19%) fatal. TS was associated with physical inactivity, high triglycerides and low education in multivariable analysis. The main sub-type IS was associated with systolic blood pressure, physical inactivity and low education. Pre-eclampsia showed association with IS only in the univariable analysis. FS was associated with systolic blood pressure and smoking. During 60-82 years of age, having <20 teeth (HR 1.74, CI 1.25-2.42), diabetes (HR 2.28 CI 1.09-4.76), WHR (HR 1.29 per 0.1 units CI 1.01-1.63), systolic blood pressure (HR 1.11 per 10 units CI 1.04-1.18) and smoking (HR 1.57, CI 1.14-2.16), were associated with TS in the combined five cohorts. CONCLUSIONS: Several classic risk factors showed independent associations with stroke. Vulnerability factors as low education and oral health, reflected by loss of teeth, also showed association with stroke. All these factors are possible to target in primary care preventive interventions.Key PointsStroke is a common disease and the risk of stroke is a key issue demanding preventive strategies in primary health care. The present prospective population study of women showsOut of 1460 women, almost a quarter got a stroke. The stroke incidence 60-82 years of age was rather stable between the first four age cohorts but somewhat lower in the latest cohort, born 1930.Hypertension, low physical activity, low education and high triglyceride levels but not cholesterol were associated with stroke in women.Low education and loss of teeth are vulnerability factors that should need particular attention.

Cognitive function is an important determinant of employment amongst young ischaemic stroke survivors with good physical recovery.

BACKGROUND AND PURPOSE: This cross-sectional cohort study aims at investigating young ischaemic stroke survivors with good physical recovery 7 years post-stroke in order to analyze the relation between late cognitive ability and employment. METHODS: Consecutive ischaemic stroke survivors participating in the Sahlgrenska Academy Study on Ischemic Stroke, <55 years of age at stroke onset, and with no or minimal persisting neurological deficits corresponding to a score ≤2 on the National Institutes of Health Stroke Scale at long-term follow-up 7 years post-stroke were included. At this follow-up, the participants were assessed with respect to general cognitive function, processing speed, executive functions, cardiovascular risk factors, self-reported employment, cognitive difficulties, fatigue, depressive symptoms, anxiety and physical function. RESULTS: Seven years post-stroke 112/142 (79%) had part-time or full-time work and 30/142 (21%) had full-time disability pension or sick leave. Compared to those with full-time disability pension or sick leave, participants with current employment demonstrated significantly better performance with respect to general cognitive function and processing speed, and significantly lower self-ratings for cognitive difficulties, physical limitations, fatigue and depressed mood. Multivariable logistic regression selected self-rated memory (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.61-4.21), processing speed (OR 3.50, 95% CI 1.67-7.33) and self-rated communication skills (OR 3.46, 95% CI 1.75-6.85) as most important correlates (area under the curve 0.83-0.87) of having current employment. CONCLUSION: This study indicates that cognitive dysfunction is an important contributor to long-term work disability amongst young stroke survivors with good physical recovery.

Plasma neurofilament light chain levels predict improvement in late phase after stroke.

BACKGROUND AND PURPOSE: Although functional recovery is most pronounced in the first 6 months after stroke, improvement is possible also in the late phase. The value of plasma neurofilament light chain (NfL), a biomarker of axonal injury and secondary neurodegeneration, was explored for the prediction of functional improvement in the late phase after stroke. METHODS: Baseline plasma NfL levels were measured in 115 participants of a trial on the efficacy of multimodal rehabilitation in the late phase after stroke. The association between NfL levels, impairment in balance, gait and cognitive domains, and improvement 3 and 9 months later was determined. RESULTS: Plasma NfL levels were associated with the degree of impairment in all three domains. Individuals with meaningful improvement in balance and gait capacity had higher plasma NfL levels compared with non-improvers (p = 0.001 and p = 0.018, respectively). Higher NfL levels were associated with improvement in balance (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.35-4.27, p = 0.004) and gait (OR 2.27, 95% CI 1.25-4.32, p = 0.009). Elevated plasma NfL levels showed a positive predictive value for cognitive improvement, and this effect was specific for the intervention targeting the cognitive domain. The association of NfL levels with cognitive improvement withstood correction for baseline impairment, age and total years of schooling (OR 7.54, 95% CI 1.52-45.66, p = 0.018). CONCLUSIONS: In addition to its established role as a biomarker in the acute phase, elevated circulating NfL levels may predict functional improvement in the late phase after stroke. Our results should prompt further studies into the use of plasma NfL as a biomarker in the late phase after stroke.

Proinflammatory protein signatures in cryptogenic and large artery atherosclerosis stroke.

OBJECTIVES: The cause of ischemic stroke remains unknown, cryptogenic, in 25% of young and middle-aged patients. We hypothesized that if atherosclerosis is prominent in cryptogenic stroke, it would have a similar proinflammatory protein signature as large artery atherosclerosis (LAA) stroke. MATERIALS & METHODS: Blood was collected in the acute phase and after 3 months from cryptogenic (n = 162) and LAA (n = 73) stroke patients aged 18-69 years and once from age-matched controls (n = 235). Cryptogenic stroke was divided into Framingham Risk Score (FRS) quartiles to compare low and high risk of atherosclerosis. Plasma concentrations of 25 proteins were analyzed using a Luminex multiplex assay. The discriminating properties were assessed with discriminant analysis and C-statistics. RESULTS: We identified proteins that separated cryptogenic and LAA stroke from controls (area under the curves, AUCs ≥ 0.85). For both subtypes, RANTES, IL-4, and IFN-γ contributed the most at both time points. These associations were independent of risk factors of atherosclerosis. We also identified proteins that separated cryptogenic strokes in the lowest quartile of FRS from those in the highest, and from LAA stroke (AUCs ≥ 0.76), and here eotaxin and MCP-1 contributed the most. CONCLUSIONS: The protein signature separating cases from controls was different from the signature separating cryptogenic stroke with low risk of atherosclerosis from those with high risk and from LAA stroke. This suggests that increased RANTES, IL-4, and IFN-γ in stroke may not be primarily related to atherosclerosis, whereas increased eotaxin and MCP-1 in cryptogenic stroke may be markers of occult atherosclerosis as the underlying cause.

The presence and prediction of lateralized inattention 7 years post-stroke.

OBJECTIVE: Lateralized inattention is a typical sign of neglect and related to poor functional outcome. Knowledge of the long-term course of this phenomenon is limited. The purpose of this study was to investigate presence and predictors for signs of lateralized inattention 7 years after stroke. METHODS: From a cohort of acute ischemic stroke patients, aged 18-69 years (n = 297), a consecutive series of 188 survivors without recurrent stroke at follow-up 7 years later were included. Within the first week after stroke onset, stroke severity was assessed according to the Scandinavian Stroke Scale. Target omissions, asymmetry of omissions, and perceptual speed according to Star- and Letter Cancellation Tests were also assessed. Presence of lateralized inattention at the 7-year follow-up was investigated with the Star- and Letter Cancellation Tests and with the neglect item in the National Institutes of Health Stroke Scale. RESULTS: At the follow-up, 22 (11.7%) participants had lateralized inattention and the multivariable regression showed that independent significant baseline predictors were total omissions in target cancellations (P < .001) and inferior baseline performance on visual processing speed (P = .008). CONCLUSION: About one of ten individuals exhibited signs of lateralized inattention 7 years after stroke. Baseline performance in perceptual processing speed and target omissions independently predicted presence of late signs of lateralized inattention. This is the first time processing speed is recognized as a significant predictor of lateralized inattention several years after the stroke incidence, indicating that the longitudinal course of processing speed following stroke is a critical subject for future research.

Lifetime risk of stroke in the general male population.

OBJECTIVES: Most previous studies of incidence rates of stroke are from register studies, while data from prospective cohort studies are limited. The aim of the present study was to describe hazard rates, prevalence and cumulative proportion free from stroke during a lifelong follow-up of a representative sample of middle-aged men sampled from the general population. METHODS: A population-based sample of 855 men, all born in 1913, was investigated at 50 years of age and followed up with repeated medical examinations at age 54, 60, 67, 75 and 80. Data from hospital records and the Cause of Death Register were collected, and all stroke events during 48 years of follow-up were registered. Medical records were scrutinized in order to confirm and validate the stroke diagnoses. RESULTS: One man was excluded because of stroke prior to baseline, while 176 of the remaining 854 men (20.7%) suffered a first-ever stroke during follow-up. The total 5-year stroke risk (hazard rate) increased with age, from 3.54 (95% CI: 0-7.55) per 1000 persons at risk at age 50 years, to 119.05 (95% CI: 45.39-192.70) at age 90 years. The stroke prevalence peaked at age 80 and older, with about 120 cases per 1000 years of observation. The survival rate (cumulative proportion free from stroke) at age 98 was 50.0%. CONCLUSION: One out of five men in this population sample suffered a stroke of any type during follow-up from 50 to 98 years of age and the cumulative incidence was close to 50%.

Homeostasis model assessment of insulin resistance and outcome of ischemic stroke in non-diabetic patients - a prospective observational study.

BACKGROUND: Insulin resistance (IR) in relation to diabetes is a risk factor for ischemic stroke (IS), whereas less is known about non-diabetic IR and outcome after IS. METHODS: In non-diabetic IS (n = 441) and controls (n = 560) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), IR was investigated in relation to IS severity and functional outcome. IR was evaluated acutely and after 3 months using the Homeostasis model assessment of IR (HOMA-IR). Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was evaluated using the modified Rankin Scale (mRS) after 3 months, 2 and 7 years. Associations were evaluated by logistic regression. RESULTS: Higher acute and 3-month HOMA-IR was observed in IS compared to the controls (both p < 0.001) and in severe compared to mild IS (both p < 0.05). High acute HOMA-IR was associated with poor outcome (mRS 3-6) after 3 months and 7 years [crude Odds ratios (ORs), 95% confidence intervals (CIs) 1.50, 1.07-2.11 and 1.59, 1.11-2.30, respectively], but not after 2 years. These associations lost significance after adjustment for all covariates including initial stroke severity. In the largest IS subtype (cryptogenic stroke), acute HOMA-IR was associated with poor outcome after 2 years also after adjustment for age and stroke severity (OR 2.86, 95% CI 1.01-8.12). CONCLUSIONS: In non-diabetic IS patients, HOMA-IR was elevated and related to stroke severity, but after adjustment for IS severity, the associations between HOMR-IR and poor outcome lost significance. This could suggest that elevated IR mostly is a part of the acute IS morbidity. However, in the subgroup of cryptogenic stroke, the associations with poor outcome withstood correction for stroke severity.

Determinants of Stroke in a General Male Population.

Background and Purpose- To further improve preventive strategies against stroke, there is a need for epidemiological long-term studies. The study aimed at a prospective investigation of stroke determinants in the general male population. Methods- During a period of 48 years, from 50 to 98 years of age, a population-based sample of 854 men was followed using repeated medical examinations, lifestyle questionnaires, data from hospital records and the National Cause of Death Register. Results- Determinants of ischemic stroke were atrial fibrillation (hazard ratio [HR], 6.61; 95% CI, 4.47-9.77); mother dead from cardiovascular disease (HR, 1.53; 1.09-2.17); high education (HR, 0.81; 0.69-0.96); and high physical activity level during leisure time (HR, 0.68; 0.50-0.93). For hemorrhagic stroke heart rate (HR, 1.04; 1.01-1.06) and mother dead from stroke (HR, 3.56; 1.43-8.87) constituted an increased risk. Statistically significant determinants for all stroke were atrial fibrillation (HR, 5.34; 3.68-7.75); high diastolic blood pressure (HR, 1.02; 1.01-1.03); high body weight (HR, 0.96; 0.94-0.99); high educational level (HR, 0.79; 0.68-0.92); wide waist circumference (HR, 1.04; 1.01-1.07); smoking (HR, 1.25; 1.06-1.48); mother dead from cerebrovascular disease (HR, 1.43; 1.05-1.94); and diabetes mellitus (HR, 1.65; 1.02-2.68). Of all men diagnosed with atrial fibrillation, 88% had a stroke during follow-up. Conclusions- Atrial fibrillation was by far the strongest determinant of stroke during 48 years of follow-up in a male population sample followed until the age of 98 years. The results warrant improved prophylaxis through intense treatment of modifiable determinants.

Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study.

BACKGROUND: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (ΔIGF-I, further transformed into ΔIGF-I-quintiles, ΔIGF-I-q) are associated with IS severity and outcome. METHODS: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N = 354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years. RESULTS: In general, the levels of s-IGF-I decreased (positive ΔIGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd ΔIGF-I-q showed the strongest association to mRS 0-2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18-11.9], and after 2 years, the 5th ΔIGF-I-q (OR 3.63, 95% CI 1.40-9.38) showed the strongest association to mRS 0-2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p = 0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p = 0.035), whereas the 2-year associations were further attenuated (p = 0.31). CONCLUSIONS: Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions.

Long-term progression of white matter hyperintensities in ischemic stroke.

OBJECTIVES: Studies on long-term progression of white matter hyperintensities (WMH) after ischemic stroke are scarce. Here, we sought to investigate this progression and its predictors in a cohort presenting with ischemic stroke before 70 years of age. MATERIALS AND METHODS: Participants in the Sahlgrenska Academy Study on Ischemic Stroke who underwent magnetic resonance imaging (MRI) of the brain at index stroke were examined by MRI again after 7 years (n = 188, mean age 53 years at index stroke, 35% females). WMH at index stroke and progression were assessed according to Fazekas' grades and the WMH change scale. Stroke subtype was classified according to TOAST. RESULTS: Marked WMH at index stroke were present in 20% of the participants and were significantly associated with age, hypertension, and subtype. Progression of WMH after 7 years was observed in 63% and 35% of the participants for subcortical and periventricular locations, respectively. Significant independent predictors of progression were age and marked WMH at baseline for both locations, whereas no significant associations were detected for vascular risk factors or subtype in multivariable analyses. In participants with no or only mild WMH at baseline, 20% showed marked WMH at follow-up. Age and hypertension, but not subtype, were independently associated with this acquisition of marked WMH. CONCLUSIONS: Age and marked WMH at index stroke, but not stroke subtype, predicted long-term WMH progression after ischemic stroke before 70 years of age, whereas age and hypertension predicted acquisition of marked WMH in those with no or only mild WMH at baseline.

Long-Term Improvements After Multimodal Rehabilitation in Late Phase After Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Treatments that improve function in late phase after stroke are urgently needed. We assessed whether multimodal interventions based on rhythm-and-music therapy or horse-riding therapy could lead to increased perceived recovery and functional improvement in a mixed population of individuals in late phase after stroke. METHODS: Participants were assigned to rhythm-and-music therapy, horse-riding therapy, or control using concealed randomization, stratified with respect to sex and stroke laterality. Therapy was given twice a week for 12 weeks. The primary outcome was change in participants' perception of stroke recovery as assessed by the Stroke Impact Scale with an intention-to-treat analysis. Secondary objective outcome measures were changes in balance, gait, grip strength, and cognition. Blinded assessments were performed at baseline, postintervention, and at 3- and 6-month follow-up. RESULTS: One hundred twenty-three participants were assigned to rhythm-and-music therapy (n=41), horse-riding therapy (n=41), or control (n=41). Post-intervention, the perception of stroke recovery (mean change from baseline on a scale ranging from 1 to 100) was higher among rhythm-and-music therapy (5.2 [95% confidence interval, 0.79-9.61]) and horse-riding therapy participants (9.8 [95% confidence interval, 6.00-13.66]), compared with controls (-0.5 [-3.20 to 2.28]); P=0.001 (1-way ANOVA). The improvements were sustained in both intervention groups 6 months later, and corresponding gains were observed for the secondary outcomes. CONCLUSIONS: Multimodal interventions can improve long-term perception of recovery, as well as balance, gait, grip strength, and working memory in a mixed population of individuals in late phase after stroke. CLINICAL TRIAL REGISTRATION: URL: http//www.ClinicalTrials.gov. Unique identifier: NCT01372059.

Stroke survivors' long-term QALY-weights in relation to their spouses' QALY-weights and informal support: a cross-sectional study.

BACKGROUND: Healthcare interventions that have positive effects on the stroke survivors' health-related quality of life (HRQoL) and quality-adjusted life-years (QALYs) might also have positive effects for their spouses in terms of improved HRQoL and/or reduced spousal informal support. However, knowledge about stroke survivors' HRQoL and QALY and the consequences for their spouses' HRQoL and QALY is limited. Therefore, the aim of this study was to describe the HRQoL and QALY-weights in dyads of stroke survivors in comparison with dyads of healthy controls, and to study the relationship between the stroke survivors' QALY-weights and consequences for spouses in terms of QALY-weight and annual cost of informal support, using a long-term perspective. METHODS: Data on stroke survivors, controls, and spouses were collected from the seven-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). HRQoL was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. The magnitude of the support was assessed with a study specific time-diary. An ordinary least squares (OLS) regression was used to estimate the association between stroke survivors' and spouses' QALY-weights. A two-part econometric model was used to estimate the association between stroke survivors' QALY-weights and the time spent and cost of spouses' informal support. RESULTS: Cohabitant dyads of 248 stroke survivors' aged <70 at stroke onset and 245 controls were included in the study. Stroke survivors had lower HRQoL in the SF-36 domains physical functioning, physical role, general health, vitality (P < 0.001), and social functioning (P = 0.005) in comparison with their cohabitant spouses. There was no significant difference in HRQoL for the dyads of controls. The results from the regression analyses showed that lower QALY-weights of the stroke survivors were associated with lower QALY-weights of their spouses and increased annual cost of spousal informal support. CONCLUSION: Our results show that the QALY-weights for stroke survivors had consequences for their spouses in terms of annual cost of spousal informal support and QALY-weights. Hence, economic evaluation of interventions that improve the HRQoL of the stroke survivors but ignore the consequences for their spouses may underestimate the value of the intervention.

Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors.

PURPOSE: The aim of this study was to investigate whether the dependency of midlife stroke survivors had any long-term impact on their spouses' QALY-weights. METHOD: Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. Health-related quality of life was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. Spouses of dependent and independent stroke survivors were categorized according to their scores on the modified Rankin Scale. An ordinary least squares regression analysis was used to evaluate whether the dependency of the stroke survivors had any impact on the spouses' QALY-weights. RESULT: Cohabitant dyads of 247 stroke survivors aged <70 at stroke onset and 245 dyads of controls were included in the study. Spouses of dependent stroke survivors (n = 50) reported a significant lower mean QALY-weight of 0.69 in comparison to spouses of independent stroke survivors (n = 197) and spouses of controls, (n = 245) who both reported a mean QALY-weight of 0.77. The results from the regression analysis showed that higher age of the spouse and dependency of the stroke survivor had a negative association with the spouses' QALY-weights. CONCLUSION: The QALY-weights for spouses of dependent midlife stroke survivors were significantly reduced compared to spouses of independent midlife stroke survivors. This indicates that the inclusion of spouses' QALYs in evaluations of early treatment and rehabilitation efforts to reduce stroke patients' dependency would capture more of the total effect in dyads of stroke survivors.

Low Circulating Acute Brain-Derived Neurotrophic Factor Levels Are Associated With Poor Long-Term Functional Outcome After Ischemic Stroke.

BACKGROUND AND PURPOSE: Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair, and it influences stroke outcomes in animal models. Circulating BDNF concentrations are lowered in patients with traumatic brain injury, and low BDNF predicts poor recovery after this injury. We sought to investigate whether circulating concentrations of BDNF are altered in the acute phase of ischemic stroke and whether they are associated with short- or long-term functional outcome. METHODS: Serum concentrations of BDNF were measured in the Sahlgrenska Academy Study on Ischemic Stroke. The main outcomes were modified Rankin Scale (mRS) good (mRS score of 0-2) versus poor (mRS score of 3-6) at 3 months and 2 years after stroke, and good (mRS score of 0-2) versus poor (mRS score of 3-5) at 7 years after stroke. RESULTS: Acute concentrations of BDNF were significantly lower in ischemic stroke cases (n=491) compared with controls (n=513). BDNF concentrations were not significantly associated with 3-month outcome. However, patients with BDNF in the lowest tertile had an increased risk of experiencing a poor outcome both at 2-year and 7-year follow-up, and these associations were independent of vascular risk factors and stroke severity (odds ratio, 2.6; confidence intervals, 1.4-4.9; P=0.002 and odds ratio, 2.1; confidence intervals, 1.1-3.9; P=0.028, respectively). CONCLUSIONS: Circulating concentrations of BDNF protein are lowered in the acute phase of ischemic stroke, and low levels are associated with poor long-term functional outcome. Further studies are necessary to confirm these associations and to determine the predictive value of BDNF in stroke outcomes.

The High Prevalence of Anxiety Disorders After Stroke.

OBJECTIVES: Previous studies indicate that post-stroke anxiety is common and persistent. We aimed to determine whether point prevalence of anxiety after stroke is higher than in the population at large, and whether the profile of anxiety symptoms is different. METHODS: This case-control study was conducted in Göteborg, Sweden, with stroke patients recruited from the Sahlgrenska University Hospital and a comparison group selected from local population health studies. We included 149 stroke survivors (assessed at 20 months post-stroke) and 745 participants from the general population matched for age and sex. A comprehensive psychiatric interview was conducted, with anxiety and depressive disorders diagnosed according to DSM-III-R criteria. RESULTS: Those in the stroke group were significantly more likely than those in the comparison group to have generalized anxiety disorder (GAD) (27% versus 8%), phobic disorder (24% versus 8%) and obsessive-compulsive disorder (9% versus 2%). Multivariate regression indicated that being in the stroke group, female sex, and having depression were all significant independent associates of having an anxiety disorder. In terms of symptom profile, stroke survivors with GAD were significantly more likely to report vegetative disturbance than those in the comparison group with GAD but less likely to have observable muscle tension or reduced sleep. CONCLUSIONS: Point prevalence of anxiety disorders is markedly higher after stroke than in the general population, and this cannot be attributed to higher rates of comorbid depression.

Living alone predicts mortality in patients with ischemic stroke before 70 years of age: a long-term prospective follow-up study.

BACKGROUND: Living alone is associated with increased mortality after myocardial infarction but little data is available about whether this applies to prognosis after stroke. We aimed to examine the association between living situation and long-term mortality in patients with ischemic stroke and a control group, and to explore whether this association is modified by patient gender. METHODS: This is a prospective case-control study of 600 patients with ischemic stroke before 70 years of age and 600 age- and sex-matched controls who have been included in the Sahlgrenska Study on Ischemic Stroke. Mortality data were collected through national registers and medical records. We used Cox regression models for identifying predictors of mortality. RESULTS: In the entire sample, mean age was 57 years, proportion of males 64%, proportion living alone 28%, and median follow-up 8.6 years. Mortality rates were 36% among patients living alone, 17% among cohabitant patients, 15% among controls living alone, and 9% among cohabitant controls. Living alone was an independent predictor of all-cause mortality in cases after adjustment for stroke severity, stroke subtype, and vascular risk factors including physical activity, alcohol consumption, and socioeconomic status. A significant interaction was found between gender and living situation; the adjusted hazard ratio for mortality was 3.47 (95% Confidence Interval 2.13-5.65) in male patients living alone, whereas no significant association was observed in women. Living alone was also a predictor of vascular mortality among cases and of all-cause mortality among controls. CONCLUSIONS: Living alone is associated with increased long-term mortality after ischemic stroke in men. Further prospective studies are needed to confirm the observed gender difference and to identify modifiable factors underlying this increased risk.

Spouses of Stroke Survivors Report Reduced Health-Related Quality of Life Even in Long-Term Follow-Up: Results From Sahlgrenska Academy Study on Ischemic Stroke.

BACKGROUND AND PURPOSE: The consequences for the family of stroke survivor are generally studied in a short-term perspective. The aim of this study was to assess long-term aspects of health-related quality of life among spouses of stroke survivors. METHODS: Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The health-related quality of life of spouses was assessed by the Short Form-36, and the characteristics of stroke survivors were assessed using the National Institutes of Health Stroke Scale, the Mini-Mental State Examination, the Hospital Anxiety and Depression Scale, the Barthel Index, and the modified Rankin Scale. RESULTS: Dyads of 248 stroke survivors aged <70 at stroke onset and 245 dyads of matched controls were included. Spouses of stroke survivors and spouses of controls had a median age of 64 and 65, respectively; proportion of men was 35% and 34%, respectively. The spouses of stroke survivors reported lower scores in all the mental domains (P=0.045; P<0.001), as well as in the domains of general health (P=0.013) and physical role (P=0.006), compared with the spouses of controls. Predictors of poor physical health of the spouses were their own age and the level of global disability of the stroke survivor. Predictors of poor mental health of the spouses were depressive symptoms, cognitive impairment, and global disability among the stroke survivors. CONCLUSIONS: The health-related quality of life of spouses of stroke survivors is reduced not only during the first years but also in the long-term perspective.

A history of unemployment or sick leave influences long-term functioning and health-related quality-of-life after severe traumatic brain injury.

PRIMARY OBJECTIVE: The consequences of pre-morbid factors in adults with severe traumatic brain injury have not been widely addressed. This study aimed to determine whether being unemployed or on sick leave before injury influences long-term health-related quality-of-life (HRQoL) and functioning in patients with severe traumatic brain injury. SUBJECTS: Fifty-one consecutive patients were studied; aged 16-65 years, with severe traumatic brain injury who were admitted to Sahlgrenska University Hospital, Gothenburg, from 1999-2002. METHODS: The patients were assessed once, 2-11 years after trauma. Data from the time of injury were combined into a validated prognostic model to adjust for injury severity. Data on sick leave and unemployment before injury were gathered from the Swedish social insurance agency. Outcomes were measured with the Short Form-36 Health Survey, the Glasgow Outcome Scale-Extended, and a self-report questionnaire specifically designed for this study to measure functioning. RESULTS: In a multivariate analysis, a history of sick leave/unemployment predicted a worse long-term global outcome, more problems with personal activities of daily living and worse HRQoL. CONCLUSION: These results should be considered when refining outcome predictions and optimizing rehabilitation interventions for patients with severe traumatic brain injury.

Ten-year mortality after severe traumatic brain injury in western Sweden: a case control study.

PRIMARY OBJECTIVE: Life expectancy may be substantially reduced for many years after severe traumatic brain injury (TBI). This study investigated the patterns of the short- and long-term all-cause mortality and the rates of primary causes of death in patients with severe TBI. SUBJECTS: This study was of 166 consecutive patients (6-82 years) with severe TBI admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, from 1999-2002. The control group consisted of 809 subjects from the community, matched to the TBI cohort for age, gender and postcode area at the time of the injury. METHODS: Survival outcome and cause of death were ascertained 10 years after the injury from the Swedish National Board of Health and Welfare register. The cumulative death rates and causes of death in cases and controls were compared. RESULTS: The risk of death was increased for at least 10 years after severe TBI. The distribution of the causes of deaths differed between cases and controls in the first year of follow-up, but not between 1-year survivors and controls. CONCLUSION: Further research will be required to determine how to improve treatment so as to lower late mortality among survivors of severe TBI.