Reduced long-term mortality after successful resective epilepsy surgery: a population-based study.

BACKGROUND: We investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients. METHOD: Data from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP. RESULTS: SUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic-clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up. CONCLUSIONS: In this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.

Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case-control study.

BACKGROUND: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age. METHODS: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS. RESULTS: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women. CONCLUSIONS: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.

Investigating the Role of Brain Natriuretic Peptide (BNP) and N-Terminal-proBNP in Thrombosis and Acute Ischemic Stroke Etiology.

The need for biomarkers for acute ischemic stroke (AIS) to understand the mechanisms implicated in pathological clot formation is critical. The levels of the brain natriuretic peptides known as brain natriuretic peptide (BNP) and NT-proBNP have been shown to be increased in patients suffering from heart failure and other heart conditions. We measured their expression in AIS clots of cardioembolic (CE) and large artery atherosclerosis (LAA) etiology, evaluating their location inside the clots, aiming to uncover their possible role in thrombosis. We analyzed 80 thrombi from 80 AIS patients in the RESTORE registry of AIS clots, 40 of which were of CE and 40 of LAA etiology. The localization of BNP and NT-BNP, quantified using immunohistochemistry and immunofluorescence, in AIS-associated white blood cell subtypes was also investigated. We found a statistically significant positive correlation between BNP and NT-proBNP expression levels (Spearman's rho = 0.668 p < 0.0001 *). We did not observe any statistically significant difference between LAA and CE clots in BNP expression (0.66 [0.13-3.54]% vs. 0.53 [0.14-3.07]%, p = 0.923) or in NT-proBNP expression (0.29 [0.11-0.58]% vs. 0.18 [0.05-0.51]%, p = 0.119), although there was a trend of higher NT-proBNP expression in the LAA clots. It was noticeable that BNP was distributed throughout the thrombus and especially within platelet-rich regions. However, NT-proBNP colocalized with neutrophils, macrophages, and T-lymphocytes, suggesting its association with the thrombo-inflammatory process.

Risk of poststroke epilepsy after reperfusion therapies: A national cohort study.

BACKGROUND AND PURPOSE: The risk of poststroke epilepsy (PSE) after endovascular treatment (EVT) is not well characterized. In this nationwide study, we assessed the risk of PSE after EVT and identified associated predictors. METHODS: We included all individuals (n = 3319) treated with EVT (±intravenous thrombolysis [IVT]) between 2015 and 2019 in the Swedish National Quality Register for EVT. Two control groups were identified from the Swedish Stroke Register: the first treated with IVT alone (n = 3132) and the second with no treatment (n = 3184), both matched for age, sex, stroke severity, and time of stroke. RESULTS: PSE developed in 7.9% (n = 410). The survival-adjusted 2-year risk was 6.5% (95% confidence interval [CI] = 5.28-7.70) after EVT, 10.0% (95% CI = 8.25-11.75) after IVT, and 12.3% after no revascularization (95% CI = 10.33-14.25). The hazard ratio (HR) of PSE after EVT was almost half compared to no treatment (HR = 0.51, 95% CI = 0.41-0.64). The risk of PSE after EVT was lower compared to no treatment in a multivariable Cox model that adjusted for age, sex, hemicraniectomy, and stroke severity (HR = 0.76, 95% CI = 0.60-0.96). Multivariable predictors of PSE after EVT were large infarction on computed tomography Day 1, high posttreatment National Institutes of Health Stroke Scale score, and need of assistance 3 months after stroke. IVT before EVT was associated with a lower risk of PSE (HR = 0.66, 95% CI = 0.46-0.94). CONCLUSIONS: This nationwide study identified a reduced risk of PSE after EVT. Markers of severe infarction after EVT were associated with PSE, whereas IVT given before EVT was protective.

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke-A Prospective Observational Study.

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p < 0.01), but not in the acute phase after stroke, compared with the controls. Higher acute s-IGFBP-1 was associated with poor functional outcome (mRS score > 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality.

Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVE: To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). METHODS: We prospectively enrolled 347 consecutive patients aged 18 to 49 years with a recent CIS and 347 age- and sex-matched (±5 years) stroke-free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist-to-hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. RESULTS: The screener performance was excellent (Cohen kappa > 0.75) in patients and controls. Compared with nonmigraineurs, any migraine (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.63-3.76) and MA (OR = 3.50, 95% CI = 2.19-5.61) were associated with CIS, whereas MO was not. The association emerged in both women (OR = 2.97 for any migraine, 95% CI = 1.61-5.47; OR = 4.32 for MA, 95% CI = 2.16-8.65) and men (OR = 2.47 for any migraine, 95% CI = 1.32-4.61; OR = 3.61 for MA, 95% CI = 1.75-7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right-to-left shunt in patients with PFO. INTERPRETATION: MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO. ANN NEUROL 2021;89:242-253.

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.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

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.

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

The capacity of neurological pupil index to predict absence of somatosensory evoked potentials after cardiac arrest-A study protocol.

BACKGROUND: Anoxic-ischemic brain injury is the most common cause of death after cardiac arrest (CA). Robust methods to detect severe injury with a low false positive rate (FPR) for poor neurological outcome include the pupillary light reflex (PLR) and somatosensory evoked potentials (SSEP). The PLR can be assessed manually or with automated pupillometry which provides the neurological pupil index (NPi). We aim to describe the interrelation between NPi values and the absence of SSEP cortical response and to evaluate the capacity of NPi to predict the absence of cortical SSEP response in comatose patients after CA. METHODS: A total of 50 patients will be included in an explorative, prospective, observational study of adult (>18 years) comatose survivors of CA admitted to intensive care in a university hospital. NPi assessed with a hand-held pupillometer will be compared to SSEP signals recorded >48 hours after CA. Primary outcomes are sensitivity, specificity, and odds ratio for NPi to predict bilateral absence of the SSEP N20 signal, with NPi values corresponding to <5% FPRs of SSEP absence. Secondary outcomes are the PLR and SSEP sensitivity, specificity, and odds ratio for poor neurological outcome at hospital discharge and death at 30 days. DISCUSSION: The PLR and SSEP may have a systematic interrelation, and a certain NPi threshold could potentially predict the absence of cortical SSEP response. If this can be concluded from the present study, SSEP testing could be excluded in certain patients to save resources in the multimodal prognostication after CA. Editorial comment The interrelation between loss of the pupillary light reflex (PLR) and the loss of cortical response to a somatosensory evoked potential (SSEP) in comatose cardiac arrest patients is not known. This exploratory prospective study is designed to evaluate whether a specific degree of attenuated PLR, as measured by semiautomated pupillometry, can predict the bilateral loss of cortical SSEP response in severe anoxic/ischemic brain injury. Such an interrelation between the two methods would enable the use of pupillometry rather than the more resource demanding SSEP for neurologic prognostication in post cardiac arrest patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04720482, Registered 21 January 2021, retrospectively registered.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

OBJECTIVES: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. MATERIALS AND METHODS: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. RESULTS: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. CONCLUSIONS: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.

OBJECTIVES: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization. MATERIALS AND METHODS: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3. RESULTS: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm2, Cardioembolic=52 mm2, Cryptogenic=47 mm2 and Other=52 mm2 (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups. CONCLUSION: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.

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.

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.

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.

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.