Transient cognitive impairment in the acute phase of stroke - prevalence, risk factors and influence on long-term prognosis in population of patients with stroke (research study - part of the PROPOLIS study).

BACKGROUND: Cognitive impairment is a common complication of the acute phase of stroke, which can be transient and resolve while still in the hospital. This study evaluated the prevalence and risk factors for transient cognitive impairment and their impact on long-term prognosis in a population of acute-phase stroke patients. METHODS: Consecutive patients admitted to a stroke unit with acute stroke or transient ischemic attack were screened twice for cognitive impairment using the parallel version of Montreal Cognitive Assessment: the first time between the first and third day and the second time between the fourth and seventh day of hospitalization. If the second test score increased by two or more points, transient cognitive impairment was diagnosed. Patients were scheduled for follow-up visits three and 12 months after stroke. Outcome assessment included place of discharge, current functional status, dementia, or death. RESULTS: Four hundred forty-seven patients were included in the study, 234 (52.35%) were diagnosed with transient cognitive impairment. Delirium was the only independent risk factor for transient cognitive impairment (OR 2.417, 95%CI 1.096-5.333, p = 0.029). In the analysis of effects on three- and twelve-month prognosis, patients with transient cognitive impairment had a lower risk of hospital or institution stay 3 months after stroke compared with patients with permanent cognitive impairment (OR 0.396, 95%CI 0.217-0.723, p = 0.003). There was no significant effect on mortality, disability or risk of dementia. CONCLUSIONS: Transient cognitive impairment, which often occurs in the acute phase of stroke, does not increase the risk of long-term complications.

Elevated plasma levels of galectin-3 binding protein are associated with post-stroke delirium - A pilot study.

To explore the role of systemic inflammation in post-stroke delirium, we investigated the level of two inflammatory mediators: high mobility group box 1 (HMGB1) and galectin-3 binding protein (Gal-3BP). Of 571 stroke patients, we compared plasma levels of HMGB1 and Gal-3BP in 79 delirious patients with 81 non-delirious patients matched for age and stroke severity. Delirious patients had higher Gal-3BP level (median: 1440 vs 1053 ng/mL, P < 0.01). An elevated level of Gal-3BP was associated with an increased risk of delirium. HMGB1 levels did not differ between groups. Our results suggest that pro-inflammatory monocytes and macrophages might be involved in delirium pathophysiology.

Early Depression Independently of Other Neuropsychiatric Conditions, Influences Disability and Mortality after Stroke (Research Study-Part of PROPOLIS Study).

Post-stroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. The nature of the relationship between PSD and mortality still remains unknown. One hypothesis is that PSD could be more frequent in those patients who are more vulnerable to physical disability, a mediator variable for higher level of physical damage related to higher risk of mortality. Therefore, the authors' objective was to explore the assumption that PSD increases disability after stroke, and secondly, that mortality is higher among patients with PSD regardless of stroke severity and other neuropsychiatric conditions. We included 524 consecutive patients with acute stroke or transient ischemic attack, who were screened for depression between 7-10 days after stroke onset. Physical impairment and death were the outcomes measures at evaluation check points three and 12 months post-stroke. PSD independently increased the level of disability three (OR = 1.94, 95% CI 1.31-2.87, p = 0.001), and 12 months post-stroke (OR = 1.61, 95% CI 1.14-2.48, p = 0.009). PSD was also an independent risk factor for death three (OR = 5.68, 95% CI 1.58-20.37, p = 0.008) and 12 months after stroke (OR = 4.53, 95% CI 2.06-9.94, p = 0.001). Our study shows the negative impact of early PSD on the level of disability and survival rates during first year after stroke and supports the assumption that depression may act as an independent mediator for disability leading to death in patients who are more vulnerable for brain injury.

Delirium Post-Stroke-Influence on Post-Stroke Dementia (Research Study-Part of the PROPOLIS Study).

BACKGROUND: Previous research confirmed association between delirium and subsequent dementia in different clinical settings, but the impact of post-stroke delirium on cognitive functioning is still under-investigated. Therefore, we aimed to assess the risk of dementia among patients with stroke and in-hospital delirium. METHODS: A total of 750 consecutive patients admitted to the stroke unit with acute stroke or transient ischemic attacks were screened for delirium, during the first seven days after admission. At the three- and twelve-month follow-up, patients underwent cognitive evaluation. The DSM-5 definition for dementia was used. Cases with pre-stroke dementia were excluded from the analysis. RESULTS: Out of 691 included cases, 423 (61.22%) and 451 (65.27%) underwent cognitive evaluation, three and twelve months after stroke; 121 (28.61%) and 151 (33.48%) patients were diagnosed with dementia, respectively. Six (4.96%) patients with dementia, three months post-stroke did not meet the diagnostic criteria for dementia nine months later. After twelve months, 37 (24.50%) patients were diagnosed with dementia, first time after stroke. Delirium in hospital was an independent risk factor for dementia after three months (OR = 7.267, 95%CI 2.182-24.207, p = 0.001) but not twelve months after the stroke. CONCLUSIONS: Patients with stroke complicated by in-hospital delirium are at a higher risk for dementia at three but not twelve months post-stroke.

Delirium Post-Stroke: Short- and Long-Term Effect on Depression, Anxiety, Apathy and Aggression (Research Study-Part of PROPOLIS Study).

BACKGROUND: Stroke patients are particularly vulnerable to delirium episodes, but very little is known about its subsequent adverse mental health outcomes. The author's objective was to explore the association between in-hospital delirium and depression, anxiety, anger and apathy after stroke. METHODS: A total of 750 consecutive patients with acute stroke or transient ischemic attack, were screened for delirium during hospitalization. Patients underwent mental health evaluation in hospital, 3 and 12 months post-stroke; depression, apathy, anxiety and anger were the outcomes measured at all evaluation check points. RESULTS: Delirium was an independent risk factor for depression (OR = 2.28, 95%CI 1.15-4.51, p = 0.017) and aggression (OR = 3.39, 95%CI 1.48-7.73, p = 0.004) at the hospital, for anxiety 3 months post-stroke (OR = 2.83, 95%CI 1.25-6.39, p = 0.012), and for apathy at the hospital (OR = 4.82, 95%CI 2.25-10.47, p < 0.001), after 3 (OR = 3.84, 95%CI 1.31-11.21, p = 0.014) and 12 months (OR = 4.95, 95%CI 1.68-14.54, p = 0.004) post stroke. CONCLUSIONS: The results of this study confirm, that mental health problems are very frequent complications of stroke. Delirium in the acute phase of stroke influences mental health of patients. This effect is especially significant in the first months post-stroke and vanishes with time, which suggests that in-hospital delirium might not be a damaging occurrence in most measures of mental health problems from a long-term perspective.

C-reactive protein and post-stroke depressive symptoms.

Our study aimed to explore the association between serum C-reactive protein (CRP) and post-stroke depressive symptoms. We prospectively recruited 572 patients with ischemic stroke or transient ischemic attack in whom serum CRP level was measured within 48 h after stroke onset. Depressive symptoms were assessed at day 8 and 3 months after stroke in 405 and 306 patients, respectively. Patients with greater depressive symptoms at day 8 and patients with greater depressive symptoms 3 months after stroke had higher CRP level (median: 7.9 vs 4.3 mg/L, P < 0.01 and 6.7 vs 3.4 mg/L, P = 0.01, respectively). In the univariate analysis, CRP > 9.2 mg/L was associated with depressive symptoms at day 8 (OR: 2.06, 95%CI: 1.30-3.28, P < 0.01) and CRP > 4.3 mg/L was associated with depressive symptoms 3 months after stroke (OR: 1.79, 95%CI: 1.06-3.02, P = 0.03). In the multivariate analysis, higher CRP level was related to depressive symptoms at day 8 (OR: 2.23, 95%CI: 1.28-3.90, P < 0.01), but not depressive symptoms 3 months after stroke (OR: 1.13, 95%CI: 0.59-2.17, P = 0.71). In conclusion, higher levels of CRP are associated with greater depressive symptoms at day 8 after stroke, but their effects on depressive symptoms 3 months after stroke are less significant.

The long-term prognosis of patients with delirium in the acute phase of stroke: PRospective Observational POLIsh Study (PROPOLIS).

BACKGROUND AND PURPOSE: Delirium is a very common neurobehavioral complication after stroke, but its influence on long-term outcome is not well characterized. The objective of the study was to determine the prognostic significance of delirium for functional status, nursing home admission, and mortality in a large cohort of patients with delirium in the acute phase of stroke assessed 3 and 12 months after stroke. METHODS: All stroke survivors included in PROPOLIS were followed up (n = 682). Outcome data included: discharge destination, recurrence of stroke, cardiovascular complications, functional activity and mobility, nursing home admission, and mortality. RESULTS: Patients with delirium were discharged to another hospital or nursing home significantly more often than those presenting without delirium. The 3- and 12-month post-stroke mortality rates were higher in delirious patients (OR 6.41 CI 3.76-10.92; p < 0.001 and OR 5.17 CI 3.36-7.96; p < 0.001). When considering 3-month mortality, higher age, modified Rankin Scale prior to admission and temperature between 1 and 3 days after admission, as well delirium, pneumonia and more severe neurological deficits on admission were independent risk factors. For 12-month mortality, the independent risk factors were higher age and modified Rankin Scale post-stroke, delirium, and history of respiratory diseases prior to stroke. Patients with delirium were more likely to live in nursing homes 3 and 12 months after stroke and were more disabled than patients without delirium. CONCLUSIONS: Delirium in acute phase of stroke negatively influences the long-term prognosis. A study addressing the effect of early recognition and treatment of identified modifiable risk factors for adverse long-term outcomes is urgently needed to decrease bad prognosis within this population.

Poststroke Delirium Clinical Motor Subtypes: The PRospective Observational POLIsh Study (PROPOLIS).

OBJECTIVE: Although delirium is the most common neurobehavioral complication after stroke, its motor subtypes-hypoactive, hyperactive, mixed, and none-as well as their risk factors are not well characterized. Motor subtypes influence recognition and prognosis of delirium in hospitalized patients. METHODS: The aim of this prospective study was to assess the frequency of poststroke delirium subtypes and to describe their predictive models. Consecutive patients with stroke were screened for delirium with the Confusion Assessment Method for the Intensive Care Unit. Delirium was diagnosed according to DSM-5 criteria, and subtypes were classified with the Delirium Motor Subtype Scale-4. Baseline demographic characteristics, biochemistry, stroke-related data, medications, neurological deficits, and premorbid cognitive and functional impairments were assessed. RESULTS: Out of 750 patients (mean age, 71.75 years [SD=13.13]), 203 (27.07%) had delirium: 85 (11.34%) were hypoactive, 77 (10.27%) were mixed hypoactive-hyperactive, 31 (4.13%) were hyperactive, and 10 (1.33%) had an unspecified type. Cognitive impairment at the time of hospital admission and spatial neglect, among other factors, were identified as the best predictors for all motor delirium subtypes. CONCLUSIONS: Screening for poststroke delirium is important because the hypoactive subtype bears the worst prognosis and is misdiagnosed the most compared with other subtypes. All identified factors for the predictive models of delirium subtypes are routinely assessed during hospital admission. Their occurrence in patients with stroke should alert the treating physician to the high risk for a particular delirium subtype.

The association between plasma endotoxin, endotoxin pathway proteins and outcome after ischemic stroke.

BACKGROUND AND AIMS: In animals, peripheral lipopolysaccharide (LPS) injection before cerebral ischemia exacerbates neurological deficit, impairs survival and augments sickness behaviour. The goal of our study was to determine a relationship between plasma LPS, LPS pathway proteins (LPS binding protein (LBP) and sCD14) and outcome in stroke patients. METHODS: We included 335 patients with ischemic stroke. Plasma LPS activity and levels of LBP and sCD14 were measured within 24 h after stroke onset. The endpoints of this study were (1) 3-month poor functional outcome defined as a modified Rankin Scale score >2; (2) 3-month and 12-month case fatality; (3) delirium during the first 7 days after admission. RESULTS: Plasma LPS activity did not correlate with either functional outcome or mortality. The higher levels of LBP and sCD14 predicted 3-month and 12-month case fatality. The adjusted hazard ratio for 12-month case fatality was 1.84 (95% CI: 1.32-2.58, p < 0.01) for LBP and 1.62 (95% CI: 1.15-2.29, p < 0.01) for sCD14. On multivariate analysis, higher LPS activity (OR: 1.63, 95% CI: 1.15-2.31, p = 0.01) and higher LBP (OR: 1.44, 95% CI: 1.04-2.00, p = 0.03) and sCD14 levels (OR: 1.54, 95% CI: 1.12-2.13, p = 0.01) were associated with increased risk of delirium. CONCLUSIONS: In ischemic stroke patients, higher levels of plasma sCD14 and LBP are associated with increased risk of death, whereas, elevated LPS activity and higher levels of LBP and CD14 are associated with post-stroke delirium.

Reduced release of TNFα and IP-10 after ex vivo blood stimulation with endotoxin is associated with poor outcome after stroke.

BACKGROUND AND AIMS: The immune response to acute cerebral ischemia plays an important role in the pathophysiology of stroke and could be a therapeutic target. Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of our study was to determine the association between selected cytokine release after TLR4 activation in blood cells and the outcome after ischemic stroke. METHODS: We included 156 ischemic stroke patients (median age: 69; 40.4% female). Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). The LPS-induced level of tumor necrosis factor alpha (TNFα) was used as a proxy of the MyD88-dependent pathway, and interferon-gamma-inducible protein 10 (IP-10) was used as a proxy of the MyD88-independent pathway. The functional outcome was assessed at 3 months after stroke onset. RESULTS: TNFα (median: 2.2 vs. 3.5 pg/103 monocytes, p < .01) and IP-10 release (median: 0.3 vs. 0. 6 pg/103 monocytes, p < .01) was reduced in patients with a poor outcome. In a multivariate logistic regression analysis adjusted for age, stroke severity, and pneumonia, low TNFα release was associated with a poor outcome (OR: 4.23, 95%CI: 1.64-10.90, p = .03). Similarly, low IP-10 release was related to an unfavorable prognosis (adjusted OR: 3.42, 95%CI: 1.49-8.21, p < .01). CONCLUSIONS: The reduced release of TNFα and IP-10 after ex vivo blood stimulation with endotoxin is independently associated with poor outcome after stroke. Our results suggest that the inhibition of both the MyD88-dependent pathway and MyD88-independent pathway of TLR4 signaling in blood cells correlates with an unfavorable prognosis in stroke patients.

Pre-stroke apathy symptoms are associated with an increased risk of delirium in stroke patients.

Neuropsychiatric symptoms can be interrelated to delirium. We aimed to investigate an association between pre-stroke neuropsychiatric symptoms and the risk of delirium in stroke patients. We included 606 patients (median age: 73, 53% female) with stroke or transient ischemic attack admitted within 48 hours from symptoms onset. We assessed delirium on a daily basis during the first 7 days of hospitalization. To make diagnosis of delirium we used DSM-5 criteria. We used Neuropsychiatric Inventory to assess neuropsychiatric symptoms occurring within 4 weeks prior to stroke. We diagnosed delirium in 28.2% of patients. On univariate analysis, higher score of pre-stroke depression (OR: 1.58, 95% CI: 1.04-2.40, P = 0.03), apathy (OR: 2.23, 95% CI: 1.44-3.45, P < 0.01), delusions (OR: 2.00, 95% CI: 1.09-3.68, P = 0.03), hallucinations (OR: 2.39, 95% CI: 1.19-4.81, P = 0.01) and disinhibition (OR: 2.10, 95% CI: 1.04-4.25, P = 0.04) was associated with the increased risk of delirium. On multivariate analysis adjusted for age, atrial fibrillation, diabetes mellitus, stroke severity, right hemisphere lesion, pre-stroke cognitive decline, pre-stroke disability and infections, higher apathy score (OR: 2.03, 95% CI: 1.17-3.50, P = 0.01), but no other neuropsychiatric symptoms, remained independent predictor of delirium. We conclude that pre-stroke apathy symptoms are associated with increased risk of delirium in stroke patients.