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.

Reduced ex vivo release of pro-inflammatory cytokines and elevated plasma interleukin-6 are inflammatory signatures of post-stroke delirium.

BACKGROUND: Experimental studies suggest that systemic inflammation contributes to the pathophysiology of delirium. The aim of our study was to determine blood-derived inflammatory signatures of post-stroke delirium. METHODS: We included 144 ischemic stroke patients. We assessed delirium on a daily basis during the first 7 days of hospitalization. Venous blood was collected at day 3 after the onset of stroke and stimulated ex vivo with lipopolysaccharide (LPS). We measured LPS-induced cytokine concentration (TNFα, IP-10, IL-1ß, IL-6, IL-8, IL-10, and IL-12p70) as well as plasma levels of IL-6 and TNFα. RESULTS: Delirium was diagnosed in 21.5% of patients. After correction for monocyte count, patients with delirium had reduced LPS-induced TNFα, IP-10, IL-1ß, IL-6, and IL-12 release. The plasma IL-6 level was higher in delirious patients compared to patients without delirium. After adjusting for stroke severity and infections, higher ex vivo TNFα (OR 0.29, 95%CI 0.11-0.72, P = 0.01), IP-10 (OR 0.25, 95%CI 0.08-0.73, P = 0.01), IL-1ß (OR 0.42, 95%CI 0.20-0.89, P = 0.02), and IL-12 (OR 0.07, 95%CI 0.01-0.70, P = 0.02) release was associated with the reduced risk of delirium. In multivariate analysis, the higher plasma IL-6 was associated with the increased risk of delirium (OR 1.61, 95%CI 1.00-2.58, P = 0.04). CONCLUSIONS: Reduced ex vivo release of pro-inflammatory cytokines after LPS stimulation and the elevated plasma IL-6 are signatures of post-stroke delirium.

Thymus imaging in myasthenia gravis: The relevance in clinical practice.

INTRODUCTION: The ability to distinguish between normal thymus, thymic hyperplasia, and thymoma should aid clinical management and decision making in patients with myasthenia gravis (MG). We sought to determine the accuracy of routine imaging in predicting thymic pathology. METHODS: We retrospectively analyzed records of patients with MG from the Oxford Myasthenia Centre registry who had undergone thymectomy. Each patient received 1 radiological diagnosis and 1 histological diagnosis. RESULTS: We included 106 patients. Radiological and histological diagnoses agreed in 73 (68.9%) patients. Sensitivity and specificity, respectively, were calculated for each radiological diagnosis as follows: thymoma 90% and 95.5%, hyperplasia 17.6% and 98.6%, and normal 96.9% and 60.8%. DISCUSSION: Routine chest computed tomography and MRI can effectively identify thymoma. However, they are not reliable tools to differentiate between thymic hyperplasia and normal thymus in patients with MG. Muscle Nerve, 2018.

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.

Knowns and Unknowns About Delirium in Stroke: A Review.

Delirium is a transient condition characterized by sudden and fluctuating disturbances in cognitive function. The condition can be considered a sign of the brain's vulnerability and diminished resilience to insult. Among the many clinical manifestations are cognitive, psychomotor, and sleep disturbances. Delirium is associated with longer hospital stays, worse functional outcomes, and higher mortality. Although up to 48% of patients who have had a stroke develop delirium, the condition has been studied much less in these patients than in general medicine, surgical, and intensive care patients. Coexisting neurologic deficits in patients with stroke limit the use of screening tools that are widely accepted in other populations. The variability of reported assessment methods highlights the need for delirium screening guidelines in stroke. Further, risk factors that are specific to stroke may play an important role in the etiology of delirium, along with such well-known factors as older age and infections. The delirium literature lacks data on differences in clinical manifestations and course in the various types of stroke. Here we review predisposing factors, diagnostic methods, and biomarkers of delirium in stroke and discuss aspects that need further research.

Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome.

BACKGROUND: Activation of Toll-like receptor 4 (TLR4) contributes to brain injury and poor outcome after cerebral ischemia. The expression of this receptor on monocytes is increased in patients with acute ischemic stroke. Endotoxin is an endogenous ligand for TLR4. The aim of our study was to determine if plasma endotoxin activity is increased in stroke patients and correlates with functional outcome. METHODS: We included 88 patients with ischemic stroke (median age: 71, 56.8% men) and 59 age-matched controls. Plasma endotoxin activity and level of proteins regulating endotoxin interaction with TLR4 (LPS binding protein - LBP and sCD14) were measured in blood samples taken at day 1 (within 24h after stroke symptoms onset), 3 and 6. Short-term functional outcome was assessed at day 14 using modified Rankin Scale. Unfavourable outcome was defined as modified Rankin Scale score>2. RESULTS: Compared to controls, stroke patients had higher plasma endotoxin activity on day 1 (median: 0.39 vs 0.32EU/mL, P=0.03) as well as higher LBP (median: 18.7 vs 11.5µg/mL, P<0.01) and sCD14 level (median: 1330 vs 1070ng/mL, P<0.01). Plasma LPS activity and levels of LBP and sCD14 significantly rose during stroke. Higher LPS activity measured on day 6 was associated with unfavourable outcome (OR: 3.94, 95%CI: 1.03-15.02, P=0.04, adjusted for age and stroke severity). CONCLUSIONS: Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome.

Mild Cognitive Impairment as a single sign of brain hemiatrophy in patient with Localized Scleroderma and Parry-Romberg Syndrome.

Neurologic involvement is well recognized in Systemic Scleroderma and increasingly reported in Localized Scleroderma. MRI brain abnormalities are often associated with symptoms such as seizures or headaches. In some cases they may be clinically silent. We describe a 23 years old female with head, trunk and limbs scleroderma who developed Parry-Romberg Syndrome. Brain MRI showed ipsilateral temporal lobe atrophy without any prominent neurologic symptoms. Neuropsychological examination revealed Mild Cognitive Impairment. During the 7 years of follow up we have noticed progression of face atrophy but no progression of brain atrophy. Cognitive functions have been stable. This case highlight that major MRI brain abnormalities in LS may occur with only subtle clinical manifestation such as Mild Cognitive Impairment.

PRospective Observational POLIsh Study on post-stroke delirium (PROPOLIS): methodology of hospital-based cohort study on delirium prevalence, predictors and diagnostic tools.

BACKGROUND: Between 10 % to 48 % of patients develop delirium in acute phase of stroke. Delirium determinants and its association with other neuropsychiatric disturbances in stroke are poorly understood. The wildly accepted predictive model of post-stroke delirium is still lacking. METHODS/DESIGN: This is a prospective, observational, single-center study in patients with acute phase of stroke. We aim to include 750 patients ≥18 years with acute stroke or transient ischemic attack admitted to the stroke unit within 48 hours after stroke onset. The goals of the study are: 1) to determine frequency of delirium and subsyndromal delirium in Polish stroke patients within 7 days after admission to the hospital; 2) to determine factors associated with incidence, severity and duration of delirium and subsyndromal delirium and to create a predictive model for post-stroke delirium; 3) to determine the association between delirium and its cognitive, psychiatric, behavioral and functional short and long-term consequences; 4) to validate scales used for delirium diagnosis in stroke population. Patients will be screened for delirium on daily basis. The diagnosis of delirium will be based on DSM-V criteria. Abbreviated version of Confusion Assessment Method and Confusion Assessment Method for the Intensive Care Unit will be used for delirium and sub-delirium screening. Severity of delirium symptoms will be assessed by Delirium Rating Scale Revised 98 and Cognitive Test for Delirium. Patients who survive will undergo extensive neuropsychological, neuropsychiatric and functional assessment 3 and 12 months after the stroke. DISCUSSION: This study is designed to provide information on clinical manifestation, diagnostic methods and determinants of delirium spectrum disorders in acute stroke phase and their short and long-term consequences. Collected information allow us to create a predictive model for post-stroke delirium.