Gene expression profiling in whole blood stimulated ex vivo with lipopolysaccharide as a tool to predict post-stroke depressive symptoms: Proof-of-concept study.

Prediction of post-stroke depressive symptoms (DSs) is challenging in patients without a history of depression. Gene expression profiling in blood cells may facilitate the search for biomarkers. The use of an ex vivo stimulus to the blood helps to reveal differences in gene profiles by reducing variation in gene expression. We conducted a proof-of-concept study to determine the usefulness of gene expression profiling in lipopolysaccharide (LPS)-stimulated blood for predicting post-stroke DS. Out of 262 enrolled patients with ischemic stroke, we included 96 patients without a pre-stroke history of depression and not taking any anti-depressive medication before or during the first 3 months after stroke. We assessed DS at 3 months after stroke using the Patient Health Questionnaire-9. We used RNA sequencing to determine the gene expression profile in LPS-stimulated blood samples taken on day 3 after stroke. We constructed a risk prediction model using a principal component analysis combined with logistic regression. We diagnosed post-stroke DS in 17.7% of patients. Expression of 510 genes differed between patients with and without DS. A model containing 6 genes (PKM, PRRC2C, NUP188, CHMP3, H2AC8, NOP10) displayed very good discriminatory properties (area under the curve: 0.95) with the sensitivity of 0.94 and specificity of 0.85. Our results suggest the potential utility of gene expression profiling in whole blood stimulated with LPS for predicting post-stroke DS. This method could be useful for searching biomarkers of post-stroke depression.

Serum C-reactive protein adds predictive information for post-stroke delirium: The PROPOLIS study.

OBJECTIVE: Delirium is common and serious complication after stroke. Accurate prediction of delirium is important for prevention and monitoring of high-risk patients. Our study aimed to determine if addition of C-reactive protein (CRP) to a model based on easy-to-access clinical predictors improves accuracy of delirium prediction in acute stroke patients. METHODS: We analyzed data of patients participating in the Prospective Observational Polish Study on post-stroke delirium. We included patients admitted within 24 h after stroke or transient ischemic attack (TIA) in whom serum CRP was measured on admission. We examined core features of delirium during first 7 days of hospitalization. We assessed if addition of CRP to two clinical models improved metrics of discrimination and reclassification. Model A included age and stroke severity and Model B included stroke severity, atrial fibrillation, diabetes mellitus, pre-stroke dependency, and hemorrhagic stroke. RESULTS: We included 459 patients. We diagnosed delirium in 29.2% of them. Patients who developed delirium had higher CRP level than those without delirium (median: 13.2 vs. 4.4 mg/L, p < 0.001). CRP >7.09 mg/L was associated with an increased risk of delirium (adjusted OR: 2.98, 95%CI: 1.71-5.19, p < 0.001). After adding CRP to clinical models, an area under receiver operator curve increased from 0.77 to 0.80 (p = 0.038) for Model A and from 0.81 to 0.84 (p = 0.016) for Model B. There was also improvement in reclassification. CONCLUSIONS: Addition of CRP to clinical predictors moderately improved prediction of post-stroke delirium. CRP could be considered as a potential biomarker to stratify risk of delirium after stroke.

Pre-stroke and early post-stroke apathy is associated with increased risk of dementia 3 months after stroke.

OBJECTIVES: Apathy is a frequent neuropsychiatric syndrome after stroke. We determined whether pre-morbid and early post-stroke apathy predicts dementia 3 months after stroke. METHODS: We included ischemic stroke patients without dementia who participated in the Prospective Observational Polish Study on post-stroke delirium. We used the Neuropsychiatric Inventory and clinician-reported version of Apathy Evaluation Scale to score apathy symptoms before stroke and on day 8 after stroke. Patients underwent neuropsychological examination 3 months after stroke. RESULTS: Of 422 patients with ischemic stroke and without pre-stroke dementia, 194 patients (mean age: 67.5 ± 12.3; 45.9% female) underwent neuropsychological examination. Dementia was diagnosed in 21.6% of them. Patients with dementia had higher apathy scores before stroke (mean: 0.9 ± 1.7 vs. 0.2 ± 0.9, p < 0.01) and on day 8 (mean: 37.2 ± 9.3 vs. 29.0 ± 9.6, p < 0.01). Depressive symptoms did not differ between groups. In multivariate analysis adjusted for age, diabetes mellitus, stroke severity and in-hospital delirium, apathy symptoms before stroke and on day 8 after stroke predicted post-stroke dementia (adjusted OR: 1.59, 95%CI: 1.13-2.26, p = 0.01 and OR: 1.06, 95%CI: 1.01-1.11, p = 0.03, respectively). CONCLUSIONS: Pre-stroke and early post-stroke apathy independently from age, stroke severity and delirium predicted dementia 3 months after stroke. Apathy might be useful in identifying at-risk patients.

Subtypes of delirium after ischaemic stroke-predisposing factors and outcomes: a prospective observational study (PROPOLIS).

BACKGROUND AND PURPOSE: Delirium is a serious complication after stroke. It remains unclear whether different motor subtypes of delirium are associated with diverse risk factors and outcomes. The aim was to investigate if delirium subtypes differ in predisposing factors, clinical characteristics and outcomes. METHODS: In all, 698 patients with ischaemic stroke or transient ischaemic attack (median age 73 years; 53.7% female) were prospectively included. Core features of delirium during the first 7 days after admission were examined. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for delirium were used. Pre-stroke characteristics were compared between different delirium subtypes and logistic regression and Cox proportional hazard models were used to explore the association between delirium, functional outcome and death. RESULTS: Hyperactive, hypoactive and mixed delirium were diagnosed in 28, 75 and 66 patients, respectively. Patients with hyperactive delirium had less severe neurological deficit on admission and more often had transient ischaemic attack compared with patients with hypoactive and mixed delirium. Compared with patients with hypoactive delirium, those with hyperactive delirium more often suffered from irritability/lability prior to stroke. Hyperactive and hypoactive delirium did not differ in age, sex, comorbidities, pre-stroke dependency, cognitive decline and severity of delirium. Hyperactive, hypoactive and mixed delirium were associated with an increased risk of poor 3- and 12-month functional outcome compared with patients without delirium. Moreover, patients with hypoactive and mixed delirium had an elevated risk of death. CONCLUSIONS: Hyperactive delirium is associated with less severe stroke and higher scores of pre-existing irritability/lability. All three motor subtypes of delirium are associated with poor outcome, although hyperactive delirium seems to have a less unfavourable prognosis.

Anatomical aspects of the insula, opercula and peri-insular white matter for a transcortical approach to insular glioma resection.

The insula is a lobe located deep in each hemisphere of the brain and is surrounded by eloquent cortical, white matter, and basal ganglia structures. The aim of this study was to provide an anatomical description of the insula and white matter tracts related to surgical treatment of gliomas through a transcortical approach. The study also discusses surgical implications in terms of intraoperative brain mapping. Five adult brains were prepared according to the Klingler technique. Cortical anatomy was evaluated with the naked eye, whereas white matter dissection was performed with the use of a microscope. The widest exposure of the insular surface was noted through the temporal operculum, mainly in zones III and IV according to the Berger-Sanai classification. By going through the pars triangularis in all cases, the anterior insular point and most of zone I were exposed. The narrowest and deepest operating field was observed by going through the parietal operculum. This method provided a suitable approach to zone II, where the corticospinal tract is not covered by the basal ganglia and is exposed just under the superior limiting sulcus. At the subcortical level, the identification of the inferior frontoocipital fasciculus at the level of the limen insulae is critical in terms of preserving the lenticulostriate arteries. Detailed knowledge of the anatomy of the insula and subcortical white matter that is exposed through each operculum is essential in preoperative planning as well as in the intraoperative decision-making process in terms of intraoperative brain mapping.

The use of anticholinergic medication is associated with an increased risk of stroke-associated pneumonia.

BACKGROUND: Pneumonia is a frequent medical complication after stroke. A few studies showed that the use of anticholinergic medication is associated with a higher risk of community acquired pneumonia in the elderly. We aimed to determine if there is any association between anticholinergic medication used before stroke and stroke-associated pneumonia (SAP). METHODS: We analysed prospectively collected data of 675 patients with acute stroke (mean age 71.4 ± 13.3; 53.1% female). We used the Anticholinergic Drug Scale to assess anticholinergic exposure during a month preceding stroke onset. RESULTS: We diagnosed SAP in 14.7% of patients. The use of anticholinergic medication was associated with an elevated risk of SAP (OR 2.56, 95% CI 1.59-4.11, P < 0.01) in univariate analysis. This association remained significant in multivariable analysis adjusted for age, stroke severity, atrial fibrillation, previous myocardial infarction and respiratory tract diseases (OR 2.06, 95% CI 1.01-4.22, P = 0.04). CONCLUSIONS: The use of anticholinergic medication before stroke is associated with an increased risk of SAP.

Delirium and subsyndromal delirium are associated with the long-term risk of death after ischaemic stroke.

BACKGROUND: Post-stroke delirium has a negative impact on functional outcome. We explored if there is any association between delirium, subsyndromal delirium and long-term mortality after ischaemic stroke and transient ischaemic attack. METHODS: We included 564 patients with ischaemic stroke or transient ischaemic attack. We assessed symptoms of delirium during the first 7 days after admission. We used Cox proportional hazards models to analyse all-cause mortality during the first 5 years after stroke. RESULTS: We diagnosed delirium in 23.4% and subsyndromal delirium in 10.3% of patients. During the follow-up, 72.7% of patients with delirium, 51.7% of patients with subsyndromal delirium and 22.7% of patients without delirious symptoms died (P < 0.001). Patients with subsyndromal delirium and delirium had higher risk of death in the multivariate analysis (HR 1.72, 95% CI 1.11-2.68, P = 0.016 and HR 3.30, 95% CI 2.29-4.76, P < 0.001, respectively). CONCLUSIONS: Post-stroke delirium is associated with long-term mortality. Patients with subsyndromal delirium are at the intermediate risk of death.

Clinical utility of brain computed tomography in prediction of post-stroke delirium.

Delirium is a common and serious complication of stroke. Early prediction of delirium is important for preventive strategies and close monitoring of high-risk patients. Pre-existing degenerative and vascular changes in the brain could predispose to delirium. We aimed to determine if computed tomography (CT)-based indices could provide additional information about a risk of stroke-associated delirium beyond easiest-to-access clinical predictors. Using semi-quantitative scales (global cortical atrophy, age-related white matter changes, and Scheltens scale), we assessed global and regional brain atrophy and white matter changes in 88 stroke patients with delirium and 142 patients without delirium matched for age and stroke severity. Patients with delirium had greater global and local brain atrophy (the right temporal region, the left parieto-occipital region, the right frontal and occipital horn, and the right and left temporal horn) than patients without delirium. Scores of white matter changes did not differ between groups with exception of greater white matter damage in the right parieto-occipital area in patients with delirium. The discriminatory properties of studied radiological indices were modest (areas under receiver operator curves: 0.58-0.64). CT-based indices of brain atrophy and white matter changes do not provide additional information about a risk of post-stroke delirium beyond the most important clinical predictors.

Association of early and later depressive symptoms with functional outcome after ischemic stroke.

BACKGROUND: Post-stroke depressive symptoms (DS) can be chronic or transient, occurring shortly or long after stroke and lasting only few months. It remains unclear if the prognosis differs between patients with DS in the acute phase of stroke and those who develop DS several months later. We aimed to determine whether outcomes vary among patients with different trajectories of post-stroke depressive symptoms. METHODS: Of 698 enrolled patients with ischemic stroke, we included 335 participants (median age: 68, 48% female) who were assessed for DS both 8 days and 3 months post-stroke. We divided patients into 4 groups: without greater DS (Group 1), only earlier DS (Group 2), only later DS (Group 3), and persistent DS (Group 4). Logistic regression was used to determine the association between DS and 3- and 12-month functional outcome. RESULTS: Group 2 was predominantly female and had the highest rate of previous stroke or transient ischemic attack. Group 3 was more likely to suffer from delirium and more severe stroke. Group 4 had the highest frequency of vascular risk factors, pre-morbid psychiatric symptoms, and cognitive decline. In multivariate analysis, Group 3, but not Groups 2 and 4, had an increased risk of poor 3- and 12-month functional outcome (adjusted OR 2.59, 95% CI 1.64-4.07, P < 0.01 and OR 3.97, 95% CI 2.32-6.76, P < 0.01, respectively) compared with Group 1. CONCLUSIONS: Different trajectories of post-stroke DS are related to different outcomes. Patients who only have later DS also have the worst prognosis.

Early apathetic, but not depressive, symptoms are associated with poor outcome after stroke.

BACKGROUND AND PURPOSE: Depression and apathy are frequent neuropsychiatric disturbances after stroke and may appear together. Despite the overlap in symptoms between poststroke depression and apathy, these two syndromes might be associated with different prognoses and benefit from different treatments. We aimed to disentangle the relationship between early depressive and apathetic symptoms and outcome after stroke. METHODS: Of 698 enrolled patients with ischemic stroke, we included 443 participants (median age = 69 years, 51% female) who underwent depressive and apathetic symptom assessment on Day 8 after stroke. We divided patients into four groups: without greater depressive and apathetic symptoms (Group 1), with only apathetic symptoms (Group 2), with only depressive symptoms (Group 3), and with both depressive and apathetic symptoms (Group 4). RESULTS: After adjusting for age and stroke severity, Group 2 and Group 4 had an increased risk of poor 3-month outcome (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.16-3.38, p = 0.01 and OR = 1.58, 95% CI = 1.24-2.01, p < 0.01, respectively). Group 2 and Group 4 also had an increased risk of poor 12-month outcome (OR = 3.85, 95% CI = 2.19-6.78, p < 0.01 and OR = 1.54, 95% CI = 1.22-1.96, p < 0.01, respectively) and mortality (hazard ratio [HR] = 2.76, 95% CI = 1.19-6.41, p = 0.02 and HR = 1.77, 95% CI = 1.32-2.38, p < 0.01, respectively). Compared with Group 1, Group 3 did not have an increased risk of unfavorable outcomes. CONCLUSIONS: Early apathetic, but not depressive, symptoms are related to worse outcomes after stroke. Our study underscores the importance of recognizing apathetic symptoms independently from depressive symptoms.

Magnetisation transfer imaging revealed microstructural changes related to apathy symptoms after ischaemic stroke.

OBJECTIVES: Apathy after stroke is common and has a negative impact on functional recovery. Neuroimaging correlates of poststroke apathy remain unclear. We aimed to investigate microstructural changes associated with the severity of poststroke apathy symptoms. METHODS: We assessed 67 patients with cerebral ischaemia who underwent magnetisation transfer brain imaging 12-15 months after stroke. We used magnetisation transfer ratio (MTR) to represent microstructural integrity. We performed whole-brain voxel-based analysis and subsequent region of interest analysis to investigate the association between MTR and symptoms of poststroke apathy. To assess apathy symptoms, we used clinician-reported version of the Apathy Evaluation Scale. RESULTS: Voxel-based analysis showed the association between symptoms of apathy and decreased MTR in areas overlapping with structures located in both hemispheres: left thalamus, bilateral hippocampus, bilateral fornix/stria terminalis, right amygdala, splenium of the corpus callosum, the retrolenticular part of left internal capsule and left sagittal stratum. In the region of interest analysis, only lower MTR in right fornix/stria terminalis was associated with greater poststroke apathy symptoms in a multivariate logistic model (odds ratio: 1.25, 95% CI: 1.09-1.46, p = 0.003). These associations were independent of depressive symptoms. CONCLUSION: Magnetisation transfer brain imaging 12-15 months after stroke revealed changes in microstructural integrity associated with apathy symptoms in brain areas related to processing emotional information and reward valuation.

Prognostic Significance of Stroke-Associated Infection and other Readily Available Parameters in Acute Ischemic Stroke Treated by Intravenous Thrombolysis.

OBJECTIVES: The impact of contracting stroke-associate infection (SAI) that requires antibiotic treatment after an acute ischemic stroke (AIS) treated with alteplase remains unclear. We studied the profiles of SAI in patients with AIS treated with alteplase toward identifying predictive factors and prognostic implications at 90 days post-stroke. METHODS: We analyzed 33 parameters readily available within 24 hours after AIS: demographics, risk factors, and several clinical and biochemical parameters. Outcome measures were mRS ≤ 2 and mortality 90 days post-stroke. RESULTS: 83 (23.6%) of 352 patients developed SAI. Multivariate logistic regression analysis showed that atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS (the difference between NIHSS score measured upon admission and 24 hours after later), CRP≥10 mg/L, and elevated WBC count affected SAI risk (model including CRP levels and WBC count) and atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS, HT, and elevated fibrinogen levels affected SAI risk (model excluding CRP levels and WBC count). 231 patients (74.1%) had mRS ≤ 2 at day 90. Multivariate logistic regression analysis showed that younger age, no hypertension, mRS=0 pre-stroke, higher delta NIHSS, no HT, no SAI, and CRP<10 mg/L, were associated with mRS≤2 at day 90. 54 (15.3%) patients died within 90 days. Multivariate logistic regression analysis showed that pre-stroke mRS>0, lower delta NIHSS, HT, CRP≥10 mg/L, lower triglyceride levels affected the risk of death within 90 days. CONCLUSIONS: Several markers available within 24 hours post-stroke were predictive of SAI that requires antibiotic treatment. SAI affects long-term outcome but not mortality.

The prognostic significance of large vessel occlusion in stroke patients treated by intravenous thrombolysis.

PURPOSE: According to guidelines, to shorten the treatment window, acute ischaemic stroke (AIS) treatment by intravenous thrombolysis (IVT) can be done based on the results of head computed tomography (CT) without contrast. The impact of large vessel occlusion (LVO) on computed tomography angiography (CTA) in stroke prognosis in patients treated IVT or IVT and mechanical thrombectomy (MT), where indicated, has not yet been studied systematically. We investigated the influence of LVO in consecutive AIS patients on haemorrhagic transformation (HT) on CT 24 h after treatment, mRS < 2 on discharge (unfavourable outcome), and in-hospital mortality. MATERIAL AND METHODS: We analysed several parameters within 24 h after AIS: demographics, risk factors, mRS score pre-stroke, NIHSS upon admission and 24 h later, several clinical and biochemical parameters, and chronic treatment. RESULTS: We registered 1209 patients, of whom 362 (29.9%) received IVT and 108 had MT, where indicated. Admission CTA showed LVO in 197 patients (54.4%). Multivariate regression analysis showed that the presence of LVO and lower delta NIHSS (NIHSS on admission minus NIHSS 24 hours later) were independent parameters affecting HT risk. Multivariate analysis showed that the presence LVO and also older age, female sex, lower delta NIHSS, HT, stroke-associated infection, CRP levels ≥ 10 mg/L, and higher WBC count affected unfavourable outcome on discharge. LVO did not affect in-hospital mortality. CONCLUSIONS: LVO in AIS patients treated by IVT or IVT and MT affects the risk of HT and unfavourable short-term outcome but not in-hospital mortality.

The specific ex vivo released cytokine profile is associated with ischemic stroke outcome and improves its prediction.

BACKGROUND: Inflammation is associated with poor outcome after stroke. A relationship between ex vivo cytokine synthesis and stroke outcome remains unclear. We explored an association between ex vivo cytokine release, circulating interleukin (IL)-6 as a marker of systemic inflammation, and stroke prognosis. We assessed the utility of ex vivo synthesized cytokines for predicting stroke outcome. METHODS: We collected blood from 248 ischemic stroke patients and stimulated it ex vivo with lipopolysaccharide. We measured concentration of synthesized cytokines (TNFα, IP-10, IL-1ß, IL-6, IL-8, IL-10, and IL-12) and plasma IL-6. We assessed functional outcome 3 months after stroke using the modified Rankin Scale. To assess the prognostic ability of cytokines, we applied multivariate logistic regression, cluster analysis, and construction of multimarker score. RESULTS: Decreased release of IP-10, TNFα, IL-1ß, and IL-12; increased release of IL-10 and IL-8; and higher plasma IL-6 level were associated with poor outcome. Cluster analysis identified three groups of patients with distinct cytokine profiles. The group with the worst outcome demonstrated high synthesis of IL-10, IL-8, IL-1ß, and IL-6 and low synthesis of IL-12, IP-10, and TNFα accompanied by high circulating IL-6 level. The group with the best prognosis showed high synthesis of TNFα, IP-10, IL-12, IL-1ß, and IL-6; low synthesis of IL-10 and IL-8; and low plasma IL-6. Patients with intermediate outcome had low synthesis of all cytokines accompanied by low circulating IL-6. We constructed a multimarker score composed of ex vivo released IL-12, IL-10, TNFα, and plasma IL-6. Addition of this score to clinical variables led to significant increase in c-statistic (0.81 vs 0.73, p = 0.02) and net reclassification improvement. CONCLUSION: The decreased ex vivo release of pro-inflammatory cytokines and increased release of IL-10 and IL-8 are related to poor outcome after stroke. Cytokine-based multimarker score adds prognostic value to clinical model for predicting stroke outcome.

Glucocorticoid Resistance is Associated with Poor Functional Outcome After Stroke.

Systemic inflammation is associated with poor outcome after stroke. Glucocorticoids (GCs) play a fundamental role in limiting inflammation. The aim of this study was to explore the associations between GC sensitivity, systemic inflammation, and outcome after ischemic stroke. The study population compised 246 ischemic stroke patients (median age: 69.0 years; 41.1% female). To assess GC sensitivity, we incubated venous blood samples that were obtained at day 3 after stroke with lipopolysaccharide (10 ng/mL) and dexamethasone (10-6 mol/L). We defined the GC sensitivity index as the ratio of tumor necrosis factor α (TNFα) released after blood stimulation with lipopolysaccharide and dexamethasone to the amount of TNFα released after blood stimulation with lipopolysaccharide alone. A higher index indicates higher GC resistance. The patients with poor functional outcome had a higher GC sensitivity index than those with good outcome (median: 16.1% vs. 13.5%, P < 0.01). In a logistic regression analysis adjusted for age, stroke severity, pneumonia, leukocyte count, plasma interleukin-6, and TNFα release ex vivo, a higher GC sensitivity index was associated with a higher risk of poor outcome after stroke (OR 2.32, 95% CI 1.21-4.45, P = 0.01). In conclusion, GC resistance is associated with poor functional outcome after stroke.

Clinical Relevance of Changes in Peripheral Blood Cells After Intracranial Aneurysm Rupture.

BACKGROUND: The rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. We sought to characterize the systemic response to IA rupture. METHODS: We included 19 patients in the acute phase of IA rupture and 20 control subjects. Flow cytometry was used to analyze alterations in the level of mononuclear leukocytes. Cell-related parameters, including the neutrophil-to-lymphocyte ratio (NL-R), lymphocyte-to-monocyte ratio (LM-R), platelet-to-lymphocyte ratio (PL-R), and systemic immune-inflammation index (SII), were calculated, and the relationship between the analyzed hematological parameters and clinical status was investigated. RESULTS: Patients with ruptured IAs presented with significantly higher white blood cells (WBC) and neutrophil counts but lower lymphocyte counts than control subjects. NL-R and SII values were higher and the LM-R was lower in the acute phase after IA rupture. Analyzing the severity of clinical status and the outcome of patients with subarachnoid hemorrhage, we found that patients with poor clinical status, as measured by the Glasgow Coma Scale (GCS) and the Hunt and Hess scale, had significantly lower lymphocyte counts and higher NL-R, PL-R and SII values than those with good clinical status. Additionally, patients with lower GCS scores presented a lower proportion of CD3+CD4-CD8- cells. Worse outcomes assessed at discharge were associated with lower lymphocyte counts but higher PL-R values. CONCLUSIONS: The current study pointed to the significance of systemic immune and inflammatory responses after IA rupture and the potential clinical utility of hematological parameters, which can be easily calculated. In particular, the role of DN T cells and the significance of the SII as a marker related to clinical status should be further investigated.

Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms.

BACKGROUND: Rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. Our previous study revealed a downregulation of genes related to T lymphocytes and an upregulation of genes related to monocytes and neutrophils after IA rupture. It remains unknown whether that resulted from alterations in transcription or cell count. We sought to characterize the systemic response to IA rupture through analysis of transcript expression profiles in peripheral blood cells. We also investigated effects of IA rupture on the composition of mononuclear cells in peripheral blood. METHODS: We included 19 patients in the acute phase of IA rupture (RAA, first 72 h), 20 patients in the chronic phase (RAC, 3-15 months), and 20 controls. Using deep transcriptome sequencing, we analyzed the expression of protein-coding and noncoding RNAs. Expression levels, transcript biotypes, alternative splicing and other features of the regulated transcripts were studied. A functional analysis was performed to determine overrepresented ontological groups among gene expression profiles. Flow cytometry was used to analyze alterations in the level of mononuclear leukocyte subpopulations. RESULTS: Comparing RAA and controls, we identified 491 differentially expressed transcripts (303 were downregulated, and 188 were upregulated in RAA). The results indicate that the molecular changes in response to IA rupture occur at the level of individual transcripts. Functional analysis revealed that the most impacted biological processes are related to regulation of lymphocyte activation and toll-like receptor signaling pathway. Differences between RAC and controls were less prominent. Analysis of leukocyte subsets revealed a significantly decreased number of CD4+ lymphocytes and increase of classical and intermediate monocytes in RAA patients compared to controls. CONCLUSIONS: IA rupture in the acute phase strongly influences the transcription profiles of peripheral blood cells as well as the composition of mononuclear cells. A specific pattern of gene expression alteration was found, suggesting a depression of lymphocyte response and enhancement of monocyte activity.

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.

Predictors of Class I epilepsy surgery outcome in tumour-related chronic temporal lobe epilepsy in adults.

OBJECTIVE: Temporal lobe tumours, especially low-grade gliomas and glioneuronal tumours, are common causes of seizures in patients referred for epilepsy surgery. We here present our experience of surgical treatment of patients with intractable chronic epilepsy associated with temporal lobe tumours, focusing on the long-term surgical outcomes and the features associated with better seizure control. METHODS: In this study, we retrospectively analysed 44 consecutive patients from a total of 182 with refractory temporal lobe epilepsy presenting with long-term intractable epilepsy due to a temporal lobe tumour who were surgically treated at our institution between 2005 and 2015 with post-surgical follow-up of at least two years. All patients underwent a standard pre-surgical evaluation that included: history and physical examination with a description of the seizure semiology, serial scalp EEG recording, brain MR imaging, and a detailed neuropsychological evaluation. Our surgical strategy comprised tumour resection, and combined mesial temporal and neocortical resection in most cases. RESULTS: No patient died during surgery or the postoperative course. Seven patients had postoperative complications, of whom two had permanent hemiparesis due to ischaemic stroke. At the final follow-up, a favourable seizure outcome (Engel Class I) was found in 37 patients (84%), including 31 (70.5%) in Engel Class IA (excellent result). Two (4.5%) patients presented with an Engel Class II outcome (unfavourable outcome). Five patients (11.5%) were in Engel Classes III or IV (surgical failure). We found that complete resection of the hippocampus along with tumour and temporal pole removal was strongly associated with seizure freedom (p = 0.015). Pathological diagnosis was also a significant prognostic indicator of tumour-related seizure freedom. Patients with a diagnosis of a glioneuronal tumour benefited from more seizure freedom after resection compared to those who had a low-grade glioma (p = 0.024). CONCLUSION: The most appropriate management of tumour-related chronic temporal lobe epilepsy in adults appears to be tai-lored temporal lobe resection including tumour and hippocampal complex removal. Surgical treatment of tumoural temporal lobe epilepsy demonstrates excellent results in terms of seizure improvement, especially in patients with glioneuronal tumours.

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.