The Potential Role of RANTES in Post-Stroke Therapy.

One of the key response mechanisms to brain damage, that results in neurological symptoms, is the inflammatory response. It triggers processes that exacerbate neurological damage and create the right environment for the subsequent repair of damaged tissues. RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted) chemokine(C-C motif) ligand 5 (CCL5) is one of the chemokines that may have a dual role in stroke progression involving aggravating neuronal damage and playing an important role in angiogenesis and endothelial repair. This study concerned patients with ischemic stroke (AIS), whose CCL5 concentration was measured at various time intervals and was compared with the control group. In addition, the effect of this biomarker on neurological severity and functional prognosis was investigated. Compared to healthy patients, a higher concentration of this chemokine was demonstrated in less than 4.5 h, 24 h and on the seventh day. Differences in CCL5 levels were found to be dependent on the degree of disability and functional status assessed according to neurological scales (modified Rankin Scale, National Institutes of Health Stroke Scale). In addition, differences between various subtypes of stroke were demonstrated, and an increase in CCL5 concentration was proven to be a negative predictor of mortality in patients with AIS. The deleterious effect of CCL5 in the acute phase of stroke and the positive correlation between the tested biomarkers of inflammation were also confirmed.

Angiogenin Levels and Carotid Intima-Media Thickness in Patients with Type 1 Diabetes and Metabolic Syndrome.

It is well documented that in patients with type 1 diabetes (DM1), decreased levels of angiogenin are associated with the development of overt nephropathy. However, little is known about angiogenin levels and subclinical macrovascular organ damage in patients with DM1 and concomitant metabolic syndrome (MS). Therefore, we analyzed the relationship between angiogenin levels and carotid intima-media thickness (cIMT) in DM1 patients with and without MS. We found that angiogenin concentration was significantly lower in DM1 patients compared to controls, while the cIMT measurements were comparable. Exclusion of patients with MS, patients with hypertension, undergoing treatment, or cigarette smokers did not change these findings. Of note, when comparing the subgroups of DM1 patients with and without MS, there was no significant difference between angiogenin levels. However, we did note a significant difference in these levels after the exclusion of smokers. The comparison of cIMT in these subgroups showed a significant difference between the study subgroups. This difference was no longer observed when the age of the patients was taken into account. In summary, it can be concluded that metabolic syndrome in patients with type 1 diabetes does not appear to impact angiogenin levels or cIMT.

Polish recommendations for diagnosis and therapy of paediatric stroke.

Stroke remains one of the greatest health challenges worldwide, due to a high mortality rate and, despite great progress in its treatment, the significant disability that it causes. Studies conducted around the world show that the diagnosis of stroke in children is often significantly delayed. Paediatric ischaemic arterial stroke (PAIS) is not only a problem that varies greatly in frequency compared to the adult population, it is also completely different in terms of its risk factors, clinical course and outcome. The main reason for the lack of a rapid diagnosis of PAIS is a lack of access to neuroimaging under general anaesthesia. The insufficient knowledge regarding PAIS in society as a whole is also of great importance. Parents and carers of children should always bear in mind that paediatric age is not a factor that excludes a diagnosis of stroke. The aim of this article was to develop recommendations for the management of children with acute neurological symptoms suspected of ischaemic stroke and further treatment after confirmation of the ischaemic aetiology of the problem. These recommendations are based on current global recommendations for the management of children with stroke, but our goal was also to match them as closely as possible to the needs and technical diagnostic and therapeutic possibilities encountered in Poland. Due to the multifactorial problem of stroke in children, not only paediatric neurologists but also a neurologist, a paediatric cardiologist, a paediatric haematologist and a radiologist took part in the preparation of these recommendations.

Assessment of Low-Level Air Pollution and Cardiovascular Incidence in Gdansk, Poland: Time-Series Cross-Sectional Analysis.

(1) Background: More than 1.8 million people in the European Union die every year as a result of CVD, accounting for 36% of all deaths with a large proportion being premature (before the age of 65). There are more than 300 different risk factors of CVD, known and air pollution is one of them. The aim of this study was to investigate whether daily cardiovascular mortality was associated with air pollutants and meteorological conditions in an urban environment with a low level of air pollution. (2) Methods: Data on daily incidence of strokes and myocardial infarctions in the city of Gdansk were obtained from the National Health Fund (NHF) and covered the period from 1 January 2014 to 31 December 2018. Data on the level of pollution, i.e., SO2, NO, NO2, NOx, CO, PM10, PM2.5, CO2, O3 and meteorological conditions came from the foundation: Agency of Regional Air Quality Monitoring in the Gdansk metropolitan area (ARMAG). Using these data, we calculated mean values with standard deviation (SD) and derived the minimum and maximum values and interquartile range (IQR). Time series regression with Poisson distribution was used in statistical analysis. (4) Results: Stroke incidence is significantly affected by an increase in concentrations of NO, NO2 and NOx with RRs equal to 1.019 (95%CI: 1.001-1.036), 1.036 (95%CI: 1.008-1.064) and 1.017 (95%CI: 1.000-1.034) for every increase in IQR by 14.12, 14.62 and 22.62 µg/m3, respectively. Similarly, myocardial infarction incidence is significantly affected by an increase in concentrations of NO, NO2 and NOx with RRs equal to 1.030 (95%CI: 1.011-1.048), 1.053 (95%CI: 1.024-1.082) and 1.027 (95%CI: 1.010-1.045) for every increase in IQR by 14.12, 14.62 and 22.62 µg/m3, respectively. Both PM10 and PM2.5 were positively associated with myocardial infarction incidence. (5) Conclusions: In this time-series cross-sectional study, we found strong evidence that support the hypothesis that transient elevations in ambient PM2.5, PM10, NO2, SO2 and CO are associated with higher relative risk of ischemic stroke and myocardial infarction incidents.

Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics.

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients' outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.

Selected Mediators of Inflammation in Patients with Acute Ischemic Stroke.

During a stroke, a series of biochemical and metabolic changes occur which eventually lead to the death of cells by necrosis or apoptosis. This is a multi-stage process involving oxidative stress and an inflammatory response from the first signs of occlusion of a blood vessel until the late stages of regeneration and healing of ischemic tissues. The purpose of the research was to assess the concentration of pro-inflammatory cytokines IL-6 and TNF-α in the blood serum of patients with ischemic stroke (AIS) and to investigate their role as new markers in predicting functional prognosis after thrombolytic therapy. The researches have shown that the concentrations of the measured biomarkers were higher compared to the control group. Serum levels of IL-6 and THF-α before the initiation of intravenous thrombolysis were lower in the subgroup of patients with a favourable functional result (mRS: 0−2 pts) compared to the group of patients with an unfavourable functional result (mRS: 3−6 pts). A positive correlation was found between the concentration of IL-6 and TNF-α in patients with AIS during <4.5 h and on one day after the onset of stroke, which means that the concentration of IL-6 increases with the increase in TNF-α concentration. It has also been shown that higher levels of IL-6 in the acute phase of stroke and on the first and seventh days, and TNF-α during onset, were associated with poorer early and late prognosis in patients treated with intravenous thrombolysis. A relationship was found between the level of IL-6 and TNF-α in the subacute AIS and the severity of the neurological deficit. It has been shown that the investigated biomarkers may be a prognostic factor in the treatment of thrombolytic AIS.

Cognitive Functions Associated with Brain Imaging Markers in Patients with Psoriasis.

Psoriasis is a severe inflammatory disease associated with a higher comorbidity of depression, cognitive dysfunction and brain atrophy. The association between psoriasis, magnetic resonance imaging (MRI) markers and cognitive impairment has rarely been investigated, and the existing results are conflicting. METHODS: This study included 89 subjects (53 patients with psoriasis and 36 healthy controls). The severity of psoriasis was evaluated using the Psoriasis Area and Severity Index (PASI) score; for depression, the Hospital Anxiety and Depression Scale (HADS) scale was used. Neuropsychological tests were also applied, including a Trail Making Test (TMT) as well as Digit Span, Stroop, Verbal Fluency and Rey Auditory Verbal Learning tests. MRI scans were performed using a 1.5 T scanner. Brain volumetry, white matter lesions, grey matter and white matter were evaluated. The extent of these changes was assessed on the Fazekas scale. The differences between groups were evaluated using a Student's t-test and a Mann-Whitney U test, and a Pearson correlation analysis was also performed. RESULTS: Patients with psoriasis presented worse achievements on all the neuropsychological tests and showed more intense changes on MRI compared to healthy controls. The severity of psoriasis as determined by PASI scores was associated with depression, and a greater psychomotor slowness severity of changes in the brain was associated with poorer results on the neurological tests. CONCLUSIONS: Our results indicate the possibility of progressive brain atrophy related to cognitive decline in psoriasis.

Systemic thrombolysis in ischaemic stroke patients with COVID-19.

OBJECTIVE: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is the core medical therapy of acute ischaemic stroke (AIS). COVID-19 infection negatively modifies acute stroke procedures and, due to its pro-coagulative effect, may potentially impact on IVT outcome. Thus, short-term efficacy and safety of IVT were compared in patients with and without evidence of SARS-CoV-2. METHODS: An observational, retrospective study included 70 patients with AIS, including 22 subjects (31%) with evidence of acute COVID-19 infection, consecutively treated with IVT in 4 stroke centres between 15 September and 30 November 2020. RESULTS: Patients infected with COVID-19 were characterized by higher median of National Institute of Health Stroke Scale (NIHSS) score (11.0 vs. 6.5; p < .01) and D-dimers (870 vs. 570; p = .03) on admission, higher presence of pneumonia (47.8% vs. 12%; p < .01) and lower percentage of 'minor stroke symptoms' (NIHSS 1-5 pts.) (2% vs., 18%; p < .01). Hospitalizations were longer in patients with COVID-19 than in those without it (17 vs. 9 days, p < .01), but impact of COVID-19 infection on patients' in-hospital mortality or functional status on dismission has been confirmed neither in uni- or multivariate analysis. CONCLUSION: SARS-CoV-2 infection prolongs length of stay in hospital after IVT, but does not influence in-hospital outcome.

Skin oxygenation impairment is associated with increased total cholesterol level in children with short-lasting type 1 diabetes mellitus.

INTRODUCTION: Transcutaneous oxygen pressure (tcPO2) is a non-invasive method of measuring skin oxygenation that may reflect its superficial perfusion. Skin microvasculature may be impaired in patients with late onset of type 1 diabetes (DM1). However, its condition in children has not been fully determined. AIM: To compare tcPO2 in children with short-lasting non-complicated DM1 and age-matched healthy controls with regard to concomitant vascular risk factors. MATERIAL AND METHODS: The study group consisted of 51 paediatric patients aged 14.9 (8.4-18.0) years with short-lasting DM1 without clinical evidence of diabetic micro- or macroangiopathy and 28 control subjects aged 14.8 (11.3-17.7) years. TcPO2 was tested prior, during and after applying post-occlusive reactive hyperaemia (PORH) test in standardized conditions. Biochemical parameters were assessed and then compared between the groups. RESULTS: TcPO2 at maximal ischemia during PORH was higher in the DM1 patients than in healthy controls (2.4 (0.7-18.8) vs. 1.6 (0.4-12.0), p = 0.002). No differences were found regarding the tcPO2 measurements recorded prior to ischemia or after recovery. In DM1, concentrations of total cholesterol, triglycerides, HbA1c and TSH were significantly higher than in healthy controls. The fT4 levels were significantly lower in the DM1 group. After adjusting for lipid levels, no differences in tcPO2 were found, and a multivariate analysis showed the cholesterol levels have a significant impact on tcPO2 response to maximal ischemia. CONCLUSIONS: Our results indicate that increased lipid levels are responsible for the impaired skin response to ischemic stimuli in short-lasting DM1. This supports the importance of aggressive lipid control in prevention of early onset microangiopathy in those patients.

Stroke Care During the First and the Second Waves of the COVID-19 Pandemic in a Community Hospital.

Objective: The coronavirus disease 2019 (COVID-19) infection may alter a stroke course; thus, we compared stroke course during subsequent pandemic waves in a stroke unit (SU) from a hospital located in a rural area. Methods: A retrospective study included all patients consecutively admitted to the SU between March 15 and May 31, 2020 ("first wave"), and between September 15 and November 30, 2020 ("second wave"). We compared demographic and clinical data, treatments, and outcomes of patients between the first and the second waves of the pandemic and between subjects with and without COVID-19. Results: During the "first wave," 1.4% of 71 patients were hospitalized due to stroke/TIA, and 41.8% of 91 during the "second wave" were infected with SARS-CoV-2 (p < 0.001). During the "second wave," more SU staff members were infected with COVID-19 than during the "first wave" (45.6 vs. 8.7%, p < 0.001). Nevertheless, more patients underwent intravenous thrombolysis (26.4 vs. 9.9%, p < 0.008) and endovascular thrombectomy (5.3 vs. 0.0%, p < 0.001) during the second than the first wave. Large vessel occlusion (LVO) (OR 8.74; 95% CI 1.60-47.82; p = 0.012) and higher 30-day mortality (OR 6.01; 95% CI 1.04-34.78; p = 0.045) were associated with patients infected with COVID-19. No differences regarding proportions between ischemic and hemorrhagic strokes and TIAs between both waves or subgroups with and without COVID-19 existed. Conclusion: Despite the greater COVID-19 infection rate among both SU patients and staff during the "second wave" of the pandemic, a higher percentage of reperfusion procedures has been performed then. COVID-19 infection was associated with a higher rate of the LVO and 30-day mortality.

Cerebral microbleeds in neurological practice: concepts, diagnostics and clinical aspects.

INTRODUCTION: Due to the widespread use of magnetic resonance imaging (MRI) in neurological diagnostics, the number of patients detected as having cerebral microbleeds (CMBs) continues to increase. However, their clinical impact still remains controversial, especially the question of whether CMBs significantly increase the risk of life-threatening intracerebral haemorrhage (ICH) in patients undergoing intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT), or in patients on anticoagulant therapy or statins. STATE OF THE ART: The term 'CMB' is a radiological concept that aims to illustrate microscopic pathology of perivascular hemosiderin deposits corresponding most probably to small foci of past bleeding. MRI images in sequence T2*-GRE and susceptibility-weighted imaging (SWI) are used for a diagnosis of a CMB. This review summarises the current knowledge regarding the definition, prevalence, genetics, risk factors, radiological diagnosis and differential diagnosis of a CMB. We discuss its role as an indicator of future ischaemic or haemorrhagic events in high risk patients or those on antiplatelet or anticoagulant therapy, and its prognostic value for reperfusion strategies and for the development of dementia. FUTURE DIRECTION: The place of CMBs in current guidelines is explored herein. It must be emphasised that the recommendations relating to CMBs are expert opinions. Therefore, at the end of this review, we pose a number of questions that future clinical trials should answer.

COVID-19 - neuropathological point of view, pathobiology, and dilemmas after the first year of the pandemic struggle.

This article constitutes a summary of the knowledge on the involvement of the nervous system in COVID-19, concerning its general pathobiology, clinical presentation and neuropathological features as well as the future directions of investigation. Variable definitions, selection bias, mainly retrospective analyses of hospitalized patients and different methodologies are implemented in the research of this new disease. Central nervous system (CNS) pathology presents most frequently features of non-specific neuroinflammation with microglial activation and lymphoid infiltrations, ischemic/hypoxic encephalopathy, acute cerebrovascular disease, and microthrombi. Some brain specimens remain unaffected or show only non-specific changes of the critical status. Interpretations of the neuropathological findings are not always balanced in a clinical context and discrepant in consequence. Designing of longitudinal neuropathological studies, more frequent autopsies, and building of COVID-19 brain banks, together with neuroimaging analyses is essential. Genetic predispositions or immunological factors corresponding to the disease profile as well as cerebrospinal fluid (CSF) or serum biomarkers of COVID-19, the impact of different virus variants and influence of the therapy need to be identified. The mechanisms causing neuroCOVID and cognitive impairment - whether they are infectious, toxic, vascular or metabolic - create other aspects under research. There are also many existential questions about post-COVID and delayed sequelae of the infection. The fight with pandemic is a challenge for the global society, with neuropathologists and neuroscientists as important allies in struggle for understanding and conquering COVID-19.

Cerebral Thrombolysis in Rural Residents Aged ≥ 80.

PURPOSE: The proportion of older people in Poland is higher in rural areas than in urban areas. Thus, we aimed to evaluate treatment rate and factors associated with outcome and safety of intravenous thrombolysis (IVT) in rural residents aged ≥80 years admitted to primary stroke centers. PATIENTS AND METHODS: This study was a retrospective, observational cohort study of 873 patients treated with recombinant tissue plasminogen activator (rt-PA) in primary stroke centers between February 1, 2009 and December 31, 2017. Among them were 527 rural residents and 231 (26.5%) were ≥80 years of age. The analyses between rural and urban patients aged ≥80 and between rural patients aged <80 and aged ≥80 were performed. RESULTS: The proportion of patients aged ≥80 treated with rt-PA was comparable in rural and urban residents (27.9% vs 24.3% p = 0.24). Rural patients aged ≥80 were also characterized by lower incidence of cardiovascular risk factors and better patients' conditions on admission to hospital. Symptomatic intracerebral hemorrhage rate among ≥80-year-old stroke patients was lower in those living in rural areas than in those living in urban areas (5.4% vs 14.3%, p = 0.02); there were no differences regarding mortality and 3-month functional outcome between both populations. The older group of rural patients was characterized by a higher 3-month mortality (28.5% vs 12.6%, p < 0.001) and lower functional independence rate (34.0% vs 50.5%, p < 0.001) than rural younger patients. Antiplatelet (OR 2.43, 95% CI 1.04-5.66, p = 0.04) and anticoagulant therapy before stroke (OR 3.64, 95% CI 1.21-10.99, p = 0.022), early ischemic changes in baseline computerized tomograprpahy (OR 2.65, 95% CI 1.03-6.82, p = 0.043) were associated with unfavorable outcome; and higher National Institute of Health Stroke Scale score on admission (OR 1.01, 95% CI 1.01-1.20, p = 0.039), higher baseline count of white blood cells (OR 1.33, 95% CI 1.10-0.62, p = 0.003) were associated with mortality in rural patients over 80. CONCLUSION: We suggest that rural patients aged ≥80 may be safely treated with IVT in routine practice. However, lower efficacy and a higher mortality must be considered in former use of Vitamin K antagonist and antiplatelet or high white blood cells count.

Effect of IL-6 and hsCRP Serum Levels on Functional Prognosis in Stroke Patients Undergoing IV-Thrombolysis: Retrospective Analysis.

PURPOSE: We evaluated the relationship between pretreatment IL-6 and hsCRP levels, symptom severity and functional outcome of patients with acute ischemic stroke (AIS) treated with IV-thrombolysis. PATIENTS AND METHODS: IL-6 and hsCRP samples were obtained from 83 consecutively treated Caucasian patients with AIS prior to initiation of IV-thrombolysis. Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS), whereas functional outcome was assessed with modified Rankin Scale (mRS). The commercially available sets of enzymatic immune tests were used to estimate the concentrations of inflammatory markers in serum. RESULTS: Medians of IL-6 serum concentrations prior to IV-thrombolysis were lower in patients with favorable (mRS 0-2 pts) functional outcome than in those with unfavorable (mRS 3-6 pts) functional outcome, both at hospital dismission (5.92: 2.30-7.71 vs 9.46: 3.79-17.29 pg/mL; p<0.01) and on the ninetieth day from stroke onset (5.87: 2.30-10.58 vs 10.9: 5.94-17.28 pg/mL; p<0.01). There were no existing differences regarding hsCRP levels between groups (2.49: 0.11-9.82 vs 4.44: 0.32-9.87 mg/dL; p=0.30 and 2.57: 0.11-2.57 vs 2.83: 0.32-9.32 mg/dL; p=0.75, respectively). Patients with lacunar strokes were characterized by lower median of IL-6 (5.96: 2.87-13.0% vs 7.29: 2.30-17.28; p=<0.02) and hsCRP (2.25: 0.11-9.82 vs 4.84: 0.35-9.87; p=0.01) than those with nonlacunar infarctions. Multivariate analysis showed an impact of IL-6 on mRS measured on hospital dismission and after three months, regardless of their initial NIHSS, presence of hemorrhagic transformation and type 2 diabetes. No impact of hsCRP, lacunar etiology and patients' age on functional outcome existed. CONCLUSION: Regardless of the stroke etiology, pretreatment of IL-6, but not of hsCRP levels, may help to predict functional outcome after IV-thrombolysis independently of symptom severity and stroke complications.

Common carotid pulsatility is deteriorated by autoimmune thyroiditis in children with type 1 diabetes mellitus - A pilot study.

Autoimmune thyroiditis (AIT) frequently coexists with type 1 diabetes (DM1) and additionally increases the extent of microcirculatory complications due to DM1. We hypothesized that in pediatric patients with DM1, impairment of macrocirculation could be further augmented by a coexisting autoimmune process. Therefore, we investigated the influence of AIT on large arteries in DM1 pediatric patients. Our group consisted of 19 DM1, 19 DM1 + AIT patients and 29 control subjects. The groups were comparable regarding age and gender. The DM1 and DM1 + AIT patients were matched for age at onset of DM1 and diabetes duration. Macrocirculation was described using pulsatility indices (PIs) determined for common carotid (CCA) and peripheral arteries of upper and lower limbs. CCA resistance index (RI) and ABI were also assessed. Children with DM1 + AIT had only significantly lower CCA_PI and CCA_RI in comparison with controls whereas in the absence of AIT such difference was not found. The diabetes duration and age of onset did not correlate with carotid indices. Total cholesterol level was higher both in DM1 + AIT and DM1 groups than in the control group. For low density lipoproteins cholesterol, a significant difference was found between DM1 + AIT and control groups. Age-independent impact of AIT on CCA_PI was confirmed by multivariate analysis. Common carotid pulsatility is deteriorated by autoimmune thyroiditis independently of age in children with type 1 diabetes mellitus.

Endothelial Progenitor Cells as a Marker of Vascular Damage But not a Predictor in Acute Microangiopathy-Associated Stroke.

BACKGROUND: The aim of the study was to assess the number of endothelial progenitor cells (EPCs) in patients with acute stroke due to cerebral microangiopathy and evaluate whether there is a relationship between their number and clinical status, radiological findings, risk factors, selected biochemical parameters, and prognosis, both in ischemic and hemorrhagic stroke. METHODS: In total, 66 patients with lacunar ischemic stroke, 38 patients with typical location hemorrhagic stroke, and 22 subjects from the control group without acute cerebrovascular incidents were included in the prospective observational study. The number of EPCs was determined in serum on the first and eighth day after stroke onset using flow cytometry and identified with the immune-phenotype classification determinant (CD)45-, CD34+, CD133+. RESULTS: We demonstrated a significantly higher number of EPCs on the first day of stroke compared to the control group (med. 17.75 cells/µL (0-488 cells/µL) vs. 5.24 cells/µL (0-95 cells/µL); p = 0.0006). We did not find a relationship between the number of EPCs in the acute phase of stroke and the biochemical parameters, vascular risk factors, or clinical condition. In females, the higher number of EPCs on the first day of stroke is related to a favorable functional outcome on the eighth day after the stroke onset compared to males (p = 0.0355). We found that a higher volume of the hemorrhagic focus on the first day was correlated with a lower number of EPCs on the first day (correlation coefficient (R) = -0.3378, p = 0.0471), and a higher number of EPCs on the first day of the hemorrhagic stroke was correlated with a lower degree of regression of the hemorrhagic focus (R = -0.3896, p = 0.0367). CONCLUSION: The study showed that endothelial progenitor cells are an early marker in acute microangiopathy-associated stroke regardless of etiology and may affect the radiological findings in hemorrhagic stroke. Nevertheless, their prognostic value remains doubtful in stroke patients.

The Role of Selected Pro-Inflammatory Cytokines in Pathogenesis of Ischemic Stroke.

Stroke is currently one of the most common causes of death and disability in the world, and its pathophysiology is a complex process, involving the oxidative stress and inflammatory reaction. Unfortunately, no biochemical factors useful in the diagnostics and treatment of stroke have been clearly established to date. Therefore, researchers are increasingly interested in the inflammatory response triggered by cerebral ischemia and its role in the development of cerebral infarction. This article gives an overview of the available literature data concerning the role of pro-inflammatory cytokines in acute stroke. Detailed analysis of their role in cerebral circulation disturbances can also suggest certain immune response regulatory mechanisms aimed to reduce damage to the nervous tissue in the course of stroke.

The Prognostic Value of High Platelet Reactivity in Ischemic Stroke Depends on the Etiology: A Pilot Study.

BACKGROUND: Reduced aspirin response may result in a worse prognosis and a poor clinical outcome in ischemic stroke. The aim of this prospective pilot study was to assess the relationship between platelet reactivity and early and late prognosis, and the clinical and functional status in ischemic stroke, with the role of stroke etiology. METHODS: The study involved 69 subjects with ischemic stroke, divided into large and small vessel etiological subgroups. Platelet function testing was performed with two aggregometric methods-impedance and optical-while the clinical condition was assessed using the National Institute of Health Stroke Scale (NIHSS) and the functional status was assessed using the modified Rankin Scale (mRS) on the first and eighth day (early prognosis) and the 90th day of stroke (late prognosis). RESULTS: The initial platelet reactivity was found to be higher in patients with severe neurological deficits on the 90th day after stroke, than in the group with mild neurological deficits (median, respectively, 40 area under the curve (AUC) units vs. 25 AUC units, p = 0.033). In the large vessel disease group, a significant correlation between the platelet reactivity and the functional status on the first day of stroke was found (correlation coefficient (R) = 0.4526; p = 0.0451), the platelet reactivity was higher in the subgroup with a severe clinical condition compared to a mild clinical condition on the first day of stroke (p = 0.0372), and patients resistant to acetylsalicylic acid (aspirin) had a significantly greater possibility of a severe neurological deficit on the first day of stroke compared to those who were sensitive to aspirin (odds ratio (OR) = 14.00, 95% confidence interval (CI) 1.25-156.12, p = 0.0322). CONCLUSION: High on-treatment platelet reactivity in ischemic stroke was associated with a worse late prognosis regardless of the etiology. We demonstrated a significant relationship between high platelet reactivity and worse early prognosis and poor clinical and functional condition in the large vessel etiologic subgroup. However, due to the pilot nature of this study, its results should be interpreted with caution and further validation on a larger cohort is required.

Aspirin Resistance Affects Medium-Term Recurrent Vascular Events after Cerebrovascular Incidents: A Three-Year Follow-up Study.

Background: The aim of this prospective, a three-year follow-up study, was to establish the role of high on-treatment platelet reactivity (HTPR) in predicting the recurrence of vascular events in patients after cerebrovascular incidents, particularly in the aspect of stroke etiology. Methods: The study included 101 subjects with non-embolic cerebral ischemia (69 patients with ischemic stroke and 32 patients with transient ischemic attack) treated with 150 mg of acetylsalicylic acid (aspirin) a day. The platelet reactivity was tested in the first 24 h after the onset of cerebral ischemia by impedance aggregometry. Recurrent vascular events, including recurrent ischemic stroke, transient ischemic attack, myocardial infarction, systemic embolism, or sudden death of vascular reason, were assessed 36 months after the onset of cerebral ischemia. Results: Recurrent vascular events occurred between 3 and 9 months after onset in 8.5% of all subjects; in the HTPR subgroup, recurrent vascular events occurred in 17.9%; in the normal on-treatment platelet reactivity (NTPR) subgroup, they occurred in 4.6%. We did not notice early or long-term recurrent events. Aspirin resistant subjects had a significantly higher risk of recurrent vascular events than did aspirin sensitive subjects (Odds ratio (OR) = 4.57, 95% Confidence interval (CI) 1.00-20.64; p = 0.0486). Cox proportional hazard models showed that large-vessel disease (Hazard ratio (HR) 12.04, 95% CI 2.43-59.72; p = 0.0023) and high on-treatment platelet reactivity (HR 4.28, 95% CI 1.02-17.93; p = 0.0465) were independent predictors of recurrent vascular events. Conclusion: Aspirin resistance in the acute phase of cerebral ischemia was associated with a higher risk of recurrent medium-term vascular events, coexisting with large-vessel etiology of stroke. Platelet function-guided personalized antiplatelet treatment should be considered for patients with recurrent strokes, especially when due to large-vessel disease.

High On-Treatment Platelet Reactivity Affects the Extent of Ischemic Lesions in Stroke Patients Due to Large-Vessel Disease.

BACKGROUND: Excessive platelet activation and aggregation plays an important role in the pathogenesis of ischemic stroke. Correlation between platelet reactivity and ischemic lesions in the brain shows contradictory results and there are not enough data about the potential role of stroke etiology and its relationships with chronic lesions. The aim of this study is to assess the relationship between platelet reactivity and the extent of ischemic lesions with the particular role of etiopathogenesis. METHODS: The study involved 69 patients with ischemic stroke, including 20 patients with large-vessel disease and 49 patients with small-vessel disease. Evaluation of platelet reactivity was performed within 24 h after the onset of stroke using two aggregometric methods (impedance and optical), while ischemic volume measurement in the brain was performed using magnetic resonance imaging (in diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences) at day 2-5 after the onset of stroke. RESULTS: In the large-vessel disease subgroup, a correlation was found between platelet reactivity and acute ischemic focus volume (correlation coefficient (R) = 0.6858 and p = 0.0068 for DWI; R = 0.6064 and p = 0.0215 for FLAIR). Aspirin-resistant subjects were significantly more likely to have a large ischemic focus (Odds Ratio (OR) = 45.00, 95% Confidence Interval (CI) = 1.49-135.36, p = 0.0285 for DWI; OR = 28.00, 95% CI = 1.35-58.59, p = 0.0312 for FLAIR) than aspirin-sensitive subjects with large-vessel disease. CONCLUSION: In patients with ischemic stroke due to large-vessel disease, high on-treatment platelet reactivity affects the extent of acute and chronic ischemic lesions.