Circulating Chemokines and Short- and Long-Term Outcomes After Ischemic Stroke.

Chemokines are vital in post-cerebral ischemia inflammatory reactions. We investigate the possible relationship between plasma chemokines and short-term and long-term outcomes after stroke. This study included 235 patients (median age, 72 years; 49.8% female) suffering from ischemic stroke, or transient ischemic attack admitted to the hospital within 24 h of onset. We evaluated chemokines CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in plasma samples collected upon admission. Further, we assessed functional outcomes at 3- and 12-months, all-cause fatality over 5 years, and episodes of delirium within the first 7 days of admission. Multivariate analysis revealed an association between higher CXCL10 levels and an increased risk of poor functional outcomes at 3 months (OR: 3.02, 95%CI: 1.22-7.46, p = 0.016) and 12 months (OR: 2.32, 95%CI: 1.03-5.26, p = 0.043), as well as an increased death risk (HR: 1.79, 95%CI: 1.04-3.07, p = 0.036). High CXCL8 levels independently predicted poor functional outcomes at 12 months (OR: 2.69, 95%CI: 1.39-6.31, p = 0.005) and a higher 5-year case fatality rate (HR: 1.90, 95%CI: 1.23-2.93, p = 0.004). Elevated CXCL9 levels also predicted unfavourable functional outcomes at 12 months (OR: 2.45, 95%CI: 1.07-5.61, p = 0.034). In univariate analysis, increased levels of CXCL8, CXCL9, and CXCL10 showed an association with delirium, although this link was not evident in the multivariate analysis. Plasma CXCL8 and CXCL10 show potential as prognostic biomarkers for stroke outcomes and as therapeutic targets suitable for reverse translation.

Risk factors of acute kidney injury during hospitalization in acute ischaemic stroke patients undergoing mechanical thrombectomy.

Introduction: Acute kidney injury (AKI) seems to worsen the prognosis of acute ischaemic stroke (AIS) patients treated with mechanical thrombectomy (MT). At the same time, the procedure of MT increases AKI risk by iodinated contrast use. Identification of factors predisposing to AKI after MT is important for recognizing vulnerable patients and successful prevention. Aim: To identify factors associated with the occurrence of AKI during hospitalization in MT-treated AIS patients. Material and methods: The study included all AIS patients treated with MT in the University Hospital in Krakow from 2019 to 2021. The diagnosis of AKI during hospitalisation was based on serum creatinine concentration levels, according to the Kidney Disease Improving Global Outcomes guidelines. We compared patients with and without AKI in terms of age, sex, comorbidities, stroke course and laboratory test results at admission. We identified factors associated with the occurrence of AKI using univariate logistic regression analysis, with significant variables subsequently added to the multivariate analyses. Results: Among 593 MT-treated AIS patients the incidence of AKI during hospitalisation was 12.6%. AKI development was associated with diabetes, chronic kidney disease, total volume of iodinated contrast obtained during hospitalisation, posterior circulation stroke, lack of intravenous thrombolysis, and laboratory test results at admission: haemoglobin, glucose, urea, potassium, and creatinine. Total contrast volume and urea level were the most important independent risk factors associated with occurrence of AKI. Conclusions: AKI is common in MT-treated AIS patients. There is a need to establish a protocol for decreasing the risk of AKI in AIS patients undergoing MT and, in case it occurs, a procedure for its treatment.

Association of Imaging-based Predictors with Outcome in Different Treatment Options for Intracerebral Hemorrhage.

PURPOSE: Intracerebral hemorrhage is the deadliest form of stroke. This study aimed to enhance the prediction of 30-day mortality in intracerebral hemorrhage patients by integrating computational parameters. METHODS: This study retrospectively analyzed 435 patients with spontaneous intracerebral hemorrhage (ICH). Utilizing the acquired computed tomography (CT) images, we extracted the contour and visual representation of ICH. For the extracted contour, the analysis encompassed factors including compactness, fractal dimension, Fourier factor, and circle factor. For the images depicting ICH, we calculated various factors related to density distribution including mean, coefficient of variance, skewness and kurtosis, as well as texture parameters, such as energy, entropy, contrast and homogeneity. To assess the impact of surgical treatment on 30-day mortality, logistic regression analysis was used. RESULTS: A total of 126 patients (29.09%) died within 30 days. A total of 62 (14.25%) patients underwent surgical treatment. Multivariate logistic regression analysis revealed that surgical treatment was independently associated with a lower risk of 30-day mortality (odds ratio, OR 0.226, 95% confidence interval, CI 0.049-0.85; p = 0.039). Based on the moderated analysis, we found that the volume of ICH (OR 0.905, 95% CI 0.902-0.908; p < 0.001) and ICH energy (OR 1.389, 95%CI 0.884-0.988; p = 0.010) had positive moderating effect on such associations while the presence of intraventricular blood had negative moderating effect (OR 1.154, 95% CI 1.034-1.628; p = 0.010). CONCLUSION: Patients exhibiting a higher volume and energy of ICH might benefit from surgical treatment; however, this efficacy was found to be diminished in cases involving the presence of intraventricular blood.

Sex Alters the Effect of Perfusion Deficits on Functional Outcome in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

INTRODUCTION: The discourse surrounding differences in cerebral hemodynamics and clinical outcomes among male and female patients treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains unresolved. We aimed to elucidate these differences by employing computed tomography perfusion (CTP) imaging before MT and examining the influence of perfusion deficits on the 90-day functional outcome. METHODS: This single-center retrospective analysis involved patients with anterior circulation AIS treated with MT at the Comprehensive Stroke Center, University Hospital, Krakow, from January 2019 to July 2023. We compared male and female patients in terms of baseline characteristics, CTP deficits, hypoperfusion intensity ratio (HIR, defined as T10max/T6max), and complications. The endpoints included the 90-day excellent functional outcome, defined as modified Rankin Score <2, and the 90-day mortality rate. RESULTS: We included 794 patients, of whom 408 were female (51.4%). Female patients had a smaller early infarct volume (median [interquartile range]: 7 mL [0-24.8] vs. 10 mL [0-33], p = 0.004), smaller penumbra volume (77.5 mL [46-117] vs. 99.5 mL [59.8-140], p < 0.001), lower HIR (0.34 [0.16-0.5] vs. 0.37 [0.2-9.53], p = 0.043) and were less likely to achieve an excellent functional outcome (55.6% vs. 66.1%, p = 0.003). For every 10 mL increase in early infarct volume, the odds for achieving an excellent outcome were lower in females (odds ratio [OR]: 0.82 [95% confidence interval: 0.73-0.92]) compared to males (OR: 0.96 [0.88-1.04]), whereas the risk of death was higher for females (OR: 1.25 [1.13-1.39] than for males (OR: 1.05 [0.98-1.14]). DISCUSSION: Despite more favorable cerebral hemodynamic profile, female AIS patients have worse outcomes than their male counterparts. This effect seems to be independently mediated by the more pronounced impact of early infarct volume on the prognosis in female patients. These findings underscore the possible explanatory power arising from sex-specific interpretation of early infarct volume in clinical practice.

Long-term outcomes of mechanical thrombectomy in acute ischaemic stroke patients with concomitant malignancy.

Introduction: Patients with cancer (CP) need a different approach to acute ischaemic stroke (AIS) treatment as intravenous thrombolysis (IVT) may be contraindicated. Mechanical thrombectomy (MT) is a treatment of choice for otherwise eligible patients, although the literature on its long-term outcomes in CP is limited. Aim: Assessing outcomes of MT-treated AIS patients with concomitant malignancy in a year-long follow-up. Material and methods: The study included 593 MT-treated AIS patients admitted in 2019-2021. The group was divided into CP (defined as a diagnosis of malignancy and undergoing/qualified for cancer treatment within previous 5 years) and a control group. The profile of cardiovascular risk factors, stroke severity and discharge, 90-day and 365-day outcomes were compared between the groups. Results: CP and controls had a similar profile of cardiovascular risk factors and comparable stroke severity. CP were less frequently treated with IVT (25.7% vs. 59.1%, p < 0.001). There were no differences between the groups in the successful reperfusion rate and occurrence of haemorrhagic complications. Discharge and 90-day outcomes were similar. CP had higher 365-day mortality (48.6% vs. 29.9%, p = 0.024) but the percentage of patients achieving good functional outcome in a year-long observation was comparable. Conclusions: Treatment with MT seems beneficial for AIS patients with concomitant malignancy both in short- and long-term observation.

Association between brain fog, cardiac injury, and quality of life at work after hospitalization due to COVID-19.

BACKGROUND: To evaluate incidence and search for possible predictors of brain fog and quality of life at work (QoL-W) among low-to-moderate risk subjects previously hospitalized due to COVID-19. MATERIAL AND METHODS: Participants aged ≥18 retrospectively reported 8 brain fog symptoms pre-COVID-19, at 0-4, 4-12 and >12 weeks post-infection via validated clinical questionnaire. The QoL-W was assessed with a 4-point Likert scale where 0, 1, 2, and 3 meant no, mild, moderate, and severe impairment in performing activities at work, respectively. Data on age, sex, comorbidities, and laboratory results (including first in-hospital high-sensitivity cardiac troponin I [hs-cTnI] measurement) were gathered. RESULTS: The study included 181 hospitalized subjects (age Me = 57 years), 37.02% women. Most had low disease severity (Modified Early Warning Score = 1, 77.90%) and low comorbidity (Charlson Comorbidity Index 0: 28.72%, 1-2: 34.09%), with no intensive care unit treatment needed. COVID-19 led to almost 3-fold increased brain fog symptoms, with incidence of 58.56%, 53.59%, and 49.17% within 4, 4-12, and >12 weeks, respectively (p < 0.001). First in-hospital hs-cTnI levels were 47.3% higher in participants who later presented with brain fog at median follow-up of 26.7 weeks since the diagnosis of the SARS-CoV-2 infection. Individuals who experienced at least one brain fog symptom at follow-up, had elevated hs-cTnI, less often presented with atrial fibrillation, and used anticoagulants during initial hospitalization due to COVID-19. The Hs-cTnI >11.90 ng/l predicted brain fog symptoms in multivariable model. COVID-19 was associated with 3.6­fold, 3.0­fold, and 2.4-fold QoL-W deterioration within 4, 4-12, and >12 weeks post-infection (p < 0.05). Subjects with QoL-W decline >12 weeks were younger, mostly women, had more brain fog symptoms, and higher platelet counts. Multivariable models with self-reported brain fog symptoms (responding coherently and recalling recent information), age, and sex exhibited good discriminatory power for QoL-W impairment (area under the receiver operating characteristic curve 0.846, 95% CI: 0.780-0.912). CONCLUSIONS: This study highlighted that in non-high-risk subjects hospitalized during the first 2 pandemic's waves: 1) brain fog was common, affecting nearly half of individuals, and impacting QoL-W >12 weeks after initial infection, 2) after 3 months of COVID-19 onset, the decline in QoL-W was primarily attributed to brain fog symptoms rather than demographic factors, health conditions, admission status, and laboratory findings, 3) components of brain fog, such as answering in an understandable way or recalling new information increased the likelihood of significantly lower QoL-W up to tenfold, 4) biochemical indicators, such as the first hs-cTnI level, might predict the risk of experiencing brain fog symptoms and indirectly decreased QoL-W >12 weeks after COVID-19 onset. Occupational medicine practitioners should pay particular attention to younger and female subjects after COVID-19 complaining of problems with answering questions in understandable way or recalling new information as they have an increased risk of QoL-W impairment. Med Pr Work Health Saf. 2024;75(1):3-17.

Diffusion tensor imaging metrics as natural markers of multiple sclerosis-induced brain disorders with a low Expanded Disability Status Scale score.

Non-invasive and effective differentiation along with determining the degree of deviations compared to the healthy cohort is important in the case of various brain disorders, including multiple sclerosis (MS). Evaluation of the effectiveness of diffusion tensor metrics (DTM) in 3T DTI for recording MS-related deviations was performed using a time-acceptable MRI protocol with unique comprehensive detection of systematic errors related to spatial heterogeneity of magnetic field gradients. In a clinical study, DTMs were acquired in segmented regions of interest (ROIs) for 50 randomly selected healthy controls (HC) and 50 multiple sclerosis patients. Identical phantom imaging was performed for each clinical measurement to estimate and remove the influence of systematic errors using the b-matrix spatial distribution in the DTI (BSD-DTI) technique. In the absence of statistically significant differences due to age in healthy volunteers and patients with multiple sclerosis, the existence of significant differences between groups was proven using DTM. Moreover, a statistically significant impact of spatial systematic errors occurs for all ROIs and DTMs in the phantom and for approximately 90 % in the HC and MS groups. In the case of a single patient measurement, this appears for all the examined ROIs and DTMs. The obtained DTMs effectively discriminate healthy volunteers from multiple sclerosis patients with a low mean score on the Expanded Disability Status Scale. The magnitude of the group differences is typically significant, with an effect size of approximately 0.5, and similar in both the standard approach and after elimination of systematic errors. Differences were also observed between metrics obtained using these two approaches. Despite a small alterations in mean DTMs values for groups and ROIs (1-3 %), these differences were characterized by a huge effect (effect size ∼0.8 or more). These findings indicate the importance of determining the spatial distribution of systematic errors specific to each MR scanner and DTI acquisition protocol in order to assess their impact on DTM in the ROIs examined. This is crucial to establish accurate DTM values for both individual patients and mean values for a healthy population as a reference. This approach allows for an initial reliable diagnosis based on DTI metrics.

Expert opinion of the Heart Rhythm Association of the Polish Cardiac Society and the Polish Neurological Society on evidence-driven implementation of implantable loop recorders in Poland.

Implantable loop recorders (ILR) are considered increasingly helpful in diagnosing cardio-neurological conditions, especially if arrhythmic events are of high clinical importance but are unlikely to be captured by standard methods of electrocardiogram recording due to the low frequency of events and short duration of a single event. The compelling evidence from randomized trials and observational studies strongly supports ILR utilization in patients after cryptogenic stroke or transient ischemic attack and in patients with recurrent transient loss of consciousness of unknown origin. These two groups of patients are expected to gain the most from initiating ILR-driven clinically effective management strategies. Stroke or transient ischemic attack survivors with detected subclinical atrial fibrillation can be switched from antiplatelets to anticoagulants, whilst patients with recurrent syncope may avoid severe injuries and/or substantial impairment of their quality of life. This joint opinion of the Heart Rhythm Association of the Polish Cardiac Society and experts from the Polish Neurological Society summarizes the up-to-date rationale for using ILR in everyday clinical practice and describes the road map for implementing this technology in Poland. Special emphasis is placed on the most recent guidelines issued by both cardiological and neurological scientific societies.

Outcomes following exposure to lacosamide monotherapy during pregnancy and breastfeeding - a prospective case series.

AIM OF THE STUDY: To evaluate the safety of lacosamide (LCM) monotherapy during pregnancy and breastfeeding. MATERIAL AND METHODS: Patients taking LCM monotherapy treated at the university epilepsy clinic were prospectively followed up during pregnancy, delivery, and breastfeeding. Data on seizure frequency, LCM dosage, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation, and development of newborns was collected. RESULTS: Four pregnancies in three patients with refractory focal epilepsy treated with LCM monotherapy were reported. One of these pregnancies ended in a miscarriage during the seventh week of gestation. The average daily LCM dose at the time of conception was 300 mg. Treatment with LCM was continued throughout pregnancy and breastfeeding. The dose of LCM was increased in two pregnancies: in one case following a seizure relapse, and in the other case as a preventive measure to avoid an increase in seizure frequency. Seizure frequency remained stable during pregnancy in two cases. All deliveries were carried out via caesarean section, with an average gestational age at birth of 37.6 weeks. The Apgar score was 10 in all newborns, and no congenital malformations were detected. At the age of 12 months, normal developmental milestones were reached. Infants were breastfed without any complications. CONCLUSIONS AND CLINICAL IMPLICATIONS: This case series adds to a growing body of evidence suggesting the relative safety of LCM monotherapy throughout pregnancy and breastfeeding.

Predictors of good functional outcome in ischaemic stroke patients without delayed neurological improvement after mechanical thrombectomy.

INTRODUCTION: This study aimed to identify predictors of 90-day good functional outcome (GFO) in patients with acute ischaemic stroke (AIS) who were treated with mechanical thrombectomy but did not achieve a delayed neurological improvement (DNI). CLINICAL RATIONALE FOR THE STUDY: In-hospital neurological improvement in patients with AIS is consistently associated with long- -term GFO. Patients who experience neither early nor delayed neurological improvement can still achieve long-term GFO, but predictors of such an outcome have not been studied. MATERIAL AND METHODS: This single-centre retrospective study involved 307 patients with anterior circulation AIS treated with mechanical thrombectomy. Multiple clinical, biochemical, radiological, and treatment-related variables were collected and analysed. DNI on day 7 was defined as at least a 10-point reduction in the National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score < 2. GFO on day 90 was defined as a modified Rankin Scale (mRS) score ≤ 2. We compared the characteristics of patients with and without DNI, with special attention paid to patients who achieved 90-GFO despite a lack of DNI. Multivariate analyses were then performed to establish independent predictors of 90-day GFO among patients without DNI. RESULTS: DNI occurred in 150 out of 307 patients (48.7%) and significantly increased the odds for 90-day GFO (odds ratio [OR]: 13.99; p < 0.001). Among patients without DNI, 41.4% achieved 90-day GFO. Younger age (OR: 0.96; 95% confidence interval [CI]: 0.93-0.99; p = 0.008), lower baseline NIHSS score (OR: 0.80; 95% CI: 0.73-0.89; p < 0.001), treatment with intravenous thrombolysis (OR: 3.06; 95% CI: 1.25-7.49; p = 0.014), lack of an undetermined aetiology (OR: 0.40; 95% CI: 0.16-0.998; p = 0.050), lack of pneumonia (OR: 0.08; 95% CI: 0.02-0.31; p < 0.001), and higher haemoglobin concentration on admission (OR: 1.31; 95% CI: 1.04-1.69; p = 0.024) were identified as predictors of 90-day GFO in this subgroup. CONCLUSION: Almost half of patients with AIS in anterior circulation treated with mechanical thrombectomy experience DNI, which is a good predictor of 90-day GFO. Furthermore, 40% of patients without DNI achieve 90-day GFO which can be independently predicted by younger age, lower baseline NIHSS score, treatment with intravenous thrombolysis, higher haemoglobin concentration on admission, lack of undetermined ischaemic stroke aetiology, and lack of pneumonia.

Acute Ischaemic Stroke in Patients Treated with Direct Oral Anticoagulants: Potential Causes, Clinical Characteristics, and Short-Term Outcomes.

Introduction: Direct oral anticoagulants (DOAC) are the first-line treatment for primary and secondary acute ischaemic stroke (AIS) prevention in patients with nonvalvular atrial fibrillation (NVAF), but a significant percentage of patients develop AIS despite being treated with DOAC. As the number of DOAC-treated patients is growing, so is the number of patients with AIS on DOAC. The aim of the study was to assess the incidence of AIS with prestroke DOAC treatment among patients hospitalised in the University Hospital in Kraków, to analyse the clinical characteristics of AIS occurring in patients on DOAC, and to identify potential causes of treatment ineffectiveness in this group. Materials and Methods: In the study, we included all patients hospitalised in the Department of Neurology of the University Hospital in Kraków within one year (July 2022 to June 2023) with the diagnosis of AIS. The group was divided into two subgroups of patients with and without prestroke DOAC treatment. Based on medical files, we retrospectively analysed the profile of cardiovascular risk factors, stroke severity (assessed with National Institutes of Health Stroke Scale, NIHSS), use of causative stroke treatment and short-term outcomes (defined as NIHSS score, modified Rankin scale (mRS) score at discharge, in-hospital mortality, and secondary intracerebral haemorrhage among patients treated with mechanical thrombectomy, MT). Within the DOAC-treated subgroup, we looked for potential causes of AIS occurring despite DOAC treatment (valvular AF, poor adherence to treatment, underdosing, other prothrombotic conditions, aetiology of stroke other than thromboembolic, and drug-drug interactions). Results: In the study, we included 768 AIS patients. 109 (14.2%) had a history of prestroke DOAC treatment. A potential cause of DOAC treatment failure was identified in the majority of them (n = 63, 57.8%). Patients with prestroke DOAC treatment had worse functional condition before stroke and higher stroke severity on admission but similar short-term outcomes and similar short-term effects of treatment with MT. DOAC (+) and DOAC (-) patients had different profiles of cardiovascular risk factors and different factors associated with short-term outcome. Conclusions and Clinical Implications. A potential cause of AIS occurring in DOAC-treated patients can be identified in most cases and in many of them prevented.

Treatment patterns in women of childbearing age and pregnant women with epilepsy in Poland between the years 2019 and 2022-A nationwide population-based cohort study.

AIM: To describe the antiseizure medications (ASMs) prescription pattern in women of childbearing age (WOCA) and pregnant women with epilepsy in the 2019-2022 period in Poland MATERIALS AND METHODS: The National Health Fund (NHF) databases were analyzed. Women aged 15-49 years were considered as being of childbearing age, while exposure during pregnancy was estimated taking into account 15 months before delivery. ASMs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System, reimbursed by NHF were analyzed. RESULTS: During 2019, 36 784 WOCA and 921 pregnant women filled at least 1 ASM prescription. In 2022, these numbers were 32 304 and 594, respectively. Valproate was the most widely used ASM in WOCA (38.4 %) in 2019, followed by levetiracetam (35.6 %), lamotrigine (30.1 %), and carbamazepine (20.0 %). The percentage of ASM users decreased in 2022 for valproate (32.1 %; p < 0.001) and carbamazepine (17 %; p < 0.001) and increased for levetiracetam (40.8 %; p < 0.001) and lamotrigine (32.7 %; p < 0.001). In 2019 lamotrigine (42.1 %) and levetiracetam (41.5 %) were the most frequently prescribed ASMs to pregnant women. During the study period, a significant increase in prescriptions for levetiracetam was observed (49.5 %; p = 0.003). The proportion of ASMs exposed pregnancies declined for valproate (from 24.7 to 16 %; p < 0.001) and topiramate (from 6.6 to 3.2 %; p = 0.005). The percentage of polytherapy regimens remained stable over the years, both for WOCA (39 %) and pregnant women (32 %). CONCLUSION: Despite the decline in valproate usage, the drug was still among the most commonly prescribed ASMs in women of childbearing age and pregnant women with epilepsy. The awareness of teratogenic risks and new treatment guidelines should be improved in Poland.

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke.

BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.

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.

Reversing dabigatran effect with idarucizumab to enable intravenous thrombolysis in patients with acute ischaemic stroke - a single centre experience.

INTRODUCTION: Our study analysed the safety and effectiveness of idarucizumab in enabling intravenous thrombolysis (IVT) in dabigatran-treated patients with acute ischaemic stroke (AIS). CLINICAL RATIONALE FOR THE STUDY: New oral anticoagulants (NOAC), including dabigatran, are the first-choice treatment option for preventing ischaemic stroke in patients with non-valvular atrial fibrillation (AF). However, a significant percentage of AF patients develops AIS despite NOAC treatment. According to current guidelines, treatment with IVT is contraindicated in patients who have received NOAC within the last 48 hours. Idarucizumab is a fragment of a monoclonal antibody that reverses the anticoagulation effect of dabigatran. The latest research shows that it can enable safe and successful IVT in patients with recent dabigatran intake, but more data is needed to confirm the safety and effectiveness of such treatment. MATERIAL AND METHODS: Our study included dabigatran-treated patients who received idarucizumab to allow AIS treatment with IVT in the University Hospital in Kraków (Poland) from December 2018 to June 2023. We gathered data on their past medical history, stroke severity, course of treatment and outcomes as defined by modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) scores at discharge. A good functional outcome was defined as mRS 0-2 points at discharge. RESULTS: This observational study included 19 patients (13 male and six female) with a median age of 74 (IQR = 13) years. In all patients (100%), the reason for dabigatran treatment was AF. A good functional outcome after treatment (mRS 0-2) was achieved in 68.4% of patients, but mRS was already ≥ 3 points before stroke onset in three (15.8%) patients. Haemorrhagic transformation of stroke occurred in three (15.8%) patients, including symptomatic intracranial haemorrhage in two (10.5%). The mortality rate was 5.3%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study results are in line with previous research on this topic, showing that IVT after idarucizumab can be successfully administered and is reasonably safe in dabigatran-treated patients with AIS.

Safety of brand name to generic substitution of lacosamide in patients with epilepsy - A prospective single-center observational study.

PURPOSE: Lacosamide is a widely used third-generation antiseizure medication. However, there is a lack of evidence regarding the safety of substituting brand-name lacosamide with its generic version. This study aimed to determine the clinical outcomes associated with switching from the brand-name to the generic form of lacosamide (LCM) in patients with epilepsy. METHODS: This prospective observational study involved patients undergoing treatment with LCM at the university epilepsy clinic. In 2018, the price of the brand-name LCM in Poland increased up to 110-fold compared to generic products. Anticipating that most patients would opt to switch to the generic formulations due to financial constraints, we chose to follow up them prospectively to assess the safety of transitioning from the brand-name to the generic form of LCM. RESULTS: A total of 81 patients, aged 18-62 years, diagnosed with focal epilepsy and undergoing LCM treatment at our institution, decided to switch from the brand-name (Vimpat) to generic variations (Lacosamide TEVA, Lacosamide Glenmark, and Lacosamide Accord). Following the switch, no significant difference was observed in terms of seizure frequency before and after (p = 0.55, Wilcoxon signed-rank test). Subsequently, adverse events were recorded in four patients (4.9%) during the initial follow-up visit post-switch, including somnolence (2 patients) and dizziness (2 patients). Notably, all adverse events resolved by the second follow-up visit without necessitating treatment modification. Importantly, no patient switched back to brand-name medication CONCLUSION: The generic substitution of lacosamide was found to be generally safe in our study. Nonetheless, to confirm our findings, larger prospective studies are required.

The Relationships between Cerebrospinal Fluid Glial (CXCL12, CX3CL, YKL-40) and Synaptic Biomarkers (Ng, NPTXR) in Early Alzheimer's Disease.

In addition to amyloid and tau pathology in the central nervous system (CNS), inflammatory processes and synaptic dysfunction are highly important mechanisms involved in the development and progression of dementia diseases. In the present study, we conducted a comparative analysis of selected pro-inflammatory proteins in the CNS with proteins reflecting synaptic damage and core biomarkers in mild cognitive impairment (MCI) and early Alzheimer's disease (AD). To our knowledge, no studies have yet compared CXCL12 and CX3CL1 with markers of synaptic disturbance in cerebrospinal fluid (CSF) in the early stages of dementia. The quantitative assessment of selected proteins in the CSF of patients with MCI, AD, and non-demented controls (CTRL) was performed using immunoassays (single- and multiplex techniques). In this study, increased CSF concentration of CX3CL1 in MCI and AD patients correlated positively with neurogranin (r = 0.74; p < 0.001, and r = 0.40; p = 0.020, respectively), ptau181 (r = 0.49; p = 0.040), and YKL-40 (r = 0.47; p = 0.050) in MCI subjects. In addition, elevated CSF levels of CXCL12 in the AD group were significantly associated with mini-mental state examination score (r = -0.32; p = 0.040). We found significant evidence to support an association between CX3CL1 and neurogranin, already in the early stages of cognitive decline. Furthermore, our findings indicate that CXCL12 might be a useful marker for tract severity of cognitive impairment.

Significance of Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) for the Monitoring of Treatment Response to Cyclosporine in Patients with Psoriasis.

Neutrophil gelatinase-associated lipocalin (NGAL) may promote development of inflammation in psoriasis, whereas proprotein convertase subtilisin/kexin type 9 (PCSK9) may account for dyslipidemia in some psoriatic patients. The aim of the study was to analyze the influence of cyclosporine therapy on serum levels of NGAL and PCSK9 in patients with psoriasis vulgaris. METHODS: Serum samples were obtained before and after three months cyclosporine therapy. Patients were grouped into responders and non-responders to cyclosporine depending on whether they achieved at least 50% reduction of Psoriatic Activity Score Index (PASI), or not. Serum levels of PCSK9 and NGAL were assayed using commercially available ELISA tests. Lipid levels were measured with an enzymatic method. RESULTS: There were 40 patients enrolled. A significant decrease in serum NGAL level was seen in cyclosporine responders. No similar dependance was found for PCSK9. Serum PCSK9 concentration correlated with total cholesterol (TChol) and LDL at baseline and after three month treatment. CONCLUSIONS: Cyclosporine therapy contributes to the reduction of the NGAL serum but not the PCSK9 concentration. Correlation between the PCSK9 serum level and TChol as well as LDL concentration may help to understand drug induced dyslipidemia after cyclosporine.