Publications by authors named "Agnieszka Slowik"

261 Publications

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

Eur J Neurol 2021 Oct 15. Epub 2021 Oct 15.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.

Background: Delirium is a serious complication after stroke. It remains unclear if different motor subtypes of delirium are associated with diverse risk factors and outcomes. We aimed to investigate if delirium subtypes differ in predisposing factors, clinical characteristics and outcomes.

Methods: We prospectively included 698 patients with ischemic stroke or TIA (median age: 73; 53.7% female). We examined core features of delirium during the first 7 days after admission. We used DSM-5 criteria for delirium. We compared pre-stroke characteristics among different delirium subtypes and used logistic regression and Cox hazard models to explore the association between delirium, functional outcome, and death.

Results: We diagnosed hyperactive, hypoactive and mixed delirium in 28, 75 and 66 patients, respectively. Patients with hyperactive delirium had less severe neurological deficit on admission and more often had TIA compared with patients with hypoactive and mixed delirium. Compared with patients with hypoactive delirium, those with hyperactive delirium more often suffered from of irritability/liability 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 was 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/liability. All three motor subtypes of delirium are associated with poor outcome, although hyperactive delirium seems to have less unfavorable prognosis.
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http://dx.doi.org/10.1111/ene.15144DOI Listing
October 2021

Neurogranin and Neuronal Pentraxin Receptor as Synaptic Dysfunction Biomarkers in Alzheimer's Disease.

J Clin Med 2021 Oct 2;10(19). Epub 2021 Oct 2.

Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland.

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer's disease (AD). It seems that by assessing proteins related to synapses, one may reflect their dysfunction and improve the understanding of neurobiological processes in the early stage of the disease. To our best knowledge, this is the first study that analyzes the CSF concentrations of two synaptic proteins together, such as neurogranin (Ng) and neuronal pentraxins receptor (NPTXR) in relation to neurochemical dementia biomarkers in Alzheimer's disease.

Methods: Ng, NPTXR and classical AD biomarkers concentrations were measured in the CSF of patients with AD and non-demented controls (CTRL) using an enzyme-linked immunosorbent assay (ELISA) and Luminex xMAP technology.

Results: The CSF level of Ng was significantly higher, whereas the NPTXR was significantly lower in the AD patients than in cognitively healthy controls. As a first, we calculated the NPTXR/Ng ratio as an indicator of synaptic disturbance. The patients with AD presented a significantly decreased NPTXR/Ng ratio. The correlation was observed between both proteins in the AD and the whole study group. Furthermore, the relationship between the Ng level and pTau181 was found in the AD group of patients.

Conclusions: The Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers reflecting pathological changes in AD.
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http://dx.doi.org/10.3390/jcm10194575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509697PMC
October 2021

The Need for New Biomarkers to Assist with Stroke Prevention and Prediction of Post-Stroke Therapy Based on Plasma-Derived Extracellular Vesicles.

Biomedicines 2021 Sep 15;9(9). Epub 2021 Sep 15.

Department of Neurology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.

The risk of having a stroke event doubles each decade after the age of 55. Therefore, it is of great interest to develop neurorestorative therapies of stroke which occurs mostly in elderly people. However, to date, patients at risk for these sequels of stroke are not duly diagnosed and treated due to the lack of reliable biomarkers. Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are shed by the brain cells and are able to cross the blood-brain barrier and enter the blood stream; thus, they may be used to interrogate molecular and cellular events in the brain damaged area. In this review, we summarize the major molecular and cellular responses of astroglia and neurons to cerebral ischemia and assess their impact on post-stroke recovery and rehabilitation. In particular, we ask if EVs secreted by brain cells are responses to cerebral ischemia, and they may shed new light on the interplay between exosomes-mediated interactions between brain cells and the question of how to exploit it in order to predict the individual course of the disease and to introduce specific preventive or therapeutic strategies. Given these findings, we are left with two options: either to (i) transplant neuronal precursors into the damaged cortical area or (ii) to covert abundantly present proliferating astrocytes in the perilesional area into neurons by using recently developed genetic technologies. However, given the complexity of molecular and cellular responses to cerebral ischemia and our limited capabilities to restore brain structure and function, we are left with only one realistic aim: to invest more in prevention.
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http://dx.doi.org/10.3390/biomedicines9091226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466486PMC
September 2021

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke.

Front Neurol 2021 10;12:700616. Epub 2021 Sep 10.

Centogene AG, Rostock, Germany.

To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to-6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), < 0.01, respectively]. The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.
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http://dx.doi.org/10.3389/fneur.2021.700616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461233PMC
September 2021

Gender-Related Differences in Prodromal Multiple Sclerosis Characteristics: A 7-Year Observation Study.

J Clin Med 2021 Aug 26;10(17). Epub 2021 Aug 26.

Department of Neurology, Medical University of Lublin, 20-090 Lublin, Poland.

Increasing evidence supports the observation that multiple sclerosis (MS) has a preclinical period, with various prodromal signs and symptoms more frequently represented in patients with confirmed MS many years later. Considering the apparent gender differences in the incidence and clinical course of MS, it remains unclear whether it could be reflected in prodromal symptom features. This study aimed to compare a broad spectrum of prodromal signs and symptoms between males and females in the 7-year period before the definite diagnosis of MS. Data came from the central register of the national payer of services, financed under the public healthcare system in Poland. They covered a 7-year period of patient health record claims, from 2009 to 2016. The following groups of symptoms were significant with women: musculoskeletal ( < 0.001), ophthalmic ( < 0.001), laryngological ( < 0.001), digestive system ( < 0.001), urinary tract ( < 0.001), mental ( < 0.001), cardiovascular ( < 0.001), complaints and headaches ( < 0.001). There was also a weak correlation with head injuries ( = 0.03) while dermatological and reproductive system complaints did not appear to be significant ( < 0.05). For males, the following groups of symptoms were significant: musculoskeletal ( < 0.001), ophthalmic ( < 0.001), laryngological ( = 0.007), cardiovascular system symptoms ( < 0.001), and headaches ( < 0.001). Interestingly, reproductive system problems were overrepresented in the male population ( = 0.008). There was no significant correlation with MS risk for dermatological, digestive, urinary, and mental complaints. Similarly, head injuries were not significant. Our results shed more light on well-known differences in the epidemiological and clinical characteristics between sexes in multiple sclerosis, and show differences in prodromal complaints before MS onset.
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http://dx.doi.org/10.3390/jcm10173821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432063PMC
August 2021

Venous return in acute ischaemic stroke patients measured during computed tomography angiography of head and neck.

Neurol Neurochir Pol 2021 Sep 3. Epub 2021 Sep 3.

Chair of Radiology Jagiellonian University Medical College, 19 Kopernika St., 31-501 Krakow, Poland.

Introduction: The aim of this study was to analyse the general features and usefulness of the time elapsed between the start of contrast agent infusion and its appearance in the aortic arch in acute ischaemic stroke patients subjected to baseline computed tomographic angiography. This is, to the best of our knowledge, the first study of this parameter in a clinical context. We will refer to it hereafter as 'needle-to-aorta delay' (NAD).

Material And Methods: The following were recorded: the time it took iodinated contrast media to reach the aorta, the site of occlusion, and automatic perfusion assessments of infarct and salvageable tissue volumes. Demographic data such as age and sex, comorbidities, and clinical factors including heart rate, blood pressure, time elapsed from symptom onset, initial stroke severity, and course of disease, were also assessed.

Results: We analysed 252 cases of stroke. NAD correlated with tissue at risk volume, and was greater for patients with hypertension and atrial fibrillation. The observed time was significantly shorter with less favourable core-to-penumbra ratios. No link was found between NAD and either the rate of infarct progression or the long-term clinical result.

Conclusions: Although no clinical benefit was proven as a result of measuring the time it took contrast media to reach the aorta, our study implies that not only is the brain subject to circulation, but it may also affect its functioning.
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http://dx.doi.org/10.5603/PJNNS.a2021.0060DOI Listing
September 2021

Onabotulinumtoxin A (ONA-BoNT/A) in the treatment of chronic migraine.

Neurol Neurochir Pol 2021 Sep 3. Epub 2021 Sep 3.

Department of Neurology, Stroke and Neurorehabilitation, Medical University of Lodz, Poland.

Migraine is a common primary headache disease, which reduces quality of life. About 8% of migraineurs suffer from chronic migraine (CM), which is the most severe and troublesome type. It has been proven that onabotulinumtoxinA (ONA-BoNT/A) significantly improves CM, presumably inhibiting the release of calcitonin gene-related peptide (CGRP) and other neurotransmitters from c-fibres endings, and thus decreasing activation of nociceptive pathways and transmission of pain. The aim of this position paper was to assess the place of ONA-BoNT/A for the prophylaxis of CM in adults. The authors have compared the efficacy, safety and tolerance of the toxin to those of classical oral preventive therapies as well as to recently introduced anti-CGRP-pathway monoclonal antibodies. The results of randomised controlled studies of ONA-BoNT/A have been compared to open label (real world practice) trials.
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http://dx.doi.org/10.5603/PJNNS.a2021.0061DOI Listing
September 2021

Accelerating Prediction of Malignant Cerebral Edema After Ischemic Stroke with Automated Image Analysis and Explainable Neural Networks.

Neurocrit Care 2021 Aug 20. Epub 2021 Aug 20.

Department of Neurology, Washington University in St. Louis School of Medicine, 660 S Euclid Avenue, Campus, Box 8111, St. Louis, MO, 63110, USA.

Background: Malignant cerebral edema is a devastating complication of stroke, resulting in deterioration and death if hemicraniectomy is not performed prior to herniation. Current approaches for predicting this relatively rare complication often require advanced imaging and still suffer from suboptimal performance. We performed a pilot study to evaluate whether neural networks incorporating data extracted from routine computed tomography (CT) imaging could enhance prediction of edema in a large diverse stroke cohort.

Methods: An automated imaging pipeline retrospectively extracted volumetric data, including cerebrospinal fluid (CSF) volumes and the hemispheric CSF volume ratio, from baseline and 24 h CT scans performed in participants of an international stroke cohort study. Fully connected and long short-term memory (LSTM) neural networks were trained using serial clinical and imaging data to predict those who would require hemicraniectomy or die with midline shift. The performance of these models was tested, in comparison with regression models and the Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score, using cross-validation to construct precision-recall curves.

Results: Twenty of 598 patients developed malignant edema (12 required surgery, 8 died). The regression model provided 95% recall but only 32% precision (area under the precision-recall curve [AUPRC] 0.74), similar to the EDEMA score (precision 28%, AUPRC 0.66). The fully connected network did not perform better (precision 33%, AUPRC 0.71), but the LSTM model provided 100% recall and 87% precision (AUPRC 0.97) in the overall cohort and the subgroup with a National Institutes of Health Stroke Scale (NIHSS) score ≥ 8 (p = 0.0001 vs. regression and fully connected models). Features providing the most predictive importance were the hemispheric CSF ratio and NIHSS score measured at 24 h.

Conclusions: An LSTM neural network incorporating volumetric data extracted from routine CT scans identified all cases of malignant cerebral edema by 24 h after stroke, with significantly fewer false positives than a fully connected neural network, regression model, and the validated EDEMA score. This preliminary work requires prospective validation but provides proof of principle that a deep learning framework could assist in selecting patients for surgery prior to deterioration.
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http://dx.doi.org/10.1007/s12028-021-01325-xDOI Listing
August 2021

Multiple sclerosis incidence and prevalence in Poland: Data from administrative health claims.

Mult Scler Relat Disord 2021 Oct 22;55:103162. Epub 2021 Jul 22.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland; Department of Neurology, University Hospital in Krakow, Krakow, Poland.

Background: The detailed data concerning multiple sclerosis (MS) epidemiology in Poland are based on studies from few and less populated provinces. Therefore, we evaluated MS incidence and prevalence in Poland using electronic administrative health claims (AHCs) from the National Health Fund.

Methods: We retrospectively analyzed the AHC financial database collected from 2009 to 2019, encompassing all patients using public health resources. Three different algorithms for identification of MS cases were used: based on studies performed in German population (type 1), tested in the United States (type 2), and one created for the purpose of this study (type 3) that required at least 3 AHCs since 2009 with G35 ICD-10 diagnosis in outpatient specialist care, during hospitalization, and/or at rehabilitation service in any combination within maximally 3 years between the first and the last AHC, and provided that at least one AHC was either in neurological outpatient care or during hospitalization at a neurological ward or prescription of disease-modifying therapy. The American algorithm (type 2) required 3 AHCs within the analyzed year, while the German algorithm (type 1) required only one AHC in the analyzed year.

Results: According to the type 3 algorithm, age-adjusted MS incidence and prevalence in 2019 was 6.6 and 131.2 / 100,000 inhabitants, respectively. From 2014 to 2019, the significant trend in increasing prevalence and decreasing incidence of MS was observed (p<0.001). Median age of prevalent MS patients was 50 years (interquartile range, IQR 39-61) whereas median age of incident MS cases was 37 years (IQR 28-48). Female-to-male ratio in MS patients was 2.4. According to the type 1 algorithm, age-adjusted MS incidence and prevalence in 2019 was 11.6 and 244.9 / 100,000 inhabitants, respectively. Use of the type 2 algorithm resulted in estimated age-adjusted MS incidence and prevalence values in 2019 of 6.2 and 120.1 / 100,000 inhabitants, respectively.

Conclusions: Multiple sclerosis incidence and prevalence in Poland are higher than previously reported and similar to the numbers shown for central European countries.
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http://dx.doi.org/10.1016/j.msard.2021.103162DOI Listing
October 2021

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

Pol J Radiol 2021 11;86:e344-e352. Epub 2021 Jun 11.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.

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.
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http://dx.doi.org/10.5114/pjr.2021.107065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297478PMC
June 2021

MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes.

Front Neurosci 2021 12;15:691244. Epub 2021 Jul 12.

Department of Neurology, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO, United States.

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes.

Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask-WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA).

Results: Radiomic features were predictive of WMH burden ( = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected -values < 0.001, -value = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes.

Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients' brain health.
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http://dx.doi.org/10.3389/fnins.2021.691244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312571PMC
July 2021

Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis.

J Clin Med 2021 Jul 16;10(14). Epub 2021 Jul 16.

Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, 08025 Barcelona, Spain.

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, -value 3.90 × 10) located in the gene and a suggestive variant (rs13297983: beta 0.07, -value 6.10 × 10) located in associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-β, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.
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http://dx.doi.org/10.3390/jcm10143137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305811PMC
July 2021

Fatty Acid Binding Protein 3 (FABP3) and Apolipoprotein E4 (ApoE4) as Lipid Metabolism-Related Biomarkers of Alzheimer's Disease.

J Clin Med 2021 Jul 6;10(14). Epub 2021 Jul 6.

Department of Neurodegeneration Diagnostics, Medical University of Bialystok, 15-269 Bialystok, Poland.

Background: Lipid metabolism-related biomarkers gain increasing researchers interest in the field of neurodegenerative disorders. Mounting evidence have indicated the role of fatty acid-binding proteins and pathology lipid metabolism in Alzheimer's Disease (AD). The imbalance of fatty acids (FA) and lipids may negatively affect brain functions related to neurodegenerative disorders. The ApoE4 and FABP3 proteins may reflect processes leading to neurodegeneration. This study aimed to evaluate the relationship between the CSF levels of FABP3 and ApoE4 proteins and cognitive decline as well as the diagnostic performance of these candidate biomarkers in AD and mild cognitive impairment (MCI).

Methods: A total of 70 subjects, including patients with AD, MCI, and non-demented controls, were enrolled in the study. CSF concentrations of FABP3 and ApoE4 were measured using immunoassay technology.

Results: Significantly higher CSF concentrations of FABP3 and ApoE4 were observed in AD patients compared to MCI subjects and individuals without cognitive impairment. Both proteins were inversely associated with Aβ42/40 ratio: ApoE4 (rho = -0.472, < 0.001), and FABP3 (rho = -0.488, < 0.001) in the whole study group, respectively. Additionally, FABP3 was negatively correlated with Mini-Mental State Examination score in the whole study cohort (rho = -0.585 < 0.001).

Conclusion: Presented results indicate the pivotal role of FABP3 and ApoE4 in AD pathology as lipid-related biomarkers, but studies on larger cohorts are needed.
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http://dx.doi.org/10.3390/jcm10143009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303862PMC
July 2021

Fasting Normoglycemia after Intravenous Thrombolysis Predicts Favorable Long-Term Outcome in Non-Diabetic Patients with Acute Ischemic Stroke.

J Clin Med 2021 Jul 6;10(14). Epub 2021 Jul 6.

Department of Neurology, Jagiellonian University Medical College, 30-688 Krakow, Poland.

Background: Only a few studies evaluated the role of fasting glucose levels after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Importantly, formal analysis concerning the prognostic role of fasting glucose levels in these patients with and without diabetes mellitus (DM) was not performed. Therefore, we assessed whether fasting normoglycemia (FNG) next morning after AIS treated with IVT was associated with 90-day functional outcome in diabetic and non-diabetic patients.

Methods: We retrospectively analyzed 362 AIS patients treated with IVT at The University Hospital in Krakow. FNG was defined as glucose below 5.5 mmol/L. A favorable outcome was defined as modified Rankin score (mRS) of 0-2 at day 90 after AIS onset.

Results: At 3-month follow-up, FNG was associated with favorable outcome (87.5% vs. 60.8%, < 0.001) and decreased risk of death (3.1% vs. 18.1%, = 0.002). Independent predictors of a favorable outcome for the whole group were: younger age (HR 0.92, 95%CI 0.89-0.95), lower NIHSS score after IVT (HR 0.70, 95%CI 0.65-0.76), lower maximal systolic blood pressure within 24 h after IVT (HR 0.92, 95%CI 0.89-0.95) and FNG (HR 4.12, 95%CI 1.38-12.35). Association between FNG and mortality was found in univariable (HR 1.47, 95%CI 0.04-0.62) but not in multivariable analysis (HR 0.23, 95%CI 0.03-1.81). In subgroup analyses, FNG was an independent predictor of favorable outcome (HR 5.96, 95%CI 1.42-25.1) only in patients without DM.

Conclusions: FNG next morning after IVT is an independent protective factor for a favorable long-term outcome in non-diabetic AIS patients.
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http://dx.doi.org/10.3390/jcm10143005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306150PMC
July 2021

Transcranial Magnetic Stimulation as a Diagnostic and Therapeutic Tool in Various Types of Dementia.

J Clin Med 2021 Jun 28;10(13). Epub 2021 Jun 28.

Department of Neurology, Jagiellonian University Medical College, Jakubowskiego 2, 30-688 Krakow, Poland.

Dementia is recognized as a healthcare and social burden and remains challenging in terms of proper diagnosis and treatment. Transcranial magnetic stimulation (TMS) is a diagnostic and therapeutic tool in various neurological diseases that noninvasively investigates cortical excitability and connectivity and can induce brain plasticity. This article reviews findings on TMS in common dementia types as well as therapeutic results. Alzheimer's disease (AD) is characterized by increased cortical excitability and reduced cortical inhibition, especially as mediated by cholinergic neurons and as documented by impairment of short latency inhibition (SAI). In vascular dementia, excitability is also increased. SAI may have various outcomes, which probably reflects its frequent overlap with AD. Dementia with Lewy bodies (DLB) is associated with SAI decrease. Motor cortical excitability is usually normal, reflecting the lack of corticospinal tract involvement. DLB and other dementia types are also characterized by impairment of short interval intracortical inhibition. In frontotemporal dementia, cortical excitability is increased, but SAI is normal. Repetitive transcranial magnetic stimulation has the potential to improve cognitive function. It has been extensively studied in AD, showing promising results after multisite stimulation. TMS with electroencephalography recording opens new possibilities for improving diagnostic accuracy; however, more studies are needed to support the existing data.
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http://dx.doi.org/10.3390/jcm10132875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267667PMC
June 2021

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns.

Nat Commun 2021 06 2;12(1):3289. Epub 2021 Jun 2.

Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA.

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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http://dx.doi.org/10.1038/s41467-021-23492-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172535PMC
June 2021

Neurological symptoms in hospitalised patients with COVID-19 and their association with in-hospital mortality.

Neurol Neurochir Pol 2021 26;55(3):314-321. Epub 2021 May 26.

Jagiellonian University Medical College, Department of Internal Medicine and Gerontology, Krakow, Poland.

Objectives: To evaluate the spectrum of neurological symptoms in patients with COVID-19 during the first 14 days of hospitalisation and its association with in-hospital mortality.

Material And Methods: We included 200 patients with RT-PCR-confirmed COVID-19 admitted to University Hospital in Krakow, Poland. In 164 patients, a detailed questionnaire concerning neurological symptoms and signs was performed prospectively within 14 days of hospitalisation. In the remaining 36 patients, such questionnaires were completed retrospectively based on daily observations in the Department of Neurology.

Results: During hospitalisation, 169 patients (84.5%) experienced neurological symptoms; the most common were: fatigue (62.5%), decreased mood (45.5%), myalgia (43.5%), and muscle weakness (42.5%). Patients who died during hospitalisation compared to the remainder were older (79 [70.5-88.5] vs. 63.5 [51-77] years, p = 0.001), and more often had decreased level of consciousness (50.0% vs. 9.3%, p < 0.001), delirium (33.3% vs. 4.4%, p < 0.001), arterial hypotension (50.0% vs. 19.6%, p = 0.005) or stroke during (18.8% vs. 3.3%, p = 0.026) or before hospitalisation (50.0% vs. 7.1, p < 0.001), whereas those who survived more often suffered from headache (42.1% vs. 0%, p = 0.012) or decreased mood (51.7% vs. 0%, p = 0.003).

Conclusions: Most hospitalised patients with COVID-19 experience neurological symptoms. Decreased level of consciousness, delirium, arterial hypotension, and stroke during or before hospitalisation increase the risk of in-hospital mortality.
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http://dx.doi.org/10.5603/PJNNS.a2021.0039DOI Listing
July 2021

Hemispheric CSF volume ratio quantifies progression and severity of cerebral edema after acute hemispheric stroke.

J Cereb Blood Flow Metab 2021 May 20:271678X211018210. Epub 2021 May 20.

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.

As swelling occurs, CSF is preferentially displaced from the ischemic hemisphere. The ratio of CSF volume in the stroke-affected hemisphere to that in the contralateral hemisphere may quantify the progression of cerebral edema. We automatically segmented CSF from 1,875 routine CTs performed within 96 hours of stroke onset in 924 participants of a stroke cohort study. In 737 subjects with follow-up imaging beyond 24-hours, edema severity was classified as affecting less than one-third of the hemisphere (CED-1), large hemispheric infarction (LHI, over one-third the hemisphere), without midline shift (CED-2) or with midline shift (CED-3). Malignant edema was LHI resulting in deterioration, requiring osmotic therapy, surgery, or resulting in death. Hemispheric CSF ratio was lower on baseline CT in those with LHI (0.91 vs. 0.97, p < 0.0001) and decreased more rapidly in those with LHI who developed midline shift (0.01 per hour for CED-3 vs. 0.004/hour CED-2). The ratio at 24-hours was lower in those with midline shift (0.41, IQR 0.30-0.57 vs. 0.66, 0.56-0.81 for CED-2). A ratio below 0.50 provided 90% sensitivity, 82% specificity for predicting malignant edema among those with LHI (AUC 0.91, 0.85-0.96). This suggests that the hemispheric CSF ratio may provide an accessible early biomarker of edema severity.
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http://dx.doi.org/10.1177/0271678X211018210DOI Listing
May 2021

COVID-19 among patients with epilepsy: Risk factors and course of the disease.

Epilepsy Behav 2021 07 24;120:107996. Epub 2021 Apr 24.

Jagiellonian University Medical College, Faculty of Medicine, Department of Neurology, Krakow, Poland.

Introduction: The study assessed the prevalence and risk factors for SARS-CoV-2 infection in patients with epilepsy (PWE). Additionally, the course of COVID-19 and its impact on seizure control was investigated.

Material And Methods: Subjects with definite (confirmed by positive RT-PCR nasopharyngeal swab or serum anti-SARS-CoV-2 antibodies) and probable COVID-19 were identified via telephone survey among PWE treated at the university epilepsy clinic.

Results: Of 252 screened subjects, 17 (6.7%) had definite and 14 (5.5%) probable COVID-19. The percentage of PWE with definite COVID-19 was much higher than the percentage of subjects with confirmed COVID-19 in Polish general population (3.65%). In the heterogenous population of PWE, including patients with drug-resistant epilepsy, physical/intellectual disability, and comorbidities, we were not able to identify any risk factors for contracting COVID-19. The course of infection was mild or moderate in all subjects, not requiring oxygen therapy or respiratory support. The most common symptoms were fever, fatigue, headaches, muscle aches, and loss of smell/taste and continued for approximately 7-21 days, except for loss of smell/taste which lasted usually several weeks. Seizure exacerbation was noted in only one pregnant patient with confirmed COVID-19 and it was likely related to decreased serum level of levetiracetam in the third trimester.

Conclusion: The study provided reassuring findings related to the low risk of seizure exacerbation in PWE during the course of COVID-19. Patients with epilepsy may be at increased risk of SARS-CoV-2 infection. Epilepsy characteristics are not likely to modify the risk of COVID-19.
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http://dx.doi.org/10.1016/j.yebeh.2021.107996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064834PMC
July 2021

4C Mortality Score correlates with in-hospital functional outcome after COVID-19-associated ischaemic stroke.

Neurol Neurochir Pol 2021 5;55(3):295-299. Epub 2021 May 5.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.

Aim Of The Study: The 4C Mortality Score was created to predict mortality in hospitalised patients with COVID-19 and has to date been evaluated only in respiratory system disorders. The aim of this study was to investigate its application in patients with COVID-19-associated acute ischaemic stroke (AIS).

Clinical Rationale For Study: COVID-19 is a risk factor for AIS. COVID-19-associated AIS results in higher mortality and worse functional outcome. Predictors of functional outcome in COVID-19-associated AIS are required.

Materials And Methods: This was a retrospective observational study of patients with AIS hospitalised in seven neurological wards in Małopolska Voivodship (Poland) between August and December 2020. We gathered data concerning the patients' age, sex, presence of cardiovascular risk factors, type of treatment received, and the presence of stroke-associated infections (including pneumonia, urinary tract infection and infection of unknown source). We calculated 4C Mortality Score at stroke onset, and investigated whether there was a correlation with neurological deficit measured using the National Health Institute Stroke Scale (NIHSS) and functional outcome assessed using the modified Rankin Scale (mRS) at discharge.

Results: The study included 52 patients with COVID-19-associated AIS. The 4C Mortality Score at stroke onset correlated with mRS (rs = 0.565, p < 0.01) at discharge. There was also a statistically significant difference in the mean 4C Mortality Score between patients who died and patients who survived the stroke (13.08 ± 2.71 vs. 9.85 ± 3.47, p = 0.04).

Conclusions And Clinical Implications: 4C Mortality Score predicts functional outcome at discharge in COVID-19-associated AIS patients.
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http://dx.doi.org/10.5603/PJNNS.a2021.0037DOI Listing
July 2021

Association between cardiovascular disease, cardiovascular drug therapy, and in-hospital outcomes in patients with COVID-19: data from a large single-center registry in Poland.

Kardiol Pol 2021 20;79(7-8):773-780. Epub 2021 May 20.

Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, Kraków, Poland.

Background: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19.

Aims: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19.

Methods: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020.

Results: 1729 patients (median interquartile range age 63 [50-75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, β-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3-9.6), male sex (OR, 1.4; 95% CI, 1.1-2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1-2.1), and HF (OR, 2.3; 95% CI, 1.5-3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3-0.6), β-blockers (OR, 0.6; 95% CI, 0.4-0.9), statins (OR, 0.5; 95% CI, 0.3-0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4-0.9) was associated with lower risk of death.

Conclusions: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.
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http://dx.doi.org/10.33963/KP.15990DOI Listing
September 2021

Modified Rio Score with Platform Therapy Predicts Treatment Success with Fingolimod and Natalizumab in Relapsing-Remitting Multiple Sclerosis Patients.

J Clin Med 2021 Apr 22;10(9). Epub 2021 Apr 22.

Department of Neurology, Medical University of Lublin, Jaczewskiego 8, 20-054 Lublin, Poland.

Background: Reliable markers of disease outcomes in multiple sclerosis (MS) would help to predict the response to treatment in patients treated with high efficacy drugs. No evidence of disease activity (NEDA) has become a treatment goal whereas the modified Rio score (MRS) predicts future suboptimal responders to treatment. The aim of our study was to identify factors that would predict poor response to treatment with natalizumab and fingolimod.

Methods: In the multicenter prospective trial, 336 subjects were enrolled, initiating therapy with natalizumab ( = 135) or fingolimod ( = 201). Data on relapse rate, the expanded disability status scale, and MRI results were collected, and MRS was estimated.

Results: NEDA-3 after the first year of therapy was 73.9% for natalizumab and 54.8% for fingolimod ( < 0.0001). Patients with MRS = 0 in the last year on platform therapy had the best NEDA-3 (71%) and patients with MRS = 3 had the worst NEDA-3 (41%) in the first year of treatment with the second-line therapy.

Conclusion: We conclude that switching to the second-line therapy should occur earlier to enable better results for patients treated with natalizumab or fingolimod. The outcome on both drugs is better with better neurological conditions and lower MRS of the patient on the platform therapy.
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http://dx.doi.org/10.3390/jcm10091830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122749PMC
April 2021

C-Reactive Protein and White Blood Cell Count in Non-Infective Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

J Clin Med 2021 Apr 10;10(8). Epub 2021 Apr 10.

Department of Neurology, Jagiellonian University Medical College, 31-688 Krakow, Poland.

Previous studies on inflammatory biomarkers in acute ischemic stroke (AIS) produced divergent results. We evaluated whether C-reactive protein (CRP) and white blood cell count (WBC) measured fasting 12-24 h after intravenous thrombolysis (IVT) were associated with outcome in AIS patients without concomitant infection. The study included 352 AIS patients treated with IVT. Excluded were patients with community-acquired or nosocomial infection. Outcome was measured on discharge and 90 days after stroke onset with the modified Rankin scale (mRS) and defined as poor outcome (mRS 3-6) or death (mRS = 6). Final analysis included 158 patients (median age 72 years (interquartile range 63-82), 53.2% ( = 84) women). Poor outcome on discharge and at day 90 was 3.8-fold and 5.8-fold higher for patients with CRP ≥ 8.65 mg/L (fifth quintile of CRP), respectively, compared with first quintile (<1.71 mg/L). These results remained significant after adjustment for potential confounders (odds ratio (OR) on discharge = 10.68, 95% CI: 2.54-44.83, OR at day 90 after stroke = 7.21, 95% CI: 1.44-36.00). In-hospital death was 6.3-fold higher for patients with fifth quintile of CRP as compared with first quintile and remained independent from other variables (OR = 4.79, 95% CI: 1.29-17.88). Independent predictors of 90-day mortality were WBC < 6.4 × 10 /L (OR = 5.00, 95% CI: 1.49-16.78), baseline National Institute of Health Stroke Scale (NIHSS) score (OR = 1.13 per point, 95% CI: 1.01-1.25) and bleeding brain complications (OR = 5.53, 95% CI: 1.59-19.25) but not CRP ≥ 8.65 mg/L. Non-infective CRP levels are an independent risk factor for poor short- and long-term outcomes and in-hospital mortality in AIS patients treated with IVT. Decreased WBC but not CRP is a predictor for 90-day mortality.
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http://dx.doi.org/10.3390/jcm10081610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069454PMC
April 2021

Toll-like receptor 4-mediated cytokine synthesis and post-stroke depressive symptoms.

Transl Psychiatry 2021 04 26;11(1):246. Epub 2021 Apr 26.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.

Altered cytokine synthesis thought to contribute to the pathophysiology of post-stroke depression (PSD). Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of this study was to explore the putative association between TLR4-mediated cytokine synthesis and subsequent symptoms of PSD. In total, 262 patients with ischemic stroke and without a history of PSD were included. Depressive symptoms were assessed using the Patient Health Questionnaire-9 in 170 patients on Day 8 and in 146 at 3 months after stroke. Blood samples taken on Day 3 after stroke were stimulated ex vivo with lipopolysaccharide (LPS). Ex vivo synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) and circulating cytokines (TNFα, IL-6, sIL-6R, and IL-1ra) were measured using the enzyme-linked immunoassay or cytometric method. RNA sequencing was used to determine the gene expression profile of LPS-induced cytokines and chemokines. LPS-induced cytokine synthesis and the gene expression of TLR4-dependent cytokines and chemokines did not differ between patients with and without greater depressive symptoms. The plasma level of IL-6, but not TNFα, sIL-6R, and IL-1ra, was higher in patients who developed depressive symptoms at 3 months after stroke (median: 4.7 vs 3.4 pg/mL, P = 0.06). Plasma IL-6 predicted the severity of depressive symptoms at 3 months after stroke (β = 0.42, P = 0.03). In conclusion, TLR4-dependent cytokine synthesis was not associated with greater post-stroke depressive symptoms in this study. Circulating IL-6 might be associated with depressive symptoms occurring at 3 months after stroke.
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http://dx.doi.org/10.1038/s41398-021-01359-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076201PMC
April 2021

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

J Neuroimmunol 2021 07 17;356:577579. Epub 2021 Apr 17.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland. Electronic address:

To explore the role of systemic inflammation in post-stroke delirium, we investigated the level of two inflammatory mediators: high mobility group box 1 (HMGB1) and galectin-3 binding protein (Gal-3BP). Of 571 stroke patients, we compared plasma levels of HMGB1 and Gal-3BP in 79 delirious patients with 81 non-delirious patients matched for age and stroke severity. Delirious patients had higher Gal-3BP level (median: 1440 vs 1053 ng/mL, P < 0.01). An elevated level of Gal-3BP was associated with an increased risk of delirium. HMGB1 levels did not differ between groups. Our results suggest that pro-inflammatory monocytes and macrophages might be involved in delirium pathophysiology.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577579DOI Listing
July 2021

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies - the Polish experience.

Neurol Neurochir Pol 2021 15;55(2):212-222. Epub 2021 Apr 15.

Medical University of Białystok, Poland.

Introduction: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited.

Materials And Methods: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health.

Results: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used.

Conclusions And Clinical Implications: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.
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May 2021

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

J Neural Transm (Vienna) 2021 May 16;128(5):679-686. Epub 2021 Mar 16.

Department of Neurology, Jagiellonian University Medical College, ul. Botaniczna 3, 31-503, Krakόw, Poland.

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.
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http://dx.doi.org/10.1007/s00702-021-02328-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105243PMC
May 2021

Single nucleotide variations in ZBTB46 are associated with post-thrombolytic parenchymal haematoma.

Brain 2021 Sep;144(8):2416-2426

Department of Neurology, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona 08025, Spain.

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 × 10-5 were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 × 10-8) were characterized by in silico functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 × 10-8; odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 × 10-8; OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silico studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment.
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http://dx.doi.org/10.1093/brain/awab090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418348PMC
September 2021

Lipopolysaccharide binding protein and sCD14 as risk markers of stroke-associated pneumonia.

J Neuroimmunol 2021 05 27;354:577532. Epub 2021 Feb 27.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland. Electronic address:

To determine the utility of lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) as risk markers of stroke-associated pneumonia (SAP). We included 331 stroke patients. The plasma levels of LBP (median: 19.4 vs 15.3 μg/mL, P < 0.01) and sCD14 (median: 1.5 vs 1.4 μg/mL, P = 0.04) were elevated in SAP. In multivariate analysis, a higher level of LBP (OR: 1.09, 95%CI: 1.05-1.13), but not sCD14 (OR: 2.16, 0.94-4.97), was associated with SAP. The addition of LBP or sCD14 to the clinical model did not improve its discriminatory ability. Our results suggest the modest value of studied biomarkers for SAP prediction.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577532DOI Listing
May 2021

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

Eur J Neurol 2021 06 9;28(6):1949-1957. Epub 2021 Mar 9.

Department of Neurology, Jagiellonian University Medical College, Krakow, Poland.

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.
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http://dx.doi.org/10.1111/ene.14785DOI Listing
June 2021
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