The association between white matter tract structural connectivity and information processing speed in relapsing-remitting multiple sclerosis.

BACKGROUND: Information processing speed (IPS) deterioration is common in relapsing-remitting multiple sclerosis (RRMS) patients [1] and might severely affect quality of life and occupational activity. However, understanding of its neural substrate is not fully elucidated. We aimed to investigate the associations between MRI-derived metrics of neuroanatomical structures, including the tracts, and IPS. METHODS: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and Color Trails Test (CTT) were used to evaluate IPS in 73 RRMS consecutive patients, all undergoing only interferon beta (IFN-ß) therapy during the study. At the same time, 1.5T MRI including diffusion tensor imaging (DTI) data was acquired for each recruited subject. We analyzed volumetric and diffusion MRI measures (FreeSurfer 6.0) including normalized brain volume (NBV), cortical thickness (thk), white matter hypointensities (WMH), volume (vol), diffusion parameters: mean (MD), radial (RD), axial (AD) diffusivities, and fractional anisotropy (FA) of 18 major white-matter (WM) tracts. Multiple linear regression model with interaction resulted in distinguishing the neural substrate of IPS deficit in the IPS impaired subgroup of patients. RESULTS: The most significant tract abnormalities contributing to IPS deficit were right inferior longitudinal fasciculus (R ILF) FA, forceps major (FMAJ) FA, forceps minor (FMIN) FA, R uncinate fasciculus (UNC) AD, R corticospinal tract (CST) FA, and left superior longitudinal fasciculus FA (L SLFT). Among volumetric MRI metrics, IPS deficit was associated with L and R thalamic vol. and cortical thickness of insular regions. CONCLUSION: In this study, we showed that disconnection of the selected WM tracts, in addition to cortical and deep gray matter (GM) atrophy, might underlie IPS deficit in RRMS patients but more extensive studies are needed for precise associations.

Effect of Glucocorticoid Administration in Intravenous Pulses on Selected Parameters of the Coagulation System.

Background: Changes of the coagulation system are promoted by serious infectious or noninfectious diseases, surgical procedures, and exogenous substances, including drugs. This study aimed to assess the effect of methylprednisolone pulses on selected parameters of the coagulation system. Methods: The study group consisted of patients suffering from multiple sclerosis, thyroid orbitopathy, or sudden sensorineural hearing loss. 48 patients and 20 healthy volunteers were examined. The hemostatic parameters: activity of coagulation factors (VIII, IX, and XI), antithrombin activity, protein C and S activity, and concentration of soluble tissue factor were analyzed at baseline and after 3 g and 5 g of methylprednisolone administration. Results: A statistically significant increase was noted in the activity of all the studied plasma coagulation factors, plasma coagulation inhibitors (except protein S activity), and the concentration of soluble tissue factor after methylprednisolone administration. Conclusion: The glucocorticoids administered in the intravenous pulses of methylprednisolone shift the balance toward thromboembolic complications.

Supine blood pressure normalised by daytime series values is independently associated with ischaemic wake-up stroke.

PURPOSE: Wake-up stroke constitutes up to 1/4 of all ischaemic strokes; however, its pathomechanisms remain largely unknown. Although low nocturnal blood flow may be the underlying cause, little is known about blood pressure (BP) characteristic of wake-up stroke patients. The aim of our study was to look for differences in BP variables between wake-up stroke and known-onset stroke patients and to seek BP indices which could distinguish wake-up stroke patients from other stroke patients. MATERIALS AND METHODS: In the study, we included ischaemic stroke patients in whom office BP measurement and Ambulatory BP monitoring (ABPM) were recorded at day 7, after acute hypertensive response. The daytime period was defined as the interval from 6 a.m. to 10 p.m. From ABPM, we obtained parameters of BP variability. Additionally, we calculated the BP percentage differences defined as (supine office BP-average daytime BP)/average daytime BP for systolic, diastolic, and mean blood pressure. We calculated analogous indices for night-time. The univariate and multivariate relationships between BP variables and wake-up stroke were analysed. RESULTS: Among the recruited 120 patients (aged 61.6 ± 12.3; 88 [73%] males; the baseline National Institutes of Health stroke scale score 4 [3-8]), 36 (30%) had wake-up stroke. In a univariate analysis, the systolic and mean daytime and night-time BP differences were significantly lower in patients with wake-up stroke [(-1.92 (-11.55 to 3.95) vs 4.12 (-2.48 to 11.31), p = 0.006 and -6.20 (-12.32 to 7.42) vs 2.00 (-6.86 to 11.65), p = 0.029 for daytime, respectively; 0.00 (-9.79 to 11.82) vs 9.84 (0.00 to 18.25), p = 0.003 and 0.51 (-8.49 to 12.08) vs 7.82 (-2.47 to 20.39), p = 0.026, for night-time, respectively]. After adjustment for possible confounders, the systolic BP difference remained significantly associated with wake-up stroke (odds ratio = 0.96, 95% confidence interval = 0.92-1.00, p = 0.039). CONCLUSION: The subacute office-ambulatory BP difference including the dynamic (systolic BP), but not static BP component was independently associated with wake-up stroke.

Trends of stroke hospitalisation and fatality rates in young vs. elderly people in Poland during 2010-2019 decade.

INTRODUCTION: Since the turn of the century, epidemiological studies have shown an increase in stroke hospitalisation rates among young adults in contrast to a decline in rates seen among the older population. The aim of the present study was to investigate the trends of stroke hospitalisation rates and case fatality ratios (CFR) over the decade starting in 2010 in different age groups of the Polish population. MATERIAL AND METHODS: The patients were identified on the basis of the Polish National Health Fund that gathers all the data of the Hospital Discharge Registry as well as the National Cause of Death Registry of patients with stroke who were hospitalised between 2010 and 2019 and who were diagnosed according to the International Classification of Diseases - Tenth Revision (ICD-10) with haemorrhagic stroke (HS; codes I61* and I62*) and ischaemic stroke (IS; codes I63*). RESULTS: From a total nationwide cohort of 799,132 stroke patients (86.2% with IS and 13.8% with HS) treated between 2010 and 2019, a group of 22,329 patients (2.79%) aged 18-44 years was selected, among whom 69.6% had IS and 30.4% had HS. We documented a statistically significant increase in the IS hospitalisation rate in young adults alongside a decrease of this rate in those aged > 64. Among young adults with IS, the highest increase (p = 0.001) was observed for those aged 35-44 in 2019 (up to 39.2), and was significant each year starting from 2017 (2017-2019: p < 0.01). In the case of HS, the annual number of patients did not change significantly. In 2019 (compared to 2010), a decrease in 30-day, 90-day and 1-year CFR was noted in all age groups of patients with IS and HS. Stroke aetiology of IS was diagnosed in 60% of patients. More than 40% of patients with IS were discharged with the diagnosis of stroke of unspecified cause. CONCLUSIONS: In the case of IS, opposite trends of hospitalisation rates in younger and older age groups were documented, with the highest increase of IS in patients aged 35-44. A decline in CFR was observed for both IS and HS in all age groups.

EBI2 is expressed in glial cells in multiple sclerosis lesions, and its knock-out modulates remyelination in the cuprizone model.

EBI2 receptor regulates the immune system, and in multiple, sclerosis is upregulated in the central nervous system infiltrating lymphocytes. In newborn EBI2-deficient mice, myelin development is delayed, and its persistent antagonism inhibits remyelination in chemically demyelinated organotypic cerebellar slices. We used the cuprizone model of multiple sclerosis to elucidate the role of central nervous system-expressed EBI2 in de- and remyelination. The wild-type and EBI2 knock-out mice were fed 0.2% cuprizone in chow for 5 weeks and allowed to recover on a normal diet for 2 weeks. The data showed less efficient recovery of myelin, attenuated oligodendrocyte loss, fewer astrocytes and increased total cholesterol levels in the EBI2 knock-out mice after recovery. Moreover, the wild-type mice upregulated EBI2 expression after recovery confirming the involvement of EBI2 signalling during recovery from demyelination in the cuprizone model. The pro-inflammatory cytokine levels were at comparable levels in the wild-type and EBI2 knock-out mice, with only minor differences in TNFα and IL1ß levels either at peak or during recovery. The neuroinflammatory signalling molecules, Abl1 kinase and NFКB1 (p105/p50) subunit, were significantly downregulated in the EBI2 knock-out mice at peak of disease. Immunohistochemical investigations of EBI2 receptor distribution in the central nervous system (CNS) cells in multiple sclerosis (MS) brain revealed strong expression of EBI2 in astrocytes and microglia inside the plaques implicating glia-expressed EBI2 in multiple sclerosis pathophysiology. Taken together, these findings demonstrate the involvement of EBI2 signalling in the recovery from demyelination rather than in demyelination and as such warrant further research into the role of EBI2 in remyelination.

Blood Pressure Management in Acute Ischemic Stroke.

PURPOSE OF REVIEW: Abrupt blood pressure (BP) rise is the most common clinical symptom of acute ischemic stroke (AIS). However, BP alterations during AIS reflect many diverse mechanisms, both stroke-related and nonspecific epiphenomena, which change over time and across patients. While extremes of BP as well as high BP variability have been related with worse outcomes in observational studies, optimal BP management after AIS remains challenging. RECENT FINDINGS: This review discusses the complexity of the factors linking BP changes to the clinical outcomes of patients with AIS, depending on the treatment strategy and local vessel status and, in particular, the degree of reperfusion achieved. The evidence for possible additional clinical markers, including the presence of arterial hypertension, and comorbid organ dysfunction in individuals with AIS, as informative and helpful factors in therapeutic decision-making concerning BP will be reviewed, as well as recent data on neurovascular monitoring targeting person-specific local cerebral perfusion and metabolic demand, instead of the global traditional parameters (BP among others) alone. The individualization of BP management protocols based on a complex evaluation of the homeostatic response to focal cerebral ischemia, including but not limited to BP changes, may be a valuable novel goal proposed in AIS, but further trials are warranted.

The salvageable brain in acute ischemic stroke. The concept of a reverse mismatch: a mini-review.

Recent studies have opened a new era in treatment of acute ischemic stroke, enabling thrombolysis or thrombectomy far beyond the standard therapeutic "time windows". These therapeutic protocols are built on various combinations of perfusion parameters, lesion volume, and neurological assessment. However, on top of the brain perfusion, there are other multiple factors that might modify the probability of neuronal apoptosis and necrosis following focal cerebral ischemia. We hypothesize that a diagnostic approach with measurements of selected biochemical parameters in the brain, in addition to those based solely on perfusion or MR diffusion, might allow for more personalized management protocols. Moreover, some local processes in the brain, triggered by acute ischemia or its consequences other than hypoperfusion directly, like, for example, excitotoxicity, might lead to apoptosis of the cells in the brain localized also beyond the area of hypoperfusion. This phenomenon might be responsible for the expansion of the brain damage much beyond the initial perfusion deficit or beyond the initial diffusion (DWI) restriction area, reported for example in T2W or FLAIR MRI in some stroke patients who have no other reasons to deteriorate (a reverse DWI - T2W / FLAIR, a reverse perfusion - DWI, or a reverse DWI - DWI mismatch).

Changes of augmentation index early after ischaemic stroke predict functional outcome.

Purpose: Outcome after ischaemic stroke (AIS) depends on multiple factors, including values of blood pressure (BP) and arterial stiffness (AS) in the early phase. It is also known that stroke outcome is affected by BP variability; however, the influence of AS oscillations in the early phase of stroke on its prognosis is unknown. The aim of our study was to assess the relationship between changes of AS markers and stroke outcome.Materials and methods: Baseline clinical data, BP parameters, and markers of AS (pulse wave velocity [PWV], augmentation index [AIx]) were assessed 1, 6, and >90 days after AIS. The outcomes were defined using modified Rankin scale (mRS) score: early favourable (EFO) and early poor (EPO), as mRS ≤1 and >2 points at discharge, respectively; late favourable (LFO) and late poor (LPO), as mRS ≤1 and >2 points on day >90, respectively.Results: In the recruited 50 patients (62.2 ± 12.1 years, 68% males), BP and PWV decreased while AIx did not change within 90 days after AIS. Twenty-eight patients (56%) had EFO, 10 (20%) - EPO, 29 (58%) - LFO, and 9 (18%) - LPO. In univariate analysis, rise in AIx in days 1-6 was associated with EFO (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.02-1.17, p = 0.01) and LFO (OR = 1.08; 95%CI = 1.01-1.14, p = 0.02), whereas decrease in AIx in days 1-6 was associated with EPO (OR = 1.07, 95%CI = 1.00-1.15, p = 0.05). For EFO and LFO, the relationships remained significant after including confounders (p = 0.03 and p = 0.03, respectively).Conclusions: Rise in AIx within one week after ischaemic stroke may be of additional importance in determining better early and late favourable functional outcome.

Genetic and Clinical Heterogeneity in Thirteen New Cases with Aceruloplasminemia. Atypical Anemia as a Clue for an Early Diagnosis.

Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmin (CP) gene that produce a strong reduction or absence of ceruloplasmin ferroxidase activity, leading to an impairment of iron metabolism. Most patients described so far are from Japan. Prompt diagnosis and therapy are crucial to prevent neurological complications since, once established, they are usually irreversible. Here, we describe the largest series of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene (7 missense, 3 frameshifts, and 3 splicing mutations), 10 of which are novel. All missense mutations were studied by computational modeling. Clinical manifestations were heterogeneous, but anemia, often but not necessarily microcytic, was frequently the earliest one. This study confirms the clinical and genetic heterogeneity of aceruloplasminemia, a disease expected to be increasingly diagnosed in the Next-Generation Sequencing (NGS) era. Unexplained anemia with low transferrin saturation and high ferritin levels without inflammation should prompt the suspicion of aceruloplasminemia, which can be easily confirmed by low serum ceruloplasmin levels. Collaborative joint efforts are needed to better understand the pathophysiology of this potentially disabling disease.

Differences in acute ischaemic stroke care in Poland: analysis of claims database of National Health Fund in 2017.

Selected and basic indicators of acute ischaemic stroke care in Poland are reported cross-regionally based on the analysis of claims data of the National Health Fund (NFZ) in 2017, the most reliable source of healthcare funding in the country, being a single public payer. For research purposes, a selection algorithm based on the diagnosis coded as I63 according to the International Classification of Diseases (ICD-10) was used to identify all ischaemic stroke patients in the claims database provided by the NFZ. Stroke units and other centres providing treatment for acute ischaemic stroke patients were examined. The analysis showed marked differences between provinces in terms of stroke unit treatment availability. The crude and standardised rates of acute ischaemic stroke admissions to stroke units varied between provinces. Moreover, substantial differences were observed for the thrombolysis implementation rate, access to rehabilitation, hospital stay and early prognosis. As the leading cause of disability and the second leading cause of death in developed countries, stroke requires a well-organised, evidence-based healthcare system provided for both acute treatment and rehabilitation. Continuous monitoring of healthcare is crucial to identify weaknesses and areas for improvement.

A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene.

Inherited ataxias are a group of highly heterogeneous, complex neurological disorders representing a significant diagnostic challenge in clinical practice. We performed a next-generation sequencing (NGS) analysis in 10 index cases with unexplained progressive cerebellar ataxia of suspected autosomal recessive inheritance. A definite molecular diagnosis was obtained in 5/10 families and included the following diseases: autosomal recessive spastic ataxia of Charlevoix-Saguenay, POLR3B-related hypomyelinating leukodystrophy, primary coenzyme Q10 deficiency type 4, Niemann-Pick disease type C1 and SYNE1-related ataxia. In addition, we found a novel homozygous MTCL1 loss of function variant p.(Lys407fs) in a 23-year-old patient with slowly progressive cerebellar ataxia, mild intellectual disability, seizures in childhood and episodic pain in the lower limbs. The identified variant is predicted to truncate the protein after first 444 of 1586 amino acids. MTCL1 encodes a microtubule-associated protein highly expressed in cerebellar Purkinje cells; its knockout in a mouse model causes ataxia. We propose MTCL1 as a candidate gene for autosomal recessive cerebellar ataxia in humans. In addition, our study confirms the high diagnostic yield of NGS in early-onset cerebellar ataxias, with at least 50% detection rate in our ataxia cohort.

Treatment of acute basilar artery occlusion: Systematic review and meta-analysis.

INTRODUCTION: Acute basilar artery occlusion (BAO) results in strokes characterized by poor outcome. Intravenous and intraarterial thrombolysis with rt-PA (IV rt-PA and IA rt-PA, respectively) and mechanical thrombectomy (MT) are the most commonly used techniques to treat BAO, but their efficacy remains unclear. Unlike in previous papers, we compared all three methods of the treatment in a single work, including an update of meta-analysis regarding each of the three therapeutic approaches with recent trials. METHODS: We systematically reviewed all original studies testing the efficacy of any of the three basic methods of BAO treatment dated up to the end of Jan 2017. RESULTS: The final analysis included 31 studies that summarized 1358 patients. These subjects were organized into three therapeutic groups: IV rt-PA, IA rt-PA±IV rt-PA, MT±IV rt-PA±IA rt-PA. The weighted pooled estimates of a favorable outcome (mRS 0-2) were 32.57% (95% CI 16.44-51.03%/I2=67.5%, p=0.0795) in the first group, 22.56% (95% CI 16.85-28.79%/I2=52.1%, p=0.027) in the second group, and 37.04% (95% CI 32.27-41.92%/I2=32%, p=0.0895) in the third group. The Q-test subgroup analysis revealed the statistical superiority of MT±IV rt-PA±IA rt-PA over IA rt-PA±IV rt-PA (mRS 0-2: p=0.0003, mRS 6: p=0.0010) and over any rt-PA administration (either IV rt-PA or IA rt-PA±IV rt-PA) (mRS 0-2: p=0.0006, mRS 6: p=0.0056). CONCLUSIONS: Current data on the effects of the three basic approaches of the treatment of BAO are insufficient to generate high-class EBM guidelines. MT seems to be the most effective method of the treatment of acute BAO. The efficacy of IV or IA thrombolytic therapy in this indication remains unclear.

What causes intracerebral bleeding after thrombolysis for acute ischaemic stroke? Recent insights into mechanisms and potential biomarkers.

The overall population benefit of intravascular recombinant tissue plasminogen activator (rtPA) on functional outcome in ischaemic stroke is clear, but there are some treated patients who are harmed by early symptomatic intracranial haemorrhage (ICH). Although several clinical and radiological factors increase the risk of rtPA-related ICH, none of the currently available risk prediction tools are yet useful for practical clinical decision-making, probably reflecting our limited understanding of the underlying mechanisms. Finding new methods to identify patients at highest risk of rtPA-related ICH, or new measures to limit risk, are urgent challenges in acute stroke therapy research. In this article, we focus on the potential underlying mechanisms of rtPA-related ICH, highlight promising candidate risk biomarkers and suggest future research directions.

Circulating miRNA profiles and the risk of hemorrhagic transformation after thrombolytic treatment of acute ischemic stroke: a pilot study.

Background: Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown. Objective: This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not. Methods: Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with p < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only. Results: We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium. Conclusion: miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works.

The proton-sensing receptors TDAG8 and GPR4 are differentially expressed in human and mouse oligodendrocytes: Exploring their role in neuroinflammation and multiple sclerosis.

Acidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). The response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4 and TDAG8. These receptors are inactive at alkaline pH, reaching maximal activation at acidic pH. Genome-wide association studies have identified a locus within the TDAG8 gene associated with several autoimmune diseases, including MS. Accordingly, we here found that expression of TDAG8, as opposed to GPR4 or OGR1, is upregulated in MS plaques. This led us to investigate the expression of TDAG8 in oligodendrocytes using mouse and human in vitro and in vivo models. We observed significant upregulation of TDAG8 in human MO3.13 oligodendrocytes during maturation and in response to acidic conditions. However, its deficiency did not impact normal myelination in the mouse CNS, and its expression remained unaltered under demyelinating conditions in mouse organotypic cerebellar slices. Notably, our data revealed no expression of TDAG8 in primary mouse oligodendrocyte progenitor cells (OPCs), in contrast to its expression in primary human OPCs. Our investigations have revealed substantial species differences in the expression of proton-sensing receptors in oligodendrocytes, highlighting the limitations of the employed experimental models in fully elucidating the role of TDAG8 in myelination and oligodendrocyte biology. Consequently, the study does not furnish robust evidence for the role of TDAG8 in such processes. Nonetheless, our findings tentatively point towards a potential association between TDAG8 and myelination processes in humans, hinting at a potential link between TDAG8 and the pathophysiology of MS and warrants further research.

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.

Baseline characteristics, reperfusion treatment secondary prevention and outcome after acute ischemic stroke in three different socioeconomic environments in Europe.

INTRODUCTION: The differences in vascular risk factors' and stroke burden across Europe are notable, however there is limited understanding of the influence of socioeconomic environment on the quality of secondary prevention and outcome after acute ischemic stroke. PATIENTS AND METHODS: In this observational multicenter cohort study, we analyzed baseline characteristics, reperfusion treatment, outcome and secondary prevention in patients with acute ischemic stroke from three tertiary-care teaching hospitals with similar service population size in different socioeconomic environments: Bern/CH/n = 293 (high-income), Gdansk/PL/n = 140 (high-income), and Lutsk/UA/n = 188 (lower-middle-income). RESULTS: We analyzed 621 patients (43.2% women, median age = 71.4 years), admitted between 07 and 12/2019. Significant differences were observed in median BMI (CH = 26/PL = 27.7/UA = 27.8), stroke severity [(median NIHSS CH = 4(0-40)/PL = 11(0-33)/UA = 7(1-30)], initial neuroimaging (CT:CH = 21.6%/PL = 50.7%/UA = 71.3%), conservative treatment (CH = 34.1%/PL = 38.6%/UA = 95.2%) (each p < 0.001), in arterial hypertension (CH = 63.8%/PL = 72.6%/UA = 87.2%), atrial fibrillation (CH = 28.3%/PL = 41.4%/UA = 39.4%), hyperlipidemia (CH = 84.9%/PL = 76.4%/UA = 17%) (each p < 0.001) and active smoking (CH = 32.2%/PL = 27.3%/UA = 10.2%) (p < 0.007). Three-months favorable outcome (mRS = 0-2) was seen in CH = 63.1%/PL = 50%/UA = 59% (unadjusted-p = 0.01/adjusted-p CH-PL/CH-UA = 0.601/0.981), excellent outcome (mRS = 0-1) in CH = 48.5%/PL = 32.1%/UA = 27% (unadjusted-p < 0.001/adjusted-p CH-PL/CH-UA = 0.201/0.08 and adjusted-OR CH-UA = 2.09). Three-months mortality was similar between groups (CH = 17.2%/PL = 15.7%/UA = 4.8%) (unadjusted-p = 0.71/adjusted-p CH-PL/CH-UA = 0.087/0.24). Three-months recurrent stroke/TIA occurred in CH = 3.1%/PL = 10.7%/UA = 3.1%, adjusted-p/OR CH-PL = 0.04/0.32). Three-months follow-up medication intake rates were the same for antihypertensives. Statin/OAC intake was lowest in UA = 67.1%/25.5% (CH = 87.3%/39.2%/unadjusted-p < 0.001/adjusted-p CH-UA = 0.02/0.012/adjusted-OR CH-UA = 2.33/2.18). Oral intake of antidiabetics was lowest in CH = 10.8% (PL = 15.7%/UA = 16.1%/unadjusted-p = 0.245/adjusted-p CH-PL/CH-UA = 0.061/0.002/adjusted-OR CH-UA = 0.25). Smoking rates decreased in all groups during follow-up. DISCUSSION AND CONCLUSION: Substantial differences in presentation, treatment and secondary prevention measures, are linked to a twofold difference in adjusted 3-months excellent outcome between Switzerland and Ukraine. This underscores the importance of socioeconomic factors that influence stroke outcomes, emphasizing the necessity for targeted interventions to address disparities in treatment and secondary prevention strategies.

Apparent diffusion coefficient thresholds and diffusion lesion volume in acute stroke.

BACKGROUND: Apparent diffusion coefficient (ADC) thresholds are used to determine acute stroke lesion volume, but the reliability of this approach and comparability to the volume of the magnetic resonance diffusion-weighted imaging (MR-DWI) hyperintense lesion is unclear. METHODS: We prospectively recruited and clinically assessed patients who had experienced acute ischemic stroke and performed DWI less than 24 hours and at 3 to 7 days after stroke. We compared the volume of the manually outlined DW hyperintense lesion (reference standard) with lesion volumes derived from 3 commonly used ADC thresholds: .55 × 10(-3)/mm(2)/second(-1), .65 × 10(-3)/mm(2)/second(-1), and .75 × 10(-3)/mm(2)/second(-1), with and without "editing" of erroneous tissue. We compared the volumes obtained by reference standard, "raw," and "edited" thresholds. RESULTS: Among 33 representative patients, the acute DWI lesion volume was 15,284 mm(3); the median unedited/edited ADC volumes were 52,972/2786 mm(3), 92,707/6,987 mm(3), and 227,681/unmeasureable mm(3) (.55 × 10(-3)/mm(2)/second(-1), .65 × 10(-3)/mm(2)/second(-1), and .75 × 10(-3)/mm(2)/second(-1) thresholds, respectively). Subacute lesions gave similar differences. These differences between edited and unedited diffusion-weighted imaging and ADC volumes were statistically significant. CONCLUSIONS: Threshold-derived ADC volumes require substantial manual editing to avoid over- or underestimating the visible DWI lesion and should be used with caution.