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

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

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

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

The benefit of optimizing recanalization during mechanical thrombectomy in patients with acute ischemic stroke depends on preprocedural tissue-level collateralization.

PURPOSE: Thrombolysis in Cerebral Infarction (TICI) 3 represents the optimal angiographic outcome following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Although it is known to yield better outcomes than TICI 2b, the influence of preprocedural cerebral hemodynamics on the clinical advantage of TICI 3 over TICI 2b remains unexplored. METHODS: This single-center retrospective analysis involved patients with anterior circulation AIS who underwent successful recanalization during MT at the Comprehensive Stroke Center, University Hospital, Krakow between January 2019 and July 2023. We assessed the benefit of achieving TICI 2c/3 over TICI 2b on the basis of preprocedural computed perfusion imaging results, primarily focusing on early infarct volume (EIV) and tissue-level collaterals indicated by hypoperfusion intensity ratio (HIR). Good functional outcome (GFO) was defined as a modified Rankin Score < 3 on day 90. RESULTS: The study comprised 612 patients, of whom 467 (76.3%) achieved TICI 2c/3. GFO was more frequent in the TICI 2c/3 group (54.5% vs 69.4%, p < 0.001). There was interaction between the recanalization status and both HIR (Pi = 0.042) and EIV (Pi = 0.012) in predicting GFO, with disproportionately higher impact of HIR and EIV in TICI 2b group. The benefit from TICI 2c/3 over TICI 2b was insignificant among patients with good collaterals, defined by HIR < 0.3 (odds ratio:1.36 [0.58-3.18], p = 0.483). CONCLUSION: TICI 2c/3 improves patient functional outcomes compared to TICI 2b regardless of EIV. However, such angiographic improvement may be clinically futile in patients with good tissue-level collateralization. Our findings suggest that preprocedural HIR should be considered when optimization of recanalization is considered during MT.

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

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

Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer's Disease.

Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer's disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with (n = 42) AD, (n = 18) mild cognitive impairment (MCI) and (n = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinflammatory proteins, NGAL, and CXCL-11 reached a peak in the early stage of the disease and allowed for the identification of patients with MCI. Furthermore, the concentration of the anti-inflammatory molecule sTREM2 was highest in the more advanced stage of the disease and permitted differentiation between AD and non-demented controls. Additionally, sTREM2 was biochemically linked to tau and pTau in the AD group. Notably, NGAL demonstrated superior diagnostic performance compared to classical AD biomarkers in discriminating MCI patients from controls. These findings suggest that proteins secreted mainly through microglia dysfunction might play not only a detrimental but also a protective role in the development of AD pathology.

Evaluating the interaction between hemorrhagic transformation and cerebral edema on functional outcome after ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation. METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately. RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001]. CONCLUSIONS: Most stroke patients with HT also have measurable CED. The co-occurrence of CED and HT occurs in larger and more severe strokes and is associated with worse functional outcome, although this is driven by greater severity of stroke-related edema in those with HT.

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

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

Mechanical thrombectomy in very elderly people: shortand long-term outcomes of endovascular stroke treatment in nonagenarians.

AIM OF STUDY: To assess outcomes of mechanical thrombectomy (MT) in nonagenarians suffering from acute ischaemic stroke (AIS) in a 1-year follow-up. CLINICAL RATIONALE FOR STUDY: Age is a factor associated with both the occurrence of AIS and a poorer prognosis. As the population ages, the prevalence of AIS among the very old (90 and older) is expected to rise. Data on long-term outcomes of MT, being the optimal treatment of AIS caused by large vessel occlusions, is scarce in the population of nonagenarians. MATERIAL AND METHODS: We analysed all AIS patients treated with MT in a single Comprehensive Stroke Centre. We compared two subgroups: nonagenarians (people aged 90-99) and controls ( < 90 years) in terms of cardiovascular risk factors profile, stroke severity, treatment course, presence of in-hospital complications, and outcomes (mortality and good functional outcome defined as modified Rankin Scale ≤ 2) at discharge and at 90- and 365-day follow-ups. RESULTS: Nonagenarians were more commonly female and suffering from atrial fibrillation. They more often developed urinary tract infection during hospitalisation. Stroke severity, treatment course and in-hospital outcomes were comparable between the groups. Nonagenarians had non-significantly higher 90-day and 365-day mortality, and a significantly lower rate of good functional outcomes after 90 days (25.0% vs 57.7%, p = 0.011) and 365 days (31.5% vs 61.0%, p = 0.020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Despite worse outcomes than in younger patients, 25% of nonagenarians were functionally independent three months after MT, and almost one in three of them were so a year after the procedure, thereby showing the benefits of the treatment in this group.

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

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

The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Genetic Architecture of Stroke of Undetermined Source: Overlap with Known Stroke Etiologies and Associations with Modifiable Risk Factors.

OBJECTIVE: Ischemic stroke etiology remains undetermined in 30% of cases. We explored the genetic architecture of stroke classified as undetermined to test if mechanisms and risk factors underlying large-artery atherosclerotic (LAAS), cardioembolic (CES), and small-vessel stroke (SVS) contribute to its pathogenesis. METHODS: We analyzed genome-wide data from 16,851 ischemic stroke cases and 32,473 controls. Using polygenic risk scores for LAAS, CES, and SVS, we assessed the genetic overlap with stroke of undetermined source and used pairwise genomewide association study (GWAS-PW) to search for shared loci. We then applied Mendelian randomization (MR) to identify potentially causal risk factors of stroke of undetermined source. RESULTS: Genetic risk for LAS, CES, and SVS was associated with stroke of undetermined source pointing to overlap in their genetic architecture. Pairwise analyses revealed 19 shared loci with LAAS, 2 with CES, and 5 with SVS that have been implicated in atherosclerosis-related phenotypes. Genetic liability to both carotid atherosclerosis and atrial fibrillation was associated with stroke of undetermined source, but the association with atrial fibrillation was attenuated after excluding cases with incomplete diagnostic workup. MR analyses showed effects of genetically determinants of blood pressure, diabetes, waist-to-hip ratio, inflammatory pathways (IL-6 signaling, MCP-1/CCL2 levels), and factor XI levels on stroke of undetermined source. INTERPRETATION: Stroke of undetermined source shares genetic and vascular risk factors with other stroke subtypes, especially LAAS, thus highlighting the diagnostic limitations of current subtyping approaches. The potentially causal associations with carotid atherosclerosis and atherosclerotic risk factors might have implications for prevention strategies targeting these mechanisms. ANN NEUROL 2022;91:640-651.

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

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

Trends in antiseizure medications utilization among women of childbearing age with epilepsy in Poland between 2015 and 2019.

PURPOSE: To determine trends in the use of antiseizure medications (ASMs) among women of childbearing age (WOCA) and girls aged 12-14 years with epilepsy between 2015 and 2019 in Poland. METHODS: The study used data from the Pex database, which captures information on prescriptions dispensed from 85% of community pharmacies in Poland. The prescriptions issued by neurologists who provide epilepsy care in Poland were studied. Six of the most commonly prescribed ASMs were analyzed: carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, topiramate, and valproate. RESULTS: The use of valproate and carbamazepine decreased in all age groups. Among the newer ASMs, the use of lamotrigine, levetiracetam, and topiramate increased and oxcarbazepine decreased significantly in WOCA. The only subgroup with statistically significant changes in all ASMs prescriptions were women aged 19-34 years. For girls aged 12-14 years, significant changes were found only for valproate and carbamazepine. In the last year of observation (2019) valproate and lamotrigine accounted for two-thirds of ASMs units prescribed to WOCA. Valproate accounted for half of the prescribed drug units in girls aged 12-14 years. The lowest rates of VPA prescriptions were found in women aged 19-34 years. CONCLUSIONS: There is a change in prescribing habits in WOCA with epilepsy in Poland with trends toward using less teratogenic ASMs. However, many WOCAs are treated with valproate and topiramate despite their known teratogenicity risk. Valproate is still the most commonly prescribed ASM in WOCA and girls aged 12-14 years. Educational interventions for healthcare professionals are needed to improve prescribing practices in WOCA with epilepsy in Poland.

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

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

Factors affecting self-reported bleeding acceptance in acute ischemic stroke survivors on various types of antithrombotic therapy.

OBJECTIVES: Prior ischemic cerebrovascular event and younger age have been shown to increase bleeding acceptance among anticoagulated outpatients with atrial fibrillation (AF). We sought to determine factors affecting bleeding acceptance in acute ischemic stroke (AIS) survivors on various types of antithrombotic therapy. MATERIALS AND METHODS: We enrolled 173 consecutive patients hospitalized for AIS (aged 68.2±11.7 years, 54.9% male), including 54 (31.2%) with AF, who had favorable functional outcome. On discharge, the Bleeding ratio, defined as the declared maximum number of major bleedings that a patient is willing to accept to prevent one major stroke, was evaluated. We assessed the predicted bleeding risk in non-cardioembolic and cardioembolic stroke survivors using S2TOP-BLEED and HAS-BLED scores, respectively. RESULTS: Patients with the low Bleeding ratio, defined as 5 (median) or less accepted bleeds (n=92; 53.2%), were older and more likely to receive thrombolysis and/or thrombectomy, with no impact of previous stroke. Prior major bleed (odds ratio [OR] 4.67; 95% confidence interval [CI] 0.92-23.72), AF with use of oral anticoagulants (OR 2.35, 95% CI 1.12-4.93), reperfusion treatment (OR 1.95, 95% CI 1.02-3.76), and hospitalization ≤10 days (OR 4.56; 95% CI 1.50-13.87) were associated with the low Bleeding Ratio. Prior use of anticoagulants or aspirin as well as HAS-BLED and S2TOP-BLEED scores did not affect the bleeding acceptance. CONCLUSIONS: Lower bleeding acceptance declared on discharge by AIS survivors is determined by prior bleeding, anticoagulation in AF, reperfusion treatment, and duration of hospitalization, which might affect medication adherence. The results might help optimize post-discharge management and educational efforts in patients on antithrombotic therapy.

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

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

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

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

High prevalence of electroencephalographic frontal intermittent rhythmic delta activity in patients with moderately severe COVID-19.

INTRODUCTION: The aim of our study was to analyse EEG findings in patients with COVID-19 not requiring respiratory support. MATERIAL AND METHODS: We reviewed EEGs performed in patients with COVID-19 between April 2020 and May 2021 at the University Hospital in Kraków, Poland. Demographic and clinical data, including comorbid conditions, discharge disposition, survival, neuroimaging findings, laboratory results, and treatment was collected. RESULTS: The study included 44 EEGs performed in 35 patients (51.4% females), aged 65.5 ± 13.9 years. Almost all patients had at least one comorbidity, and one-third had one or more preexisting neurological conditions. Three quarters of EEGs were abnormal. The most frequent EEG finding was background slowing (16 patients; 45.7%). Frontal findings included frontally predominant rhythmic delta (FIRDA) in 10 (28.6%) patients and focal slowing in the left frontal lobe. Patients with abnormal EEG significantly more often required oxygen supplementation (p = 0.003) and were less likely to recover (p = 0.048). CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with COVID-19 infection may frequently manifest with an abnormal EEG. FIRDA seems to be a frequent EEG pattern in less severe cases of COVID-19 infection. Future studies are needed to establish whether COVID-19 infection increases the risk for FIRDA, and to investigate its pathogenesis.

Course of fatigue among patients previously hospitalised due to COVID-19.

INTRODUCTION: Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection. MATERIAL AND METHODS: Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0-4 weeks, 4-12 weeks, and > 12 weeks post-infection. RESULTS: We enrolled 204 patients [40.2% women, median age 58 (46-66) years] evaluated after a median of 187 (156-220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4-12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [ß 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0-12 and > 12, respectively], and age [for < 4 weeks, ß -0.12 (-0.28; -0.01), p = 0.029]. CONCLUSIONS: Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and - only for the acute phase - age.

Sex-related patient-reported brain fog symptoms in non-hospitalised COVID-19 patients.

INTRODUCTION: Previous studies on the prognostic role of sex in post-COVID-associated brain fog have yielded divergent results. Moreover, limited evidence exists regarding the evolution of brain fog symptoms over time, especially in ambulatory patients and separately for women and men. Therefore, the aim of the current study was to assess brain fog symptoms in nonhospitalised patients with COVID-19, according to their sex. MATERIAL AND METHODS: We created a neuropsychological questionnaire including eight questions on the presence of brain fog symptoms in the following four time periods: before COVID-19, and 0-4, 4-12, and > 12 weeks post-infection. The validity and reliability of the questionnaire were assessed. In this cross-sectional study, questionnaires were filled out anonymously and retrospectively once only by patients or through a survey link posted online. Included were patients ≥ 18 years, with > 3 months since the SARS-CoV-2 infection onset confirmed by RT-PCR from a nasopharyngeal swab. RESULTS: The study included 303 patients (79.53% women, 47.52% medical personnel). Median time between COVID-19 onset and questionnaire completion was 208 (IQR 161-248) days. Women, compared to men, reported a higher prevalence of problems with writing, reading, and counting (< 4 weeks, OR 3.05, 95% CI: 1.38-6.72; 4-12 weeks, OR 2.51, 95% CI: 1.02-6.14; > 12 weeks, OR 3.74, 95% CI: 1.12-12.56) and thoughts communication (< 4 weeks, OR 2.53, 95% CI: 1.41-4.54; 4-12 weeks, OR 3.74, 95% CI: 1.93-7.24; > 12 weeks, OR 2.00, 95% CI: 1.01-3.99). The difference between the two sexes in answering questions in an understandable/unambiguous manner was statistically significant between four and 12 weeks after infection (OR 2.63, 95% CI: 1.36-5.10), while a sex difference in recalling new information was found below 12 weeks (OR 2.54, 95% CI: 1.44-4.48 and OR 2.43, 95% CI: 1.37-4.31 for < 4 and 4-12 weeks, respectively). No sex differences in reporting problems with multitasking, remembering information from the past, determining the current date, or field orientation were noted. CONCLUSIONS: Non-hospitalised women and men retrospectively report a different course of COVID-19-associated brain fog.