Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. METHODS: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. RESULTS: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). CONCLUSION: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study.

BACKGROUND: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO. METHODS: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts. RESULTS: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15). CONCLUSION: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.

Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke.

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Augenblickdiagnose in neurology: Revisiting 'diagnosis in the blink of an eye'.

BACKGROUND AND PURPOSE: The art of diagnosis in clinical neurology requires attentive listening and careful observation. In certain situations, a fragment of the history or a physical sign may be so distinctive that it allows clinicians to evoke a specific diagnosis. This quick mental process was previously referred to as 'Augenblickdiagnose' ('diagnosis in the blink of an eye') in a seminal paper by Dr. William Campbell in 1998. We aimed to revisit this concept by providing additional clinical vignettes. METHODS: The authors wrote clinical vignettes using examples from their own clinical practice and performed a non-systematic review of influential neurology textbooks using the words 'pathognomonic' and 'highly suggestive'. RESULTS: Twenty examples from various fields of neurology are presented in a table, stratified by major fields of neurology. A short educational reflection is provided for each diagnosis considered. CONCLUSION: 'Augenblickdiagnose' is an engaging teaching resource that also contributes to 'neurophilia', that is, a fascination for neurology, perhaps increasingly in today's modern neurology practice. However, multiple cognitive biases underlying mental shortcuts may lead to an incorrect diagnosis. It is important to stress that good clinical practice in neurology requires taking a thorough history and performing a careful neurological examination.

Iron age genomic data from Althiburos - Tunisia renew the debate on the origins of African taurine cattle.

The Maghreb is a key region for understanding the dynamics of cattle dispersal and admixture with local aurochs following their earliest domestication in the Fertile Crescent more than 10,000 years ago. Here, we present data on autosomal genomes and mitogenomes obtained for four archaeological specimens of Iron Age (∼2,800 cal BP-2,000 cal BP) domestic cattle from the Eastern Maghreb, i.e. Althiburos (El Kef, Tunisia). D-loop sequences were obtained for an additional eight cattle specimens from this site. Maternal lineages were assigned to the elusive R and ubiquitous African-T1 haplogroups found in two and ten Althiburos specimens, respectively. Our results can be explained by post-domestication hybridization of Althiburos cattle with local aurochs. However, we cannot rule out an independent domestication in North Africa considering the shared ancestry of Althiburos cattle with the pre-domestic Moroccan aurochs and present-day African taurine cattle.

Northwest African Neolithic initiated by migrants from Iberia and Levant.

In northwestern Africa, lifestyle transitioned from foraging to food production around 7,400 years ago but what sparked that change remains unclear. Archaeological data support conflicting views: (1) that migrant European Neolithic farmers brought the new way of life to North Africa1-3 or (2) that local hunter-gatherers adopted technological innovations4,5. The latter view is also supported by archaeogenetic data6. Here we fill key chronological and archaeogenetic gaps for the Maghreb, from Epipalaeolithic to Middle Neolithic, by sequencing the genomes of nine individuals (to between 45.8- and 0.2-fold genome coverage). Notably, we trace 8,000 years of population continuity and isolation from the Upper Palaeolithic, via the Epipaleolithic, to some Maghrebi Neolithic farming groups. However, remains from the earliest Neolithic contexts showed mostly European Neolithic ancestry. We suggest that farming was introduced by European migrants and was then rapidly adopted by local groups. During the Middle Neolithic a new ancestry from the Levant appears in the Maghreb, coinciding with the arrival of pastoralism in the region, and all three ancestries blend together during the Late Neolithic. Our results show ancestry shifts in the Neolithization of northwestern Africa that probably mirrored a heterogeneous economic and cultural landscape, in a more multifaceted process than observed in other regions.

Imputed genomes and haplotype-based analyses of the Picts of early medieval Scotland reveal fine-scale relatedness between Iron Age, early medieval and the modern people of the UK.

There are longstanding questions about the origins and ancestry of the Picts of early medieval Scotland (ca. 300-900 CE), prompted in part by exotic medieval origin myths, their enigmatic symbols and inscriptions, and the meagre textual evidence. The Picts, first mentioned in the late 3rd century CE resisted the Romans and went on to form a powerful kingdom that ruled over a large territory in northern Britain. In the 9th and 10th centuries Gaelic language, culture and identity became dominant, transforming the Pictish realm into Alba, the precursor to the medieval kingdom of Scotland. To date, no comprehensive analysis of Pictish genomes has been published, and questions about their biological relationships to other cultural groups living in Britain remain unanswered. Here we present two high-quality Pictish genomes (2.4 and 16.5X coverage) from central and northern Scotland dated from the 5th-7th century which we impute and co-analyse with >8,300 previously published ancient and modern genomes. Using allele frequency and haplotype-based approaches, we can firmly place the genomes within the Iron Age gene pool in Britain and demonstrate regional biological affinity. We also demonstrate the presence of population structure within Pictish groups, with Orcadian Picts being genetically distinct from their mainland contemporaries. When investigating Identity-By-Descent (IBD) with present-day genomes, we observe broad affinities between the mainland Pictish genomes and the present-day people living in western Scotland, Wales, Northern Ireland and Northumbria, but less with the rest of England, the Orkney islands and eastern Scotland-where the political centres of Pictland were located. The pre-Viking Age Orcadian Picts evidence a high degree of IBD sharing across modern Scotland, Wales, Northern Ireland, and the Orkney islands, demonstrating substantial genetic continuity in Orkney for the last ~2,000 years. Analysis of mitochondrial DNA diversity at the Pictish cemetery of Lundin Links (n = 7) reveals absence of direct common female ancestors, with implications for broader social organisation. Overall, our study provides novel insights into the genetic affinities and population structure of the Picts and direct relationships between ancient and present-day groups of the UK.

Diagnostic accuracy of CT angiography and CT perfusion imaging for detecting distal medium vessel occlusions: Protocol for a systematic review and meta-analysis.

BACKGROUND: Distal medium vessel occlusions (DMVOs) represent 25-40% of all acute ischemic strokes (AIS). DMVO clinical syndromes are heterogenous, but as eloquent brain regions are frequently involved, they are often disabling. Since current intravenous fibrinolytic therapies may fail to recanalize up to two-thirds of DMVOs, endovascular treatment is progressively being considered in this setting. Nevertheless, the optimal imaging method for diagnosis remains to be defined. Stroke centers that use computed tomography as a routine stroke imaging approach rely on either isolated computed tomography angiography (CTA) or combined perfusion (CTP) studies. Despite a simplified non-CTP-dependent approach seeming reasonable for large vessel occlusion AIS diagnosis, CTP may still hold advantages for DMVOs workup. Therefore, this systematic review aims to compare the diagnostic performance of CTA and CTP in detecting DMVOs. METHODS: We will perform a systematic search in PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include any type of study that presents data on the diagnostic accuracy of CTA and/or CTP for detecting DMVOs. Two authors will independently review retrieved studies, and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. Data will be combined in a quantitative meta-analysis following the guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: This will be the first systematic review and meta-analysis that compares two different imaging approaches for detecting DMVOs. This study may help to define optimal acute ischemic stroke imaging work-up. TRIAL REGISTRATION: PROSPERO registration: CRD42022344006.

Predictors of cognitive dysfunction one-year post COVID-19.

OBJECTIVES: (a) To characterize the frequency of objective cognitive deficits and self-perceived cognitive difficulties and (b) to explore demographic and clinical predictors of cognitive dysfunction and cognitive complaints. METHOD: One hundred and ten adults diagnosed with COVID-19 between March and November 2020, aged ≤ 74 years underwent a brief neuropsychological evaluation 12 months after infection, which included: Brief Visuospatial Memory Test-Revised, California Verbal Learning Test, and Symbol Digit Modalities Test. T scores < 38 were considered abnormal performance; cognitive dysfunction was defined as ≥ 2 abnormal tests. Participants also completed Broadbent's Cognitive Failure Questionnaires (CFQ), Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, and Short-Form Health Survey. CFQ ≥ 43 was considered indicative of cognitive complaints. RESULTS: Twenty participants (18.2%) had cognitive dysfunction and 36 (33.3%) had cognitive complaints. Cognitive dysfunction was related to lower education, preinfection history of headache/migraine, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were more likely to occur in women, those with fewer years of education, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were also significantly related to symptoms of anxiety, depression, and fatigue. Sex and psychopathology were not significant predictors of cognitive dysfunction. Modest associations were found between CFQ total score and cognitive test performance. DISCUSSION: A subset of individuals develops cognitive difficulties in the context of post-COVID syndrome. Results may support the protective effect of education, a known proxy of cognitive reserve. COVID-19 infection symptoms of headache and sleep disturbance appear to be risk factors for long-term cognitive difficulties. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The genetic history of Scandinavia from the Roman Iron Age to the present.

We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.

Spatial and temporal heterogeneity in human mobility patterns in Holocene Southwest Asia and the East Mediterranean.

We present a spatiotemporal picture of human genetic diversity in Anatolia, Iran, Levant, South Caucasus, and the Aegean, a broad region that experienced the earliest Neolithic transition and the emergence of complex hierarchical societies. Combining 35 new ancient shotgun genomes with 382 ancient and 23 present-day published genomes, we found that genetic diversity within each region steadily increased through the Holocene. We further observed that the inferred sources of gene flow shifted in time. In the first half of the Holocene, Southwest Asian and the East Mediterranean populations homogenized among themselves. Starting with the Bronze Age, however, regional populations diverged from each other, most likely driven by gene flow from external sources, which we term "the expanding mobility model." Interestingly, this increase in inter-regional divergence can be captured by outgroup-f3-based genetic distances, but not by the commonly used FST statistic, due to the sensitivity of FST, but not outgroup-f3, to within-population diversity. Finally, we report a temporal trend of increasing male bias in admixture events through the Holocene.

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

BACKGROUND AND OBJECTIVES: COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19. METHODS: This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). RESULTS: Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60). DISCUSSION: Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis. TRIAL REGISTRATION INFORMATION: The study was registered under ClinicalTrials.gov identifier NCT04895462.

CTA and CTP for Detecting Distal Medium Vessel Occlusions: A Systematic Review and Meta-analysis.

BACKGROUND: The optimal imaging method for detecting distal medium vessel occlusions (DMVOs) remains undefined. PURPOSE: The objective of this study is to compare the diagnostic performance of CTA with CTP in detecting DMVOs. DATA SOURCES: We searched PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials up to March 31, 2023 (PROSPERO: CRD42022344006). STUDY SELECTION: A total of 12 studies reporting accuracy values of CTA and/or CTP were included, comprising 2607 patients with 479 cases (18.3%) of DMVOs. DATA ANALYSIS: Pooled sensitivity and specificity of both imaging methods were compared using a random-effects model. Subgroup analyses were performed based on the technique used in CTA (multi or single-phase) and the subtype of DMVOs (M2-only vs. M2 and other DMVOs). We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria. DATA SYNTHESIS: CTA demonstrated significantly lower sensitivity compared to CTP in detecting DMVOs [0.74, 95%CI (0.63-0.82) vs. 0.89, 95% CI (0.82-0.93), P < 0.01]. When subgrouped into single-phase and multi-phase CTA, multi-phase CTA exhibited higher sensitivity for DMVO detection than single-phase CTA [0.91, 95%CI (0.85-0.94) vs. 0.64, 95%CI (0.56-0.71), P < .01], while reaching similar levels to CTP. The sensitivity of single-phase CTA substantially decreased when extending from M2 to other non-M2 DMVOs [0.74, 95%CI (0.63-0.83) vs. 0.61, 0.95%CI (0.53-0.68), P = .02]. LIMITATIONS: We identified an overall high risk of bias and low quality of evidence, attributable to the design and reference standards of most studies. CONCLUSIONS: Our findings highlight a significantly lower sensitivity of single-phase CTA compared to multi-phase CTA and CTP in diagnosing DMVOs.

Early plasma biomarker dynamic profiles are associated with acute ischemic stroke outcomes.

BACKGROUND: Early outcome prediction after acute ischemic stroke (AIS) might be improved with blood-based biomarkers. We investigated whether the longitudinal profile of a multi-marker panel could predict the outcome of successfully recanalized AIS patients. METHODS: We used ultrasensitive single-molecule array (Simoa) to measure glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), total-tau (t-tau) and ELISA for brevican in a prospective study of AIS patients with anterior circulation large vessel occlusion successfully submitted to thrombectomy. Plasma was obtained at admission, upon treatment, 24 h and 72 h after treatment. Clinical and neuroimaging outcomes were assessed independently. RESULTS: Thirty-five patients (64.8%) had good early clinical or neuroimaging outcome. Baseline biomarker levels did not distinguish between outcomes. However, longitudinal intra-individual biomarker changes followed different dynamic profiles with time and according to outcome. GFAP levels exhibited an early and prominent increase between admission and just after treatment. NfL increase was less pronounced between admission and up to 24 h. T-tau increased between treatment and 24 h. Interestingly, GFAP rate-of-change (pg/ml/h) between admission and immediately after recanalization had a good discriminative capacity between clinical outcomes (AUC = 0.88, p < 0.001), which was higher than admission CT-ASPECTS (AUC = 0.75, p < 0.01). T-tau rate-of-change provided moderate discriminative capacity (AUC = 0.71, p < 0.05). Moreover, in AIS patients with admission CT-ASPECTS <9 both GFAP and NfL rate-of-change were good outcome predictors (AUC = 0.82 and 0.77, p < 0.05). CONCLUSION: Early GFAP, t-tau and NfL rate-of-change in plasma can predict AIS clinical and neuroimaging outcome after successful recanalization. Such dynamic measures match and anticipate neuroimaging predictive capacity, potentially improving AIS patient stratification for treatment, and targeting individualized stroke care.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.

Phospholipase A2 and Ischemic Stroke Etiology.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), which is involved in the inflammatory atherosclerotic process, has emerged as an independent risk factor for atheromatous vascular events. Its impact on coronary disease has already been demonstrated, however, its influence in cerebrovascular etiology is still unknown. We aimed to observe and describe the potential association between Lp-PLA2 levels and the etiologic subtype of ischemic stroke. METHODS: Unicentric, observational, and prospective cohort study of consecutive patients with acute ischemic stroke, admitted in a comprehensive stroke center. Patients with incomplete investigation or coexisting causes were excluded. Lp-PLA2 was dosed in peripheral blood between day 3 and 14 postevent with "Lp-PLA2-SNIBE" kit. Statistical significance was set for P<0.05. RESULTS: A total of 96 patients were enrolled, with mean age of 75.31±11.88 years, 41 males (42.7%); 12.5% with lacunar stroke, 16.7% atherothrombotic, 46.9% cardioembolic, and 24% embolic stroke of undetermined source (ESUS). The level of Lp-PLA2 was different between etiologies (F=2.982, P=0.035), being lower in ESUS (143.3±42.8 ng/mL). There were no significant associations with previous vascular risk factors, history of ischemic stroke and modified-Rankin scale (mRS) score 3 months postevent. In ESUS patients, Lp-PLA2 was not associated with cervical ultrasound findings or frequent supraventricular extrasystoles. CONCLUSIONS: Lp-PLA2 levels are different between etiologic subtypes of ischemic stroke, being lower in ESUS patients. The results of this study reinforce the existence of distinct pathophysiological mechanisms in patients with ESUS. Multicenter clinical trials with larger sample sizes are needed to clarify the role Lp-PLA2 on the etiology of stroke.

Human population dynamics and Yersinia pestis in ancient northeast Asia.

We present genome-wide data from 40 individuals dating to c.16,900 to 550 years ago in northeast Asia. We describe hitherto unknown gene flow and admixture events in the region, revealing a complex population history. While populations east of Lake Baikal remained relatively stable from the Mesolithic to the Bronze Age, those from Yakutia and west of Lake Baikal witnessed major population transformations, from the Late Upper Paleolithic to the Neolithic, and during the Bronze Age, respectively. We further locate the Asian ancestors of Paleo-Inuits, using direct genetic evidence. Last, we report the most northeastern ancient occurrence of the plague-related bacterium, Yersinia pestis Our findings indicate the highly connected and dynamic nature of northeast Asia populations throughout the Holocene.

Competitive mapping allows for the identification and exclusion of human DNA contamination in ancient faunal genomic datasets.

BACKGROUND: After over a decade of developments in field collection, laboratory methods and advances in high-throughput sequencing, contamination remains a key issue in ancient DNA research. Currently, human and microbial contaminant DNA still impose challenges on cost-effective sequencing and accurate interpretation of ancient DNA data. RESULTS: Here we investigate whether human contaminating DNA can be found in ancient faunal sequencing datasets. We identify variable levels of human contamination, which persists even after the sequence reads have been mapped to the faunal reference genomes. This contamination has the potential to affect a range of downstream analyses. CONCLUSIONS: We propose a fast and simple method, based on competitive mapping, which allows identifying and removing human contamination from ancient faunal DNA datasets with limited losses of true ancient data. This method could represent an important tool for the ancient DNA field.

Corded Ware cultural complexity uncovered using genomic and isotopic analysis from south-eastern Poland.

During the Final Eneolithic the Corded Ware Complex (CWC) emerges, chiefly identified by its specific burial rites. This complex spanned most of central Europe and exhibits demographic and cultural associations to the Yamnaya culture. To study the genetic structure and kin relations in CWC communities, we sequenced the genomes of 19 individuals located in the heartland of the CWC complex region, south-eastern Poland. Whole genome sequence and strontium isotope data allowed us to investigate genetic ancestry, admixture, kinship and mobility. The analysis showed a unique pattern, not detected in other parts of Poland; maternally the individuals are linked to earlier Neolithic lineages, whereas on the paternal side a Steppe ancestry is clearly visible. We identified three cases of kinship. Of these two were between individuals buried in double graves. Interestingly, we identified kinship between a local and a non-local individual thus discovering a novel, previously unknown burial custom.