Comparison of pre-mortem 2D-3D ultrasound examination to post-mortem micro-CT of carotid arteries - first experiences.

Background and purpose:

A prerequisite for the treatment of carotid atherosclerosis is the accurate measurement of the stenosis, that is most commonly evaluated by duplex ultrasonography. In this study, we aimed to verify the reliability of 2D and 3D ultrasonography, comparing the data to results of post-mortem micro-CT examination.

Neurological patients with any life-threatening, presumably fatal neurological disease were enrolled. Ultrasound examinations were performed with a Philips Epiq 5G machine, using a VL13-5 broadband linear volume array transducer. Plaque length, diameter and vessel area reduction (stenosis) were calculated using the 2D images. Finally, the stenosis was reassessed using automatized, 3D application as well. After the death of the patient, autopsy was performed, during which the previously examined carotid artery was removed. The samples were examined with micro-CT. Similar to the ultrasound examination, plaque length, diameter and vessel area reduction (stenosis) were determined.

Ten vessels of seven patients were eligible for complex comparison. Plaque diameter and length measured by CT did not correlate with the ultrasound data. CT-measured axial plaque and vessel areas showed no correlation with ultrasound results either. While determining the strength of correlation between stenoses measured by the different modalities, significant correlation was found between the results measured by ultrasound (2D) and CT (Pearson r: 0.902, P<0.001).

Three-dimensional ultrasound analysis is a spectacular method for examining carotid plaques, as it can assist in a more detailed evaluation of the plaque morphology and composition, thereby identifying plaques with a particularly high risk of stroke. Micro-CT is an excellent tool for the exact determination of calcified plaque areas, but ultrasound images are not suitable yet for such a precise examination due to acoustic shadowing and artifacts.

Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.

Background: Infections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke. Methods: We conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR < 1 suggests benefit and an acOR > 1 harm). This trial is registered (ISRCTN82217627). Findings: From April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81-1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77-1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96-1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events. Interpretation: We observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke. Funding: This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No: 634809.

Enalapril Is Superior to Lisinopril in Improving Endothelial Function without a Difference in Blood-Pressure-Lowering Effects in Newly Diagnosed Hypertensives.

Angiotensin-converting enzyme (ACE) inhibitors are the primarily chosen drugs to treat various cardiovascular diseases, such as hypertension. Although the most recent guidelines do not differentiate among the various ACE inhibitory drugs, there are substantial pharmacological differences. GOAL: Here, we tested if lipophilicity affects the efficacy of ACE inhibitory drugs when used as the first therapy in newly identified hypertensives in a prospective study. METHODS: We tested the differences in the cardiovascular efficacy of the hydrophilic lisinopril (8.3 ± 3.0 mg/day) and the lipophilic enalapril (5.5 ± 2.3 mg/day) (n = 59 patients). The cardiovascular parameters were determined using sonography (flow-mediated dilation (FMD) in the brachial artery, intima-media thickness of the carotid artery), 24 h ambulatory blood pressure monitoring (peripheral arterial blood pressure), and arteriography (aortic blood pressure, augmentation index, and pulse wave velocity) before and after the initiation of ACE inhibitor therapy. RESULTS: Both enalapril and lisinopril decreased blood pressure. However, lisinopril failed to improve arterial endothelial function (lack of effects on FMD) when compared to enalapril. Enalapril-mediated improved arterial endothelial function (FMD) positively correlated with its blood-pressure-lowering effect. In contrast, there was no correlation between the decrease in systolic blood pressure and FMD in the case of lisinopril treatment. CONCLUSION: The blood-pressure-lowering effects of ACE inhibitor drugs are independent of their lipophilicity. In contrast, the effects of ACE inhibition on arterial endothelial function are associated with lipophilicity: the hydrophilic lisinopril was unable to improve, while the lipophilic enalapril significantly improved endothelial function. Moreover, the effects on blood pressure and endothelial function did not correlate in lisinopril-treated patients, suggesting divergent mechanisms in the regulation of blood pressure and endothelial function upon ACE inhibitory treatment.

Role of carotid duplex in the assessment of carotid artery restenosis after endarterectomy or stenting.

Introduction: Redo carotid endarterectomy (CEA) and carotid stenting (CAS) are often performed when there is evidence of post-procedural restenosis. The incidence of restenosis after carotid reconstruction is not negligible, ranging from 5 to 33%. The diagnosis of significant internal carotid artery (ICA) restenosis is usually based on duplex ultrasound (US) criteria, mostly on peak-systolic flow velocity (PSV). However, there have been no generally accepted duplex US criteria for carotid restenosis after CAS or CEA. Methods: In this systematic review, the PubMed/ Medline and Scopus databases were screened to find trials that reported duplex US criteria for significant restenosis after CEA and/or CAS. Only those reports were analyzed in which the restenoses were also assessed by CT/MR or digital subtraction angiography as comparators for duplex US. Results: Fourteen studies met the predetermined search criteria and were included in this review. In most studies, PSV thresholds for significant in-stent ICA restenosis after CAS were higher than those for significant stenosis in non-procedurally treated (native) ICA. Many fewer studies investigated the US criteria for ICA restenosis after CEA. Despite the heterogeneous data, there is a consensus to use higher flow velocity thresholds for assessment of stenosis in stented ICA than in native ICA; however, there have been insufficient data about the flow velocity criteria for significant restenosis after CEA. Although the flow velocity thresholds for restenosis after CAS and CEA seem to be different, the large studies used the same duplex criteria to define restenosis after the two procedures. Moreover, different studies used different flow velocity thresholds to define ICA restenosis, leading to variable restenosis rates. Discussion: We conclude that (1) further examinations are warranted to determine appropriate duplex US criteria for restenosis after CAS and CEA, (2) single duplex US parameter cannot be used to reliably determine the degree of ICA restenosis, (3) inappropriate US criteria used in large studies may have led to false restenosis rates, and (4) studies are required to determine if there is a benefit from redo carotid artery procedure, such as redo-CEA or redo-CAS, starting with prospective risk stratification studies using current best practice non-invasive care alone.

Hemorrhagic Transformation of Ischemic Strokes.

Ischemic stroke, resulting from insufficient blood supply to the brain, is among the leading causes of death and disability worldwide. A potentially severe complication of the disease itself or its treatment aiming to restore optimal blood flow is hemorrhagic transformation (HT) increasing morbidity and mortality. Detailed summaries can be found in the literature on the pathophysiological background of hemorrhagic transformation, the potential clinical risk factors increasing its chance, and the different biomarkers expected to help in its prediction and clinical outcome. Clinicopathological studies also contribute to the improvement in our knowledge of hemorrhagic transformation. We summarized the clinical risk factors of the hemorrhagic transformation of ischemic strokes in terms of risk reduction and collected the most promising biomarkers in the field. Also, auxiliary treatment options in reperfusion therapies have been reviewed and collected. We highlighted that the optimal timing of revascularization treatment for carefully selected patients and the individualized management of underlying diseases and comorbidities are pivotal. Another important conclusion is that a more intense clinical follow-up including serial cranial CTs for selected patients can be recommended, as clinicopathological investigations have shown HT to be much more common than clinically suspected.

[In memoriam László Molnár: statue unveiling at the University of Debrecen]. / In memoriam Molnár László: szoboravatás a Debreceni Egyetemen.

Professor László Molnár was born in 1923. He completed his university studies in Szeged and continued his clinical work in Pécs. He qualified as a neurologist, psychiatrist and neurosurgeon. He first studied the regulation of cerebral blood circulation in animal experiments in Germany, and then worked in Paris as a fellow with Professor Seylaz. He obtained his doctorate at the Sorbonne. He obtained his Candidate’s thesis in 1966 and his Doctorate in 1977. Between 1969 and 1992 he was Head of the Neurological Clinic of the University of Debrecen, where he studied the consequences of focal ischemia in animal experiments. In Debrecen he founded the Cerebrovascular Department, the second in Europe to specialize in the care of stroke patients. Eleven of his staff became senior physicians, four became university professors, and six received PhDs and three MTA doctorates. He died in 1999.

Elevated Blood Alcohol Concentration Is Associated with Improved Clinical Outcomes of Intravenous Thrombolysis Treatment in Acute Ischemic Stroke Patients-A Retrospective Study.

BACKGROUND: Intravenous thrombolysis (IVT) improves acute ischemic stroke (AIS) outcomes, but with limited success. In addition, ethanol potentiates the effect of r-tPA in ischemia models. METHODS: The effect of acute alcohol consumption on IVT outcomes was investigated in a retrospective cohort study. AIS patients with detectable blood alcohol concentration (BAC) during IVT were included (alcohol group; n = 60). For each case, 3 control subjects who underwent IVT but denied alcohol consumption were matched in terms of age, sex, affected brain area, and stroke severity. Outcomes were determined using the NIHSS at 7 days and the modified Rankin scale (mRS) at 90 days. RESULTS: Patients were younger and had a less severe stroke than in a standard stroke study. Favorable long-term outcomes (mRS 0-2) occurred significantly more frequently in the alcohol group compared to controls (90% vs. 63%, p < 0.001). However, the rates of hemorrhagic transformation were similar. Multiple logistic regression models identified elevated BAC as a significant protective factor against unfavorable short-term (OR: 0.091, 95% CI: 0.036-0.227, p < 0.001) and long-term outcomes (OR: 0.187, 95% CI: 0.066-0.535, p = 0.002). In patients with BAC > 0.2%, significantly lower NIHSS was observed at 3 and 7 days after IVT vs. in those with 0.01-0.2% ethanol levels. CONCLUSION: Elevated BAC is associated with improved outcomes in IVT-treated AIS without affecting safety.

The Correlation between Two Angiotensin-Converting Enzyme Inhibitor's Concentrations and Cognition.

Both lisinopril and enalapril are angiotensin-converting enzyme (ACE) drugs and widely used in the treatment of hypertension. Enalapril does not cross the blood-brain barrier, but lisinopril is centrally active. Our goal was to find out if there was a link between the actual concentration of ACE inhibitors and cognition and if there was a detectable difference between the two types of ACE inhibitors. Asymptomatic, non-treated patients were diagnosed by screening and the hypertension was confirmed by ambulatory blood pressure monitoring (ABPM). A battery of cognitive tests was used to assess the impact of randomly assigning participants to receive either lisinopril or enalapril. All neurocognitive functions were measured, especially the most affected by conditions of compromised perfusion pressures, such as hypertension, which are attention and executive functions. The lisinopril concentration showed a significant inverse correlation with mosaic test (coeff. = -0.5779) and seemed to have a significant negative effect on perceptual motor skills (coeff. = -0.5779), complex attention (coeff. = -0.5104) and learning (coeff. = -0.5202). Compared with enalapril, lisinopril is less successful in improving the components of cognitive functions.

Assessment of malformations, variations and diameters of vessels forming the circle of Willis - An autopsy study in a non-cerebrovascular cohort.

Background a purpose: The collateral capacity of the circle of Willis (CoW) may play an important role in the development of ischemic strokes. The occurrence of classical polygon shows wide geographical variations and morphological data on diameters of the Willisian collaterals are scarce. We aimed to assess CoW variations and vessel diameters in a Central European cohort. Subjects and methods: CoWs were removed during routine autopsy. The morphological pattern of the circles was recorded. The prepared circles were then put between two glass plates and tightly compressed. The length of the vessels and half of the circumference were measured under a light microscope enabling measurement with an approximation of 0.1 mm. Vessel diameters were calculated from vessel circumference. Results: A total of 110 circles were analysed. Incomplete circles (missing one or two segments of CoW) were found in 25 cases (22.7%). Any forms of anatomical variations were detected in 14 cases (12.7%). When applying the <1 mm diameter threshold for analysis, 36 anterior communicating arteries (32.7%), 53 right posterior communicating arteries (48.2%), 73 left posterior communicating arteries (66.4%) and 18 posterior communicating arteries (16.3%) on both the sides were considered hypoplastic. Conclusions: In patients without stroke in their history, complete CoW may be present in >60% of the cases. Our diameter data may serve as reference values for the Central-European population.

Thrombin generation as a predictor of outcomes in patients with non-traumatic intracerebral hemorrhage.

Background: Non-traumatic intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes and leads to a higher rate of mortality as compared to ischemic strokes. We aimed to find out whether the thrombin generation assay (TGA) could predict outcomes in patients with ICH. Patients and methods: In this prospective, observational study, 87 consecutive patients with ICH and 164 healthy controls were included. Computed tomography (CT), detailed clinical investigation, and laboratory investigations were performed from patients on admission. TGA was performed using stored platelet poor plasma obtained on admission. Lag time, endogen thrombin potential (ETP), peak thrombin, and time to peak parameters were calculated. Short- and long-term outcomes of ICH were defined at 14 days and 3 months post-event according to the NIHSS and the modified Rankin Scale (mRS), respectively. Results: Peak thrombin was significantly higher in patients as compared to controls (397.2 ± 93.9 vs. 306 ± 85.3 nM, p < 0.0001). Lag time, ETP, and time to peak parameters showed a significant positive correlation with CRP in both groups. In patients with worse long-term functional outcomes, peak thrombin was significantly higher as compared to those with favorable outcomes [mRS 2-6 median: 402.5 (IQR:344.8-473.8) vs. mRS 0-1: 326.4 (294.2-416.1) nM, p = 0.0096]. Based on the statistically optimal threshold of 339.1 nM peak thrombin, the sensitivity and specificity of this parameter to determine mRS 2-6 as an outcome were 80.8 and 64.7%, respectively. In a binary logistic regression model including age, sex, BMI, smoking status, NIHSS on admission, D-dimer, and peak thrombin (>339.1 nM), only NIHSS and the peak thrombin parameters remained in the model as significant, independent predictors of poor outcome. Lag time and time to peak showed a modest, significant negative correlation with intracerebral bleeding volume on admission (r = -0.2603, p = 0.0231 and r = -0.3698, p = 0.0010, respectively). During the follow-up of patients, estimated hemorrhage volumes on day 90 showed significant positive association with the ETP and peak thrombin parameters (r = 0.3838, p = 0.0363 and r = 0.5383, p = 0.0021, respectively). Conclusion: In patients with ICH, TG was increased as compared to healthy controls, which might be explained by the presence of higher inflammatory parameters in patients. Peak thrombin measured on admission might be a useful tool to predict outcomes in patients with ICH.

Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. METHODS: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26-52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. FINDINGS: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0-4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79-1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93-1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85-1·32]; t statistic -0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91-2·71]). INTERPRETATION: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. FUNDING: Bayer AG.

Low α2-Plasmin Inhibitor Antigen Levels on Admission Are Associated With More Severe Stroke and Unfavorable Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background: Intravenous administration of recombinant tissue plasminogen activator (rt-PA) fails to succeed in a subset of acute ischemic stroke (AIS) patients, while in approximately 6-8% of cases intracerebral hemorrhage (ICH) occurs as side effect. Objective: Here, we aimed to investigate α2-plasmin inhibitor (α2-PI) levels during thrombolysis and to find out whether they predict therapy outcomes in AIS patients. Patients/Methods: In this prospective, observational study, blood samples of 421 AIS patients, all undergoing i.v. thrombolysis by rt-PA within 4.5 h of their symptom onset, were taken before and 24 h after thrombolysis. In a subset of patients (n = 131), blood was also obtained immediately post-lysis. α2-PI activity and antigen levels were measured by chromogenic assay and an in-house ELISA detecting all forms of α2-PI. α2-PI Arg6Trp polymorphism was identified in all patients. Stroke severity was determined by NIHSS on admission and day 7. Therapy-associated ICH was classified according to ECASSII. Long-term outcomes were defined at 3 months post-event by the modified Rankin Scale (mRS). Results: Median α2-PI activity and antigen levels showed a significant drop immediately post-lysis and increased to subnormal levels at 24 h post-event. Admission α2-PI levels showed a significant negative stepwise association with stroke severity. Patients with favorable long-term outcomes (mRS 0-1) had significantly higher admission α2-PI antigen levels (median:61.6 [IQR:55.9-70.5] mg/L) as compared to patients with poor outcomes (mRS 2-5: median:59.7 [IQR:54.5-69.1] and mRS 6: median:56.0 [IQR:48.5-61.0] mg/L, p < 0.001). In a Kaplan-Meier survival analysis, patients with an α2-PI antigen in the highest quartile on admission showed significantly better long-term survival as compared to those with α2-PI antigen in the lowest quartile (HR: 4.54; 95%CI:1.92-10.8, p < 0.001); however, in a multivariate analysis, a low admission α2-PI antigen did not prove to be an independent risk factor of poor long-term outcomes. In patients with therapy-related ICH (n = 34), admission α2-PI antigen levels were significantly, but only marginally, lower as compared to those without hemorrhage. Conclusions: Low α2-PI antigen levels on admission were associated with more severe strokes and poor long-term outcomes in this cohort. Our results suggest that in case of more severe strokes, α2-PI may be involved in the limited efficacy of rt-PA thrombolysis.

The neuropeptide landscape of human prefrontal cortex.

Human prefrontal cortex (hPFC) is a complex brain region involved in cognitive and emotional processes and several psychiatric disorders. Here, we present an overview of the distribution of the peptidergic systems in 17 subregions of hPFC and three reference cortices obtained by microdissection and based on RNA sequencing and RNAscope methods integrated with published single-cell transcriptomics data. We detected expression of 60 neuropeptides and 60 neuropeptide receptors in at least one of the hPFC subregions. The results reveal that the peptidergic landscape in PFC consists of closely located and functionally different subregions with unique peptide/transmitter-related profiles. Neuropeptide-rich PFC subregions were identified, encompassing regions from anterior cingulate cortex/orbitofrontal gyrus. Furthermore, marked differences in gene expression exist between different PFC regions (>5-fold; cocaine and amphetamine-regulated transcript peptide) as well as between PFC regions and reference regions, for example, for somatostatin and several receptors. We suggest that the present approach allows definition of, still hypothetical, microcircuits exemplified by glutamatergic neurons expressing a peptide cotransmitter either as an agonist (hypocretin/orexin) or antagonist (galanin). Specific neuropeptide receptors have been identified as possible targets for neuronal afferents and, interestingly, peripheral blood-borne peptide hormones (leptin, adiponectin, gastric inhibitory peptide, glucagon-like peptides, and peptide YY). Together with other recent publications, our results support the view that neuropeptide systems may play an important role in hPFC and underpin the concept that neuropeptide signaling helps stabilize circuit connectivity and fine-tune/modulate PFC functions executed during health and disease.

High Neutrophil-Lymphocyte Ratio and Low Lymphocyte-Monocyte Ratio Combination after Thrombolysis Is a Potential Predictor of Poor Functional Outcome of Acute Ischemic Stroke.

(1) Background: Ischemic stroke is one of the leading causes of death and disability. An inflammatory response is observed in multiple stages of cerebral ischemia, particularly in the acute phase. Recent publications revealed that the neutrophil−lymphocyte ratio (NLR) and lymphocyte−monocyte ratio (LMR) may be used to predict long-term prognosis in acute ischemic stroke (AIS) after thrombolysis. To test whether there is a relationship between the combination of these parameters and long-term prognosis, we analyzed the NLR−LMR combination in AIS patients treated with intravenous recombinant tissue plasminogen activator (rtPA); (2) Methods: The study included 285 adults with a diagnosis of AIS and rtPA treatment within a 4.5 h time window. Blood samples were obtained at admission and 24 h after thrombolysis to calculate pre- and post-thrombolysis NLR and LMR. Clinical data, including NIHSS was registered on admission and day 1. The long-term outcome was defined 90 days post-event by the modified Rankin Scale (mRS). Therapy-associated intracranial hemorrhage (ICH) was classified according to ECASS II. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs of NLR and LMR as predictors of therapy outcomes; (3) Results: Patients were stratified by cutoffs of 5.73 for NLR and 2.08 for LMR. The multivariate logistic regression model, including all possible confounders, displayed no significant association between NLR or LMR with 3-months functional prognosis. The combination of high NLR−low LMR vs. low NRL−high LMR as obtained 24 h after thrombolysis was found to be an independent predictor of poor 3-months functional outcome (mRS ≥ 2; OR 3.407, 95% CI 1.449 to 8.011, p = 0.005). The proportion of patients between low NLR−high LMR and high NLR−low LMR groups from admission to day 1 showed no significant change in the good outcome group. On the other hand, in the poor outcome group (mRS ≥ 2), low NLR−high LMR and high NLR−low LMR groups displayed a significant shift in patient proportions from 67% and 21% at admission (p = 0.001) to 36% and 49% at 24 h after thrombolysis (p < 0.001), respectively; (4) Conclusions: Our study demonstrated for the first time that a high NLR−low LMR combination as observed at 24 h after thrombolysis can serve as an independent predictor of 3-months poor outcome in AIS patients. This simple and readily available data may help clinicians to improve the prognostic estimation of patients and may provide guidance in selecting patients for personalized and intensified care post-thrombolysis.

Evidence for postnatal neurogenesis in the human amygdala.

The human amygdala is involved in processing of memory, decision-making, and emotional responses. Previous studies suggested that the amygdala may represent a neurogenic niche in mammals. By combining two distinct methodological approaches, lipofuscin quantification and 14C-based retrospective birth dating of neurons, along with mathematical modelling, we here explored whether postnatal neurogenesis exists in the human amygdala. We investigated post-mortem samples of twelve neurologically healthy subjects. The average rate of lipofuscin-negative neurons was 3.4%, representing a substantial proportion of cells substantially younger than the individual. Mass spectrometry analysis of genomic 14C-concentrations in amygdala neurons compared with atmospheric 14C-levels provided evidence for postnatal neuronal exchange. Mathematical modelling identified a best-fitting scenario comprising of a quiescent and a renewing neuronal population with an overall renewal rate of >2.7% per year. In conclusion, we provide evidence for postnatal neurogenesis in the human amygdala with cell turnover rates comparable to the hippocampus.

Discrepancies between clinical and autopsy findings in patients who had an acute stroke.

OBJECTIVES: According to international observations, the incidence of clinical autopsies is declining worldwide, plummeting below 5% in the USA and many European countries. It is an unfavourable trend as, in 7%-12% of cases, recent clinicopathological studies found discrepancies that might have changed the therapy or the outcome if known premortem. As previous large-scale observations have examined varied patient populations, we aimed to focus on the differences between the clinical and pathological diagnostic findings in only patients who had a stroke. MATERIAL AND METHODS: We assessed the postmortem non-neuropathological and neuropathological findings of 534 consecutive patients who had a stroke who passed away. Systemic neoplasms, pneumonias, thromboembolisms and haemorrhagic transformations revealed only by autopsy were considered severe abnormalities; in addition, benign abnormalities important from an educational or scientific point of view were also recorded. RESULTS: In 26 of the 534 cases (4.9%), the presence of systemic neoplasms had already been confirmed in the clinical stage; however, 8 (1.5%) malignant tumours were only detected during autopsy. Also, 80 (15%) thromboembolic events, 73 (13.6%) pneumonias and 66 (18%) haemorrhagic transformations were only diagnosed at autopsy. Longer hospital stay (from admission to death) resulted in fewer discrepancies between clinical and autopsy diagnosis of thromboembolic events and pneumonias (p<0.01). In 169 cases, benign findings were detected. CONCLUSIONS: While the type of acute stroke is reliably diagnosed with imaging techniques, postmortem autopsies are also important in patients who had a stroke as autopsies may reveal clinically silent diseases (eg, tumour), and contribute to knowing the actual incidence of stroke-related thromboembolic and pneumonia complications.

Effects of acute alcohol consumption on neuronal activity and cerebral vasomotor response.

INTRODUCTION: In the majority of European countries, driving after drinking small-moderate amount of alcohol is legal. Motivated by our previous studies on cerebral hemodynamics, we aimed to study whether a small-moderate blood alcohol content (BAC), at which driving is legal in some countries (0.8 g/L), influences the neuronal activity, neurovascular coupling, and cerebral vasoreactivity. METHODS: Analyses of pattern-reversal visual evoked potential (VEP) and transcranial Doppler (TCD) examinations were performed in thirty young healthy adults before and 30 min after alcohol consumption. Cerebral vasoreactivity was evaluated by breath holding test in both middle cerebral arteries. By using a visual cortex stimulation paradigm, visually evoked flow velocity response during reading was measured in both posterior cerebral arteries (PCA). RESULTS: The BAC was 0.82 g/L and 0.94 g/L 30 and 60 min after drinking alcohol, respectively. Latency of the VEP P100 wave increased after alcohol consumption. Resting absolute flow velocity values increased, whereas pulsatility indices in the PCA decreased after alcohol ingestion, indicating vasodilation of cerebral microvessels. Breath holding index and the visually evoked maximum relative flow velocity increase in the PCA and steepness of rise of the flow velocity curve were smaller after than before alcohol consumption. CONCLUSION: BAC close to a legal value at which driving is allowed in some European countries inhibited the neuronal activity and resulted in dilation of cerebral arterioles. Cerebral vasodilation may explain the decrease of cerebral vasoreactivity and might contribute to the disturbance of visually evoked flow response after alcohol consumption.

Neurophysiological Examinations as Adjunctive Tool to Imaging Techniques in Spontaneous Intracerebral Hemorrhage: IRONHEART Study.

Introduction: Intracerebral hemorrhage (ICH) is a devastating disease, which may lead to severe disability or even death. Although many factors may influence the outcome, neurophysiological examinations might also play a role in its course. Our aim was to examine whether the findings of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) can predict the prognosis of these patients. Methods: Between June 1 2017 and June 15 2021, 116 consecutive patients with ICH were enrolled prospectively in our observational study. Clinical examinations and non-Contrast computed tomography (NCCT) scan were done on admission for ICH; follow-up NCCT scans were taken at 14 ± 2 days and at 3 months ± 7 days after stroke onset. EEG and TMS examinations were also carried out. Results: Of the patients in the study, 65.5% were male, and the mean age of the study population was 70 years. Most patients had a history of hypertension, 50.8% of whom had been untreated. In almost 20% of the cases, excessive hypertension was measured on admission, accompanied with >10 mmol/L blood glucose level, whereas their Glasgow Coma Scale was 12 on average. Presence of blood in the ventricles or subarachnoid space and high blood and perihematomal volumes meant poor prognosis. Pathological EEG was prognostic of a worse outcome. With TMS examination at 14 days, it might be possible to estimate outcome in a univariate model and the absence, or reduction of the amplitude of the motor evoked potentials was associated with poor prognosis. Conclusion: Together with the clinical symptoms, the volume of bleeding, perihematomal edema (or their combined volume), and neurophysiological examinations like EEG and TMS play an important role in the neurological outcome of patients with ICH. This might affect the patients' rehabilitation plans in the future, since with the help of the examinations the subset of patients with potential for recovery could be identified.