Detection of microemboli in patients with acute ischaemic stroke and atrial fibrillation suggests poor functional outcome.

INTRODUCTION: We investigated the burden of microembolic signals (MES) in patients with acute ischaemic stroke (AIS) and atrial fibrillation (AF), assessing their impact on functional outcomes. PATIENTS AND METHODS: This multicentre international prospective cohort study involved patients with AIS and either a known or newly diagnosed anticoagulant-naïve AF. All centres utilised the same transcranial Doppler machine for 1-h monitoring with bilateral 2 MHz probes within 24 h of symptom onset. Recordings underwent MES analysis by a blinded central reader. The primary objectives were to ascertain the MES proportion and its association with functional outcomes assessed by the modified Rankin scale (mRS) score at 90 days. RESULTS: Between September 2019 and May 2021, we enrolled 61 patients, with a median age of 78 years (interquartile range 73-83) and a median stroke severity score of 11 (interquartile range 4-18). MES were observed in 14 patients (23%), predominantly unilateral (12/14, 86%), with a median rate of 6 counts/hour (interquartile range 4-18). MES occurrence was higher post-thrombectomy and among those with elevated brain natriuretic peptide levels (p < 0.05). A worse mRS score of 3-6 was more frequent in patients with MES, occurring in 11/14 (79%), compared to those without MES, 20/47 (43%), with an adjusted odds ratio of 5.04 (95% CI, 1.15-39.4), p = 0.04. CONCLUSIONS: Nearly a quarter of patients with AIS and AF exhibited silent microembolization after the index event. Detecting MES within 24 h post-stroke (using transcranial Doppler) could signify a marker of poor functional outcomes. Subsequent trials will assess if very early antithrombotic treatment might enhance outcomes in this highly selective group of cardioembolic stroke patients. (Clinicaltrials.gov ID: NCT06018090).

The Interconnection between Carotid Intima-Media Thickness and Obesity: Anthropometric, Clinical and Biochemical Correlations.

Background and Objectives: Carotid intima-media thickness (CIMT) and obesity are considered independent determinants of cardio- and cerebrovascular events. The aim of our study was to investigate the effect of obesity on CIMT and to define which traditional cardiovascular risk factors correlate the most with CIMT values in patients with obesity. Materials and Methods: Anthropometric measurements were collected for the whole study group, as well as body composition and blood pressure data, and biochemical blood analyses were also performed. Results: Although our study group was significantly older according to vascular compared with chronological age, the mean CIMT values were lower when compared with the reference values. We found a statistically significant correlation of CIMT with chronological and vascular age, systolic blood pressure, fasting glucose, total cholesterol and triglyceride levels, waist-to-hip ratio, waist circumference, body muscle mass and skeletal muscle mass index. Atherosclerotic Cardiovascular Disease (ASCVD) risk assessment and SCORE (Systematic COronary Risk Evaluation) showed significant positive correlations, but there was only a weak correlation of ASCVD with CIMT. Conclusions: To deduce, since no diagnostic tool currently includes body weight as an individual risk factor, further trials are highly needed to determine if SCORE, SCORE2, ASCVD risk assessment or CIMT would be the most accurate and relevant diagnostic tool for prediction of risk for future CV events in patients with obesity.

Regional and national differences in stroke thrombolysis use and disparities in pricing, treatment availability, and coverage.

BACKGROUND: Major disparities have been reported in recombinant tissue plasminogen activator (rtPA) availability among countries of different socioeconomic status. AIMS: To characterize variability of rtPA price, its availability, and its association with and impact on each country's health expenditure (HE) resources. METHODS: We conducted a global survey to obtain information on rtPA price (50 mg vial, 2020 US Dollars) and availability. Country-specific data, including low, lower middle (LMIC), upper middle (UMIC), and high-income country (HIC) classifications, and gross domestic product (GDP) and HE, both nominally and adjusted for purchasing power parity (PPP), were obtained from World Bank Open Data. To assess the impact of rtPA cost, we computed the rtPA price as percentage of per capita GDP and HE and examined its association with the country income classification. RESULTS: rtPA is approved and available in 109 countries. We received surveys from 59 countries: 27 (46%) HIC, 20 (34%) UMIC, and 12 (20%) LMIC. Although HIC have significantly higher per capita GDP and HE compared to UMIC and LMIC (p < 0.0001), the median price of rtPA is non-significantly higher in LMICs (USD 755, interquartile range, IQR (575-1300)) compared to UMICs (USD 544, IQR (400-815)) and HICs (USD 600, IQR (526-1000)). In LMIC, rtPA cost accounts for 217.4% (IQR, 27.1-340.6%) of PPP-adjusted per capita HE, compared to 17.6% (IQR (11.2-28.7%), p < 0.0001) for HICs. CONCLUSION: We documented significant variability in rtPA availability and price among countries. Relative costs are higher in lower income countries, exceeding the available HE. Concerted efforts to improve rtPA affordability in low-income settings are necessary.

A non-invasive hidden-goal test for spatial orientation deficit detection in subjects with suspected mild cognitive impairment.

BACKGROUND: There is a need for highly sensitive and specific tests and biomarkers that would allow preclinical diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD), which would also enable timely intervention. NEW METHOD: We have developed a new system (ALZENTIA) to help detect early MCI, mainly caused by AD. The system is based on a hidden-goal task (HGT) in which the human subject has to find a target that is not visible; as such, the navigation is based on a previously memorized target position, in relation to the starting position (egocentric variant) and/or other navigational landmarks (allocentric variant of the task). We present our preliminary results obtained in 33 patients with MCI and 91 healthy controls (HC). RESULTS AND COMPARISON WITH EXISTING METHODS: Between-group differences in the average error measured in allocentric, egocentric, and combined allocentric-egocentric subtests were statistically significant in MCI compared to HC. The high negative predictive values suggested high discriminative capacity and diagnostic potential for the HGT test as a tool to detect subjects in healthy population who will progress to MCI. Considering the low sensitivity of the Mini-Mental Status Examination and Montreal Cognitive Assessment tests, we believe that HGT can improve early identification of MCI patients who will progress to AD. CONCLUSION: The HGT carried out with the ALZENTIA system proved to be a reliable screening test to identify individuals with MCI from an aging cohort.

The effect of delayed anti-NMDAR encephalitis recognition on disease outcome.

Anti-NMDA receptor encephalitis is an acute form of brain inflammation that is potentially lethal but has a high probability for recovery with treatment. Although the clinical picture of anti-NMDAR encephalitis is usually recognizable due to its relatively well-known symptoms, the disorder can sometimes present itself in an unpredictable and atypical way. In this case report, we wish to present the influence of different delay times prior to the establishment of diagnosis. Thus, our first patient was diagnosed with anti-NMDAR encephalitis 4 years after the initial symptoms, the second one after 8 years, and the third one after 13 months. The outcomes of the three presented patients indicate the importance of being aware of many clinical presentations of this disorder, as its early diagnosis greatly affects the outcome and may reduce permanent damage, especially in cognitive functions.

Monoaminergic neuropathology in Alzheimer's disease.

None of the proposed mechanisms of Alzheimer's disease (AD) fully explains the distribution patterns of the neuropathological changes at the cellular and regional levels, and their clinical correlates. One aspect of this problem lies in the complex genetic, epigenetic, and environmental landscape of AD: early-onset AD is often familial with autosomal dominant inheritance, while the vast majority of AD cases are late-onset, with the ε4 variant of the gene encoding apolipoprotein E (APOE) known to confer a 5-20 fold increased risk with partial penetrance. Mechanisms by which genetic variants and environmental factors influence the development of AD pathological changes, especially neurofibrillary degeneration, are not yet known. Here we review current knowledge of the involvement of the monoaminergic systems in AD. The changes in the serotonergic, noradrenergic, dopaminergic, histaminergic, and melatonergic systems in AD are briefly described. We also summarize the possibilities for monoamine-based treatment in AD. Besides neuropathologic AD criteria that include the noradrenergic locus coeruleus (LC), special emphasis is given to the serotonergic dorsal raphe nucleus (DRN). Both of these brainstem nuclei are among the first to be affected by tau protein abnormalities in the course of sporadic AD, causing behavioral and cognitive symptoms of variable severity. The possibility that most of the tangle-bearing neurons of the LC and DRN may release amyloid ß as well as soluble monomeric or oligomeric tau protein trans-synaptically by their diffuse projections to the cerebral cortex emphasizes their selective vulnerability and warrants further investigations of the monoaminergic systems in AD.

Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies.

Abnormal deposition of misprocessed and aggregated proteins is a common final pathway of most neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized by the extraneuronal deposition of the amyloid ß (Aß) protein in the form of plaques and the intraneuronal aggregation of the microtubule-associated protein tau in the form of filaments. Based on the biochemically diverse range of pathological tau proteins, a number of approaches have been proposed to develop new potential therapeutics. Here we discuss some of the most promising ones: inhibition of tau phosphorylation, proteolysis and aggregation, promotion of intra- and extracellular tau clearance, and stabilization of microtubules. We also emphasize the need to achieve a full understanding of the biological roles and post-translational modifications of normal tau, as well as the molecular events responsible for selective neuronal vulnerability to tau pathology and its propagation. It is concluded that answering key questions on the relationship between Aß and tau pathology should lead to a better understanding of the nature of secondary tauopathies, especially AD, and open new therapeutic targets and strategies.

Cerebral sinuvenous thrombosis: a rare complication of Lyme neuroborreliosis.

Association between neuroborreliosis and cerebral sinuvenous thrombosis is rare, and it can be made only when other, more common predisposing conditions are excluded. In the case of increased intracranial pressure and confirmed neuroborreliosis, early magnetic resonance venography and combination of antibacterial therapy with anticoagulation provide better long-term outcome. We present a case of a patient with cerebral sinuvenous thrombosis who was first treated for neuroborreliosis.