Optic Nerve Sheath Diameter Point-of-Care Ultrasonography Quality Criteria Checklist: An International Consensus Statement on Optic Nerve Sheath Diameter Imaging and Measurement.

OBJECTIVES: To standardize optic nerve sheath diameter (ONSD) point-of-care ultrasonography (POCUS) and improve its research and clinical utility by developing the ONSD POCUS Quality Criteria Checklist (ONSD POCUS QCC). DESIGN: Three rounds of modified Delphi consensus process and three rounds of asynchronous discussions. SETTING: Online surveys and anonymous asynchronous discussion. SUBJECTS: Expert panelists were identified according to their expertise in ONSD research, publication records, education, and clinical use. A total of 52 panelists participated in the Delphi process. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three Delphi rounds and three asynchronous discussion rounds generated consensus on quality criteria (QC). This started with 29 QC in addition to other QC proposed by expert panelists. The QC items were categorized into probe selection, safety, body position, imaging, measurement, and research considerations. At the conclusion of the study, 28 QC reached consensus to include in the final ONSD POCUS QCC. These QC were then reorganized, edited, and consolidated into 23 QC that were reviewed and approved by the panelists. CONCLUSIONS: ONSD POCUS QCC standardizes ONSD ultrasound imaging and measurement based on international consensus. This can establish ONSD ultrasound in clinical research and improve its utility in clinical practice.

Neurosonology Survey in Europe and Beyond.

Purpose To provide an overview on education, training, practice requirements, and fields of application of neurosonology in Europe and beyond. Materials and Methods National representatives and experts in neurosonology were surveyed regarding neurosonology requirements and practice in their countries. Descriptive statistics were used to report the data. Results Between February 1 and March 31, 2023, 42/46 (91.3%) national representatives responded to our questionnaire and the completion rate was 100%. Most countries (71.4%) offer a neurosonology training program during neurology residency, but it is part of the undergraduate medical program only in 30.9%. National certification is available in 47.6% of the countries surveyed and most countries (76.2%) require certification to practice. In 50% of the countries, candidates are assessed by a board examination, while in 26.2% they just need to document their practice. There is no formal accreditation of neurosonology centers in 78.6% of the countries surveyed. Only a few require certified personnel and appropriate equipment. Adequate teaching and research activities are only rarely necessary elements for laboratory accreditation. Conclusion Our results indicate that there is a substantial need for transnational harmonization of neurosonological standards to guarantee uniformity and quality of performance. This survey will also provide guidance to promote an international accrediting council and create a quality-controlled laboratory network for implementing neurosonology in clinical trials.

Iatrogenic cerebral amyloid angiopathy: A multinational case series and individual patient data analysis of the literature.

BACKGROUND: The transmission of amyloid ß (Aß) in humans leading to iatrogenic cerebral amyloid angiopathy (iCAA) is a novel concept with analogies to prion diseases. However, the number of published cases is low, and larger international studies are missing. AIMS: We aimed to build a large multinational collaboration on iCAA to better understand the clinical spectrum of affected patients. METHODS: We collected clinical data on patients with iCAA from Austria, Croatia, Italy, Slovenia, and Spain. Patients were included if they met the proposed Queen Square diagnostic criteria (QSC) for iCAA. In addition, we pooled data on disease onset, latency, and cerebrospinal fluid (CSF) biomarkers from previously published iCAA cases based on a systematic literature review. RESULTS: Twenty-seven patients (22% women) were included in this study. Of these, 19 (70%) met the criteria for probable and 8 (30%) for possible iCAA. Prior neurosurgical procedures were performed in all patients (93% brain surgery, 7% spinal surgery) at median age of 8 (interquartile range (IQR) = 4-18, range = 0-26 years) years. The median symptom latency was 39 years (IQR = 34-41, range = 28-49). The median age at symptom onset was 49 years (IQR = 43-55, range = 32-70). Twenty-one patients (78%) presented with intracranial hemorrhage and 3 (11%) with seizures. CONCLUSIONS: Our large international case series of patients with iCAA confirms a wide age boundary for the diagnosis of iCAA. Dissemination of awareness of this rare condition will help to identify more affected patients.

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.

Near-Infrared Spectroscopy-Guided, Individualized Arterial Blood Pressure Management for Carotid Endarterectomy under General Anesthesia: A Randomized, Controlled Trial.

Background: Differences in blood pressure can influence the risk of brain ischemia, perioperative complications, and postoperative neurocognitive function in patients undergoing carotid endarterectomy (CEA). Methods: In this single-center trial, patients scheduled for CEA under general anesthesia were randomized into an intervention group receiving near-infrared spectroscopy (NIRS)-guided blood pressure management during carotid cross-clamping and a control group receiving standard care. The primary endpoint was postoperative neurocognitive function assessed before surgery, on postoperative days 1 and 7, and eight weeks after surgery. Perioperative complications and cerebral autoregulatory capacity were secondary endpoints. Results: Systolic blood pressure (p < 0.001) and norepinephrine doses (89 (54-122) vs. 147 (116-242) µg; p < 0.001) during carotid cross-clamping were lower in the intervention group. No group differences in postoperative neurocognitive function were observed. The rate of perioperative complications was lower in the intervention group than in the control group (3.3 vs. 26.7%, p = 0.03). The breath-holding index did not differ between groups. Conclusions: Postoperative neurocognitive function was comparable between CEA patients undergoing general anesthesia in whom arterial blood pressure during carotid cross-clamping was guided using NIRS and subjects receiving standard care. NIRS-guided, individualized arterial blood pressure management resulted in less vasopressor exposition and a lower rate of perioperative complications.

Croatian study on COVID-19-positive stroke patients during the second wave of the pandemic.

AIM: To investigate stroke characteristics in patients with concomitant coronavirus disease 2019 (COVID-19) infection in Croatia during the second wave of the COVID-19 pandemic. METHODS: This retrospective study investigated the characteristics of two groups of ischemic stroke patients: those who developed COVID-19 infection before stroke and those who developed the infection during the hospital stay after stroke onset. Stroke etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. RESULTS: We analyzed data from 255 stroke patients from 12 Croatian hospitals. The two groups of ischemic stroke patients differed in stroke etiology (P=0.038). Patients with COVID-19 infection before stroke had fewer cardioembolic strokes (46% vs 29.1%), more cryptogenic strokes (32.5% vs 14.3%), and more strokes in multiple vascular territories (12.4% vs 1.8%). The percentage of large-vessel occlusions was high in both groups (49.6% and 44.4%). Median modified Rankin Scale score on discharge was 4 in both groups. Mortality was 36.4% in the group with stroke after COVID-19 and 33.3% in the group with COVID-19 after stroke. CONCLUSION: Ischemic stroke after COVID-19 differs in etiology from ischemic stroke complicated by COVID-19 infection. Both patient groups are characterized by severe disability and high mortality. Raising the awareness of prehospital stroke and optimization of clinical workflow are important if we want to improve the stroke outcomes by acute recanalization techniques.

Prevalence and correlates of post-traumatic stress disorder after ischaemic stroke.

Although most often considered a consequence of traumatic event, post-traumatic stress disorder (PTSD) also occurs after illness. The aim of this study was to establish prevalence of PTSD in patients with ischaemic stroke (IS) and its correlation to lesion location, degree of disability, age, gender and marital status. The study included 85 patients with IS. PTSD was diagnosed using a modified version of the PTSD Checklist Specific for a stressor (PCL-S). Depression and anxiety were assessed using Hospital Anxiety and Depression Scale (HADS). We defined stroke localisation as right cerebral hemisphere, left cerebral hemisphere, brainstem and cerebellum. Stroke severity was measured using the modified Rankin scale (mRS). Demographic information including age, gender and marital status was collected from medical history. Of the 85 patients with IS, 11 (12.9%) fulfilled PCL-S criteria for PTSD. We found a positive correlation between PTSD and higher degree of disability, P < 0.001. Patients with PTSD had lesions more frequently localised in the right cerebral hemisphere and the brainstem. We found no statistically significant correlation of PTSD with age, gender and marital status. Our results show that a significant number of IS patients develop PTSD after IS. Determining correlates of post-stroke PTSD can help to identify those at higher risk for its development. If proven by additional large sample studies, more patients can benefit from screening for the PTSD symptoms.

Integration of complementary biomarkers in patients with first episode psychosis: research protocol of a prospective follow up study.

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.

Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection.

BACKGROUND: Neurological complications after coronary artery bypass grafting (CABG) reduce quality of life, increase mortality, and inflate resource utilization. The risk of postoperative neurological complications parallels the increasing risk burden of the contemporary patient population. We evaluated the efficacy of remote ischemic preconditioning (RIPC) on inducing neuroprotection. METHODS: Seventy patients undergoing first-time CABG were randomly assigned to RIPC or a sham procedure. Structural brain magnetic resonance imaging (MRI) was complemented with functional connectivity MRI to gain a whole-brain global connectivity analysis. Paired neurocognitive and MRI data were acquired pre- and postoperatively. The primary end point was a composite of new ischemic brain lesions and neurocognitive impairment. Secondary end points included brain connectivity profiles, pooled ischemic volumes, and individual components of the primary outcome. The Shapiro-Wilk test was used to determine whether a data set followed a normal distribution. The Fisher exact test was used to calculate the measures of association for categorical variables, whereas continuous data were tested with either the Mann-Whitney U test or the Student t test. RESULTS: There was no between-group difference in the incidence of the primary end point (9 [27%] in the RIPC group vs 8 [24%] in the control group, odds ratio, 1.17 [95% confidence interval, 0.34-4.06]; P = 1.0). Although RIPC did not reduce the incidence of brain ischemia (8/33 [24%] vs 7/33 [21%]; P = 1.0), the pooled ischemic volume was lower in the RIPC group (157 [interquartile range, 125-231] vs 777 [interquartile range, 564-965] mm3; P = .004). Postoperative neurocognition was marginally superior in the RIPC group as evidenced by a lower absolute number of abnormal neurocognitive tests in the RIPC group (7/99 [7%] vs 16/99 [16%]; odds ratio, 0.40 [95% confidence interval, 0.14-1.09]; P = .074). Robust reductions of functional connectivity profiles for the associative thalamus were documented in both groups, irrespective of RIPC (RIPC group, t = 3.31; P < .01; and the control group, t = 3.52; P < .01). CONCLUSIONS: Silent brain ischemia occurs frequently after CABG. RIPC did not reduce the incidence of the primary outcome. However, RIPC significantly reduced the pooled volume of ischemic brain lesions. Surgery adversely affected global brain connectivity, with RIPC conferring no demonstrable protection. The association of RIPC with superior neurocognitive test scores failed to cross the threshold for significance.

Significantly lower right middle cerebral artery blood flow velocity in the first episode of psychosis during neurocognitive testing.

BACKGROUND: Changes in cerebral hemodynamics have been reported in schizophrenia and proposed as underlying the cognitive deficits seen in patients. The objective of our study was to compare changes of the cerebral blood flow velocity (BFV) during neurocognitive tasks between the patients with the first episode of psychosis and healthy controls. SUBJECTS AND METHODS: We recruited 46 patients with the first episode of psychosis (FEP), admitted to the University Hospital Centre Zagreb during 2016-2017 and 41 control subjects. Transcranial Doppler ultrasonography monitoring of BFV in both middle cerebral arteries was recorded during 25-minute long neurocognitive assessment with Phonemic Verbal Fluency test, Trial Making Test B and Stroop test. Between every consecutive test resting periods were recorded. RESULTS: After the adjustment for age, sex and education by quantile regression, patients with FEP had significantly lower BFV in middle cerebral arteries during the 3rd (Δ-15, Δ%-28% p=0.023) and 4th task (Δ-15, Δ%-28% p=0.031) of the Stroop test and the 1st task of Foot tapping test (Δ -16, Δ% -30% p=0.034). We observed significantly lower changes of right middle cerebral artery BFV in FEP between two consecutive tests in all four tasks of the Phonemic verbal fluency test, 1st and 2nd task of the Stroop test and Trail making test, and the1st task of Foot tapping test; and of the left artery between first three tasks of the Phonemic verbal fluency test, the last one of the Phonemic verbal fluency test and all first three tasks of the Stroop test. CONCLUSIONS: Decreased middle BFV during the execution of particular neurocognitive tasks in patients with FEP, compared to control subjects might indicate impaired hemodynamic function in the prefrontal/parietal brain areas, and possibly provide an explanation of some of the observed neurocognitive deficits in patients with the first episode of psychosis.

Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimer's disease.

BACKGROUND: The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders. METHODS: At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications. RESULTS: Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine. CONCLUSIONS: US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.

Intravenous Thrombolysis in Unknown-Onset Stroke: Results From the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry.

BACKGROUND AND PURPOSE: Stroke patients with unknown onset (UKO) are excluded from thrombolytic therapy. We aim to study the safety and efficacy of intravenous alteplase in ischemic stroke patients with UKO of symptoms compared with those treated within 4.5 hours in a large cohort. METHODS: Data were analyzed from 47 237 patients with acute ischemic stroke receiving intravenous tissue-type plasminogen activator in hospitals participating in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry between 2010 and 2014. Two groups were defined: (1) patients with UKO (n=502) and (2) patients treated within 4.5 hours of stroke onset (n=44 875). Outcome measures were symptomatic intracerebral hemorrhage per Safe Implementation of Treatment in Stroke on the 22 to 36 hours post-treatment neuroimaging and mortality and functional outcome assessed by the modified Rankin Scale at 3 months. RESULTS: Patients in UKO group were significantly older, had more severe stroke at baseline, and longer door-to-needle times than patients in the ≤4.5 hours group. Logistic regression showed similar risk of symptomatic intracerebral hemorrhage (adjusted odds ratio, 1.09; 95% confidence interval, 0.44-2.67) and no significant differences in functional independency (modified Rankin Scale score of 0-2; adjusted odds ratio, 0.79; 95% confidence interval, 0.56-1.10), but higher mortality (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.41) in the UKO group compared with the ≤4.5 hours group. Patients treated within 4.5 hours showed reduced disability over the entire range of modified Rankin Scale compared with the UKO group (common adjusted odds ratio, 1.29; 95% confidence interval, 1.01-1.65). CONCLUSIONS: Our data suggest no excess risk of symptomatic intracerebral hemorrhage but increased mortality and reduced favorable outcome in patients with UKO stroke compared with patients treated within the approved time window.

A High Burden of Ischemic Stroke in Regions of Eastern/Central Europe is Largely Due to Modifiable Risk Factors.

Incidence and mortality of ischemic stroke in Croatia is significantly higher than in many other developed European countries. Here, we aimed to evaluate underlying conditions of this unacceptably high disease burden. An observational prospective cohort study of first-ever ischemic stroke patients identified in a population-based incidence study (N=751) (study 1, S1) and a concurrent case-control trial (215 patients, 125 controls, S2) were conducted in the county of Varazdin from 2007-2010. Atrial fibrillation (AF) was common (36.1% in S1, 40.9% in S2) and mostly (>50%) unrecognized before the index event. In a multivariate analysis, odds of stroke increased with tobacco smoking (OR=3.95, 95%CI 1.33-10.8), unhealthy diet (OR=2.12, 1.12-4.01) and AF (OR=9.40, 4.01-22.0), and decreased with higher education (OR=0.33, 0.11-0.98), moderate alcohol consumption (OR=0.48, 0.25-0.93), higher fasting HDL (OR=0.14, 0.07-0.30) and pre-stroke use of anticoagulants (OR=0.09, 0.01-0.59), antihypertensive drugs (OR=0.52, 0.27-1.00) and statins (OR=0.29, 0.12-0.69). Fourteen-day case fatality was 10.8% (S1) and 6.1% (S2) and the risk was higher with AF, cardioembolic stroke, older age, higher fasting serum glucose, and lower with acute aspirin. Among the acute phase survivors, 30.9% died over the subsequent 1-3 years (p<0.05). We conclude that the incidence of ischemic stroke in Croatia is related to conventional risk factors and largely due to a high rate of unawareness and inadequate treatment of predisposing morbidity.

Control of main risk factors after ischaemic stroke across Europe: data from the stroke-specific module of the EUROASPIRE III survey.

BACKGROUND: Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking. METHODS: A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6-36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines. RESULTS: A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index ≥30 kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines. CONCLUSION: The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines.

Impact of remote ischemic preconditioning preceding coronary artery bypass grafting on inducing neuroprotection (RIPCAGE): study protocol for a randomized controlled trial.

BACKGROUND: Neurological complications after cardiac surgery have a profound impact on postoperative survival and quality of life. The increasing importance of strategies designed to improve neurological outcomes mirrors the growing risk burden of the contemporary cardiac surgical population. Remote ischemic preconditioning (RIPC) reduces adverse sequelae of ischemia in vulnerable organs by subjecting tissues with high ischemic tolerance to brief periods of hypoperfusion. This trial will evaluate the neuroprotective effect of RIPC in the cardiac surgical arena, by employing magnetic resonance imaging (MRI) and neurocognitive testing. METHODS: Patients scheduled for elective coronary artery bypass grafting with the use of cardiopulmonary bypass will be screened for the study. Eligible patients will be randomized to undergo either a validated RIPC protocol or a sham procedure. The RIPC will be induced by inflation of a blood pressure cuff to 200 mmHg for 5 minutes, followed by a 5-minute reperfusion period. Three sequences of interchanging cuff inflations and deflations will be employed. Neurocognitive testing and MRI imaging will be performed preoperatively and on postoperative day 7. Paired pre- and postoperative neurocognitive and neuroimaging data will then be compared. The primary composite outcome measure will consist of new ischemic lesions on brain MRI, postprocedural impairment in brain connectivity on resting-state functional MRI (rs-fMRI), and significant new declines in neurocognitive performance. The secondary endpoint measures will be the individual components of the primary endpoint measures, expressed as continuous variables, troponin T release on postoperative day 1 and the incidence of major adverse cardiovascular events at 3 months postoperatively. Major adverse cardiovascular events, including accumulating cardiovascular mortality, stroke, nonfatal myocardial infarction, and rehospitalization for ischemia, will form a composite endpoint measure. DISCUSSION: This trial will aim to assess whether RIPC in patients subjected to surgical myocardial revascularization employing cardiopulmonary bypass initiates a neuroprotective response. Should the results of this trial indicate that RIPC is effective in reducing the incidence of adverse neurological events in patients undergoing coronary artery bypass grafting, it could impact on the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov NCT02177981.

Hemodynamic monitoring of middle cerebral arteries during cognitive tasks performance.

AIM: The aim of this study was to obtain temporal pattern and hemispheric dominance of blood flow velocity (BFV) changes and to assess suitability of different cognitive tasks for monitoring of BFV changes in the middle cerebral arteries (MCA). METHODS: BFV were recorded simultaneously in MCA during performance of phonemic verbal fluency test (pVFT), Trail Making Tests A and B (TMTA and TMTB) and Stroop tests in 14 healthy, right-handed volunteers aged 20-26 years. RESULTS: A significant increase of BFV in both MCA was obtained during performance of all cognitive tasks. Statistically significant lateralization was found during performance of Stroop test with incongruent stimuli, while TMTB was found to have the best activation potential for MCA. CONCLUSION: Our findings specify TMTB as the most suitable cognitive test for monitoring of BFV in MCA.

Blood flow velocity changes in anterior cerebral arteries during cognitive tasks performance.

OBJECTIVE: Transcranial Doppler sonography (TCD) enables monitoring of blood flow velocities (BFVs) in basal cerebral arteries during different cognitive tasks performance with great temporal resolution. So far, BFVs changes during mental activity were monitored primarily in middle cerebral arteries (MCAs) and little is known about these changes in anterior cerebral arteries (ACAs). AIM: To determine the effect of different cognitive tasks performance on BFV changes and hemispheric dominance in ACAs and to assess the most suitable activation test for monitoring of BFV changes in ACAs. METHODS: Fourteen right-handed, healthy subjects aged 20-26 were included in the study. BFVs in both ACAs were recorded simultaneously during performance of cognitive tasks designed to activate frontal lobes: phonemic verbal fluency test (pVFT), Stroop tests and Trail Making Tests (TMTs). RESULTS: A statistically significant BFV increase was recorded in both ACAs during performance of all cognitive tasks. Statistically significant right ACA dominance was found during performance of pVFT and TMTB. The most significant BFV increase was obtained during performance of TMTB. CONCLUSION: Our result addressed cognitive tests with great activation potential for monitoring of ACAs that might be used in distinguishing of healthy individuals and patients with neurovascular or neurodegenerative diseases.

Single aortic clamping in coronary artery bypass surgery reduces cerebral embolism and improves neurocognitive outcomes.

Aortic manipulation releases embolic material, thereby enhancing the probability of adverse neurologic outcomes following coronary artery bypass grafting (CABG). We prospectively evaluated 59 patients undergoing CABG. Patients in the single (SC, n = 37) and multiple clamp (MC, n = 22) groups were comparable in relation to age and operative risk (p > 0.05). Neurocognitive evaluation consisted of the Auditory Verbal Learning Test (AVLT), Color Trails Test A, the Grooved Pegboard test and the Mini-Mental State Examination. Data acquisition was performed preoperatively, early postoperatively and at the 4-month follow-up. Intraoperative transcranial Doppler (TCD) monitoring was used to quantify the embolic load in relation to different aortic clamping strategies. Preoperative neurocognitive results were similar between the groups (p > 0.05). The incidence of postoperative delirium was greater in the MC group but this failed to reach statistical significance (23% vs 8%, p = 0.14). SC patients had fewer embolization signals (270 ± 181 vs 465 ± 160, p < 0.0001). Early postoperative neurocognitive results were depressed in comparison to preoperative values in both groups (p < 0.05 for multiple comparisons). The magnitude of this cognitive depression was greater in the MC group (p < 0.05 for multiple comparisons). Preoperative levels of neurocognition were restored at follow-up in the SC group in all tests except the AVLT. A trend towards improvements in neurocognitive performances at follow-up was also observed in the MC group. Residual attention, motor skill and memory deficits were, however, documented with multiple tests. In conclusion, the embolic burden was significantly lower in the SC group. This TCD imaging outcome translated into fewer early cognition deficits and superior late restoration of function.