Feasibility of a patient-oriented navigation programme for patients with lung cancer or stroke in Germany: Protocol of the CoreNAVI study.

BACKGROUND: Patient navigation programmes were introduced in the United States and recently gained interest in Germany, where the health care system is fragmented. Navigation programmes aim to decrease barriers to care for patients with age-associated diseases and complex care paths. Here we describe a feasibility study to evaluate a patient-oriented navigation model that was developed in a first project phase by integrating data about barriers to care, vulnerable patient populations and existing support services. METHODS: We designed a mixed-methods feasibility study that consists of two two-arm randomized controlled trials aligned with observational cohorts. The intervention group of the RCTs gets support by personal navigators for 12 months. The control group receives a brochure with regional support offers for patients and caregivers. The feasibility of the patient-oriented navigation model for two prototypic age-associated diseases, lung cancer and stroke, is evaluated with regard to its acceptance, demand, practicality and efficacy. This investigation includes process evaluation measures with detailed documentation of the screening and recruitment process, questionnaires about satisfaction with navigation, observant participation and qualitative interviews. Estimates of efficacy for patient-reported outcomes are obtained at three follow-up time points including satisfaction with care and health-related quality of life. Furthermore, we analyze health insurance data from patients of the RCT insured at a large German health insurance (AOK Nordost) to investigate heath care utilization, costs and cost effectiveness. TRIAL REGISTRATION: The study is registered at the German Clinical Trial Register (DRKS-ID: DRKS00025476).

Classification of Intracranial Stenoses: Discrepancies between Transcranial Duplex Sonography and Computed Tomography Angiography.

Transcranial color-coded duplex sonography (TCCS) and computed tomography angiography (CTA) are widely used to identify intracranial stenoses (ISs). We assessed concordance of IS grading between TCCS and CTA and proposed new TCCS criteria for severe IS ≥70%. One hundred two stroke patients (70 ± 13 y) with TCCS-identified IS were included. TCCS and CTA were performed within 24 h after admission. TCCS peak systolic velocity cutoffs for <50%/50%-69% stenoses were ≥155/≥220 cm/s (middle cerebral artery [MCA]-M1), ≥100/≥140 cm/s (MCA-M2), ≥120/≥155 cm/s (anterior cerebral artery [ACA]-A1), ≥100/≥145 cm/s (posterior cerebral artery [PCA]-P1 and PCA-P2), ≥90/≥120 cm/s (vertebral artery [VA]-V4) and ≥100/≥140 cm/s (basilar artery [BA]). Criteria for ≥70% stenoses were, despite variable flow velocities, post-stenotic flow alterations and/or leptomeningeal collateral flow. One hundred seventy-seven ISs were detected by TCCS. The number and grade (<50%/50%-69%/≥70%) of ISs were MCA 70 (39/19/12), BA 24 (9/11/4), ACA 21 (14/7/0), PCA 49 (29/15/5) and VA 13 (2/6/5). IS localization was confirmed by CTA in 84 of 177 cases (48%): MCA, 41/70 (59%); BA, 16/24 (67%); ACA 2/21, (10%); PCA, 17/49 (35%); VA, 8/13 (62%). Concordance between TCCS and CTA grading was (<50%/50%-69%/≥70%) 17%/19%/77%. TCCS and CTA exhibited substantial differences in the detection and grading of IS. Higher concordance rates for severe stenosis support our proposed TCCS criteria.

Pattern of Activated Pathways and Quality of Collateral Status in Patients with Symptomatic Internal Carotid Artery Occlusion.

BACKGROUND: Internal carotid artery occlusion (ICAO) is an important risk factor for stroke. Cerebral hemodynamics in patients with ICAO depends on the individual capacity to activate sufficient collateral pathways. Therefore, the assessment of intracranial collaterals is essential for the acute and long-term management of these patients and accurate estimation of further stroke risk. METHODS: Acute stroke patients with unilateral ICAO were prospectively enrolled. We assessed the following collaterals by transcranial color-coded sonography (TCCS): the anterior and posterior communicating artery (ACoA, PCoA), the ophthalmic artery (OA), and leptomeningeal collaterals of the posterior cerebral artery (LMC). We subdivided the flow pattern of the Doppler spectrum in the middle cerebral artery (MCA) into 3 categories: (1) good, (2) moderate, and (3) bad according to the hemodynamic effects on the ipsilateral MCA flow. Finally, we compared the individual TCCS results with the stroke pattern detected on CT or MRI scan. RESULTS: One hundred thirteen patients (age 66 ± 12 years; -female 24) were included. The collateral status was good, moderate, and bad in 59 (52%), 37 (33%), and 17 (15%) patients, respectively. The ACoA collateral was most frequently activated (81%), followed by the OA (63%), the PCoA (53%), and the LMC (22%). The quality of the collateral status was determined by the type (p = 0.0003) but not by the number (p = 0.19) of activated collateral pathways. Good collateral function was highly associated with primary collaterals (ACoA > PCoA). Best parameter for a good collateral status was an antegrade flow in the OA, indicating a high blood supply via the communicating arteries. CONCLUSIONS: TCCS allows the assessment of intracranial collaterals and their hemodynamic capacity. Prevalence of collateral sufficiency in ICAO seems to be higher than previously reported. ACoA cross flow is essential for the optimal hemodynamic compensation of ICAO. Antegrade OA flow indicates good collateral status.

Emergency Room Use of "Fast-Track" Ultrasound in Acute Stroke: An Observational Study.

Early information on vascular status in acute stroke is essential. We analyzed whether duplex ultrasound (DUS) using a fast-track protocol provides this information without relevant delay. One hundred forty-six patients were prospectively enrolled. DUS was performed by sonographers with two levels of experience. The carotid and vertebral arteries, as well as all basal cerebral arteries, were bilaterally analyzed. Criteria for vessel analysis were (i) normal or stenosis <50%, (ii) stenosis ≥50% and (iii) occlusion. The mean duration of the ultrasound investigation was 6:07 ± 2:06 min with a significant difference between more and less experienced investigators (p < 0.0001). Insonation times decreased during the study in both groups. The sensitivity, specificity, positive predictive value and negative predictive value of ultrasound findings in comparison with computed tomography angiography were 73%, 99%, 84% and 98%, respectively. Our data suggest that "fast track" DUS is feasible and reliable. The time required for DUS assessment depends on the sonographer´s experience.

Delirium is associated with frequency band specific dysconnectivity in intrinsic connectivity networks: preliminary evidence from a large retrospective pilot case-control study.

BACKGROUND: Pathophysiological concepts in delirium are not sufficient to define objective biomarkers suited to improve clinical approaches. Advances in neuroimaging have revalued electroencephalography (EEG) as a tool to assess oscillatory network activity in neuropsychiatric disease. Yet, research in the field is limited to small populations and largely confined to postoperative delirium, which impedes generalizability of findings and planning of prospective studies in other populations. This study aimed to assess effect sizes of connectivity measures in a large mixed population to demonstrate that there are measurable EEG differences between delirium and control patients. METHODS: This retrospective pilot study investigated EEG measures as biomarkers in delirium using a case-control design including patients diagnosed with delirium (DSM-5 criteria) and age-/gender-matched controls drawn from a database of 9980 patients (n = 129 and 414, respectively). Assessors were not blinded for groups. Power spectra and connectivity estimates, using the weighted phase log index, of continuous EEG data were compared between conditions. Alterations of information flow through nodes of intrinsic connectivity networks (ICN; default mode, salience, and executive control network) were evaluated in source space using betweenness centrality. This was done frequency specific and network nodes were defined by the multimodal human cerebral cortex parcellation based on human connectome project data. RESULTS: Delirium and control patients exhibited distinct EEG power, connectivity, and network characteristics (F (72,540) = 70.3, p < .001; F (493,1079) = 2.69, p < .001; and F (718,2159) = 1.14, p = .007, respectively). Connectivity analyses revealed global alpha and regional beta band disconnectivity that was accompanied by theta band hyperconnectivity in delirious patients. Source and network analyses yielded that these changes are not specific to single intrinsic connectivity networks but affect multiple nodes of networks engaged in level of consciousness, attention, working memory, executive control, and salience detection. Effect sizes were medium to strong in this mixed population of delirious patients. CONCLUSIONS: We quantified effect sizes for EEG connectivity and network analyses to be expected in delirium. This study implicates that theta band hyperconnectivity and alpha band disconnectivity may be essential mechanisms in the pathophysiology of delirium. Upcoming prospective studies will build upon these results and evaluate the clinical utility of identified EEG measures as therapeutic and prognostic biomarkers.

Diagnostic Performance and Utility of Quantitative EEG Analyses in Delirium: Confirmatory Results From a Large Retrospective Case-Control Study.

Background. The lack of objective disease markers is a major cause of misdiagnosis and nonstandardized approaches in delirium. Recent studies conducted in well-selected patients and confined study environments suggest that quantitative electroencephalography (qEEG) can provide such markers. We hypothesize that qEEG helps remedy diagnostic uncertainty not only in well-defined study cohorts but also in a heterogeneous hospital population. Methods. In this retrospective case-control study, EEG power spectra of delirious patients and age-/gender-matched controls (n = 31 and n = 345, respectively) were fitted in a linear model to test their performance as binary classifiers. We subsequently evaluated the diagnostic performance of the best classifiers in control samples with normal EEGs (n = 534) and real-world samples including pathologic findings (n = 4294). Test reliability was estimated through split-half analyses. Results. We found that the combination of spectral power at F3-P4 at 2 Hz (area under the curve [AUC] = .994) and C3-O1 at 19 Hz (AUC = .993) provided a sensitivity of 100% and a specificity of 99% to identify delirious patients among normal controls. These classifiers also yielded a false positive rate as low as 5% and increased the pretest probability of being delirious by 57% in an unselected real-world sample. Split-half reliabilities were .98 and .99, respectively. Conclusion. This retrospective study yielded preliminary evidence that qEEG provides excellent diagnostic performance to identify delirious patients even outside confined study environments. It furthermore revealed reduced beta power as a novel specific finding in delirium and that a normal EEG excludes delirium. Prospective studies including parameters of pretest probability and delirium severity are required to elaborate on these promising findings.

Assessment of intracranial venous blood flow after subarachnoid hemorrhage: a new approach to diagnose vasospasm with transcranial color-coded duplex sonography.

OBJECTIVETranscranial color-coded duplex sonography (TCCS) is a reliable tool that is used to assess vasospasm in the M1 segment of the middle cerebral artery (MCA) after subarachnoid hemorrhage (SAH). A distinct increase in blood flow velocity (BFV) is the principal criterion for vasospasm. The MCA/internal carotid artery (ICA) index (Lindegaard Index) is also widely used to distinguish between vasospasm and cerebral hyperperfusion. However, extracranial ultrasonography assessment of the neck vessels might be difficult in an intensive care unit. Therefore, the authors evaluated whether the relationship of intracranial arterial to venous BFV might indicate vasospasm with similar or even better accuracy.METHODSPatients who presented between 2008 and 2015 with aneurysmal SAH were prospectively enrolled in the study. Digital subtraction angiography (DSA) and TCCS were performed within 24 hours of each other to assess vasospasm 8-10 days after SAH. The following different TCCS parameters were analyzed to assess vasospasm in the MCA and were compared with the gold-standard DSA parameters: 1) mean time-averaged maximum BFV (Vmean) of the MCA, 2) peak systolic velocity (PSV) of the MCA, 3) the Lindegaard Index using Vmean as well as PSV, and 4) a new arteriovenous index (AVI) between the MCA and the basal vein of Rosenthal using Vmean and PSV. The best cutoff values for these parameters to distinguish vasospasm from normal perfusion or hyperperfusion were calculated using receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, and negative predictive value as well as the overall accuracy for each cutoff value were analyzed.RESULTSA total of 102 patients (mean age 52 ± 12 years) were evaluated. Bilateral MCA assessment by TCCS was successful in all patients. In 6 cases (3%), the BFV of the basal vein of Rosenthal could not be analyzed. The AVI could not be calculated in 50 of 204 cases (25%) because the insonation quality was very low in one of the ICAs. An AVI > 10 for Vmean and an AVI > 12 for systolic velocity provided the highest accuracies of 87% and 86%, respectively. Regarding the Lindegaard Index, the accuracy was highest using a threshold of > 3 for the mean BFV (84%) as well as systolic BFV (80%). BFVs in the MCA of ≥ 120 cm/sec (Vmean) and ≥ 200 cm/sec (PSV) predicted vasospasm with accuracies of 84% and 83%, respectively. A combined analysis of the MCA BFV and the AVI led to a slight increase in specificity (Vmean, 94%; PSV, 93%) and positive predictive value (Vmean, 88%; PSV 86%) without further improvement in accuracy (Vmean, 88%; PSV, 84%).CONCLUSIONSThe intracranial AVI is a reliable parameter that can be used to assess vasospasm after SAH. Its reliability for differentiating vasospasm and hyperperfusion is slightly higher than that for the established Lindegaard Index, and this method has the additional advantage of a remarkably lower failure rate.

B-mode ultrasound assessment of pupillary function: Feasibility, reliability and normal values.

PURPOSE: To evaluate B-mode ultrasound as a novel method for the examination of pupillary function and to provide normal values for the pupillary reflex as assessed by B-mode ultrasound. METHODS: 100 subjects (49 female, 51 male, mean [range] age 51 [18-80 years]) with no history of ophthalmologic disease, no clinically detectable pupillary defects, and corrected visual acuity ≥ 0.8 were included in this prospective observational study. B-mode ultrasound was performed with the subjects eyes closed using an Esaote-Mylab25 system according to current guidelines for orbital insonation. A standardized light stimulus was applied. RESULTS: The mean ± standard deviation left and right pupillary diameters (PD) at rest were 4.7 ± 0.8 and 4.5 ± 0.8 mm. Following an ipsilateral light stimulus (Lstim), left and right constricted PD were 2.8 ± 0.6 and 2.7 ± 0.6 mm. Following a contralateral Lstim, left and right constricted PD were 2.7 ± 0.6 and 2.6 ± 0.5 mm. Left and right pupillary constriction time (PCT) following ipsilateral Lstim were 970 ± 261.6 and 967 ± 220 ms. Left and right PCT following a contralateral Lstim were 993.8 ± 192.6 and 963 ± 189.4 ms. Patient age was inversely correlated with PD at rest and with PD after ipsilateral and contralateral Lstim (all p<0.001), but not with PCT. CONCLUSIONS: B-mode ultrasound is a simple, rapid and objective method for the quantitative assessment of pupillary function, which may prove useful in a variety of settings where eyelid retraction is impeded or an infrared pupillometry device is unavailable.

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.

No Evidence for Retinal Damage Evolving from Reduced Retinal Blood Flow in Carotid Artery Disease.

INTRODUCTION: Carotid artery disease (CAD) comprising high-grade internal carotid artery stenosis (CAS) or carotid artery occlusion (CAO) may lead to ipsilateral impaired cerebral blood flow and reduced retinal blood supply. OBJECTIVE: To examine the influence of chronic CAD on retinal blood flow, retinal morphology, and visual function. METHODS: Patients with unilateral CAS ≥ 50% (ECST criteria) or CAO were grouped according to the grade of the stenosis and to the flow direction of the ophthalmic artery (OA). Retinal perfusion was measured by transorbital duplex ultrasound, assessing central retinal artery (CRA) blood flow velocities. In addition, optic nerve and optic nerve sheath diameter were measured. Optical coherence tomography (OCT) was performed to study retinal morphology. Visual function was assessed using high- and low-contrast visual paradigms. RESULTS: Twenty-seven patients were enrolled. Eyes with CAS ≥ 80%/CAO and retrograde OA blood flow showed a significant reduction in CRA peak systolic velocity (no-CAD side: 0.130 ± 0.035 m/s, CAS/CAO side: 0.098 ± 0.028; p = 0.005; n = 12). OCT, optic nerve thicknesses, and visual functional parameters did not show a significant difference. CONCLUSION: Despite assessable hemodynamic effects, chronic high-grade CAD does not lead to gaugeable morphological or functional changes of the retina.

Triglycerides and carotid intima-media thickness in ischemic stroke patients.

BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. METHODS: All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charité Virchow and Charité Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3-7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism-namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). RESULTS: We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. CONCLUSION: Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. CLINICAL TRIAL REGISTRATION INFORMATION: The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and clinicaltrials.gov (NCT 01378468).

Delayed Transcranial Echo-Contrast Bolus Arrival in Unilateral Internal Carotid Artery Stenosis and Occlusion.

Some patients with internal carotid artery (ICA) occlusion or stenosis are at risk of developing a hemodynamic stroke. Transcranial ultrasonography using an echo-contrast bolus technique might be able to assess the extent of hemodynamic compromise. We describe a transcranial Doppler sonographic method that analyzes the differences in echo-contrast bolus arrival between both middle cerebral arteries after intravenous echo-contrast application. Ten patients with 50%-79% ICA stenosis, 10 patients with 80%-99% ICA stenosis and 22 patients with ICA occlusion were studied and compared with 15 age-matched controls. There were significant increases in delayed filling of the middle cerebral artery in both 80%-99% stenoses and occlusions compared with controls. The extent of the observed delays did not correlate with vasomotor reactivity. Echo-contrast bolus arrival time can be used to gain additional information on the intracranial hemodynamic effects of extracranial carotid artery disease that seems to be independent of the established ultrasound indices.

Effect of fingolimod (FTY720) on cerebral blood flow, platelet function and macular thickness in healthy volunteers.

AIM: Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers. METHODS: The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value). RESULTS: All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports. CONCLUSIONS: In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.

Cortical reorganization due to impaired cerebral autoregulation in individuals with occlusive processes of the internal carotid artery.

BACKGROUND AND PURPOSE: To study the impact of impaired cerebral autoregulation on cortical neurophysiology, long term potentiation (LTP)-like plasticity, motor learning and brain structure. METHODS: 12 patients with unilateral occlusion or severe stenosis of the internal carotid artery were included. Impairment of cerebral autoregulation was determined by vasomotor reactivity in transcranial Doppler sonography. Corticomotor excitability, cortical silent period and LTP-like plasticity were assessed with transcranial magnetic stimulation, motor learning with a force production task, and brain structure with high-resolution MRI of the brain. RESULTS: In the affected hemisphere, corticomotor excitability was significantly higher, cortical silent period and LTP-like plasticity significantly lower, compared to the contralateral side. No significant difference emerged for motor learning, cortical thickness and white matter integrity between the hemispheres. CONCLUSION: Despite decreased LTP-like plasticity in the affected hemisphere, motor learning was comparable between hemispheres, possibly due to gamma-aminobutyric-acid (GABA)B-mediated corticomotor excitability changes within the affected hemisphere. Our results may help to develop interventions to beneficially modulate cortical physiology in the presence of cerebral hypoperfusion.

Duplex sonography of cerebral blood flow after cardiac arrest--a prospective observational study.

AIM: Despite successful resuscitation, cardiac arrest (CA) often has a poor clinical prognosis. Different diagnostic tools have been established to predict patients' outcome. However, their sensitivity remains low. Assessment of cerebral perfusion by duplex ultrasound might provide additional information regarding the extent of neuronal damage. The aim of the present study was to analyse the changes of global cerebral blood flow (CBF) and intracranial blood flow parameters in the acute stage after CA and its correlation with patients' outcome. METHODS: We investigated 54 patients (17-85 years, mean age: 63±17 years) after CA with return of spontaneous circulation on an intensive care unit. All patients received therapeutic hypothermia (TH) for 24 h after CA and reanimation. Serial measurements of CBF as well as intracranial blood flow velocities and pulsatility indices of the middle cerebral artery and the basal vein of Rosenthal were performed within the first 10 days using duplex ultrasound. Clinical outcome was measured using the Cerebral Performance Category. RESULTS: Measurements were successful in 53 patients. CBF values differed between 210 and 1100 ml/min. 24 patients (45%) attained a good outcome. No correlation between CBF or intracranial blood flow characteristics and outcome was found. Neither cerebral hypo- nor hyperperfusion was associated with a fatal outcome. CONCLUSION: Cerebral perfusion varies widely after CA. Neither hypo- nor hyperperfusion seems to be an independent risk factor for poor outcome. Duplex ultrasound of cerebral haemodynamics after CA is suitable but probably of limited prognostic value.

Long-chain omega-3 fatty acids improve brain function and structure in older adults.

Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.

Transcranial ultrasound analysis of cerebral blood flow during induced hypertension in acute ischemic stroke - a case series.

BACKGROUND: Current recommendations of stroke treatment favour a moderately elevated blood pressure in the acute phase, based on the concept of an improved cerebral perfusion. Here, cerebral blood flow was assessed in a case series of patients with acute hemodynamic stroke by means of transcranial colour-coded sonography (TCCS) to study the effects of pharmacologically induced hypertension. FINDINGS: We investigated six patients with acute hemodynamic stroke and blood pressure-dependent clinical fluctuation of neurological symptoms. TCCS was performed during the initiation phase of catecholamine-induced controlled hypertension. A blood pressure-dependent increase of flow velocity in the ipsilesional middle and the posterior cerebral artery was found in all patients (mean increase 0.80% and 0.65% per mmHg, respectively). CONCLUSIONS: Catecholamine-induced hypertension in severe hemodynamic stroke leads to an ultrasound-detectable rise of cerebral blood flow. This finding gives 'proof-of-principle' evidence, supporting active blood pressure management in this selected group of stroke patients. Outcome-related questions of target blood pressure, treatment duration or applicability to other forms of stroke, however, remain to be studied. In this, transcranial ultrasound may be a valuable tool for patient selection and subsequent bedside monitoring.