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Mapping flows in vivo is essential for the investigation of cardiovascular pathologies in animal models. The limitation of optical-based methods, such as space-time cross correlation, is the scattering of light by the connective and fat components and the direct wave front distortion by large inhomogeneities in the tissue. Nonlinear excitation of the sample fluorescence helps us by reducing light scattering in excitation. However, there is still a limitation on the signal-background due to the wave front distortion. We develop a diffractive optical microscope based on a single spatial light modulator (SLM) with no movable parts. We combine the correction of wave front distortions to the cross-correlation analysis of the flow dynamics. We use the SLM to shine arbitrary patterns of spots on the sample, to correct their optical aberrations, to shift the aberration corrected spot array on the sample for the collection of fluorescence images, and to measure flow velocities from the cross-correlation functions computed between couples of spots. The setup and the algorithms are tested on various microfluidic devices. By applying the adaptive optics correction algorithm, it is possible to increase up to 5 times the signal-to-background ratio and to reduce approximately of the same ratio the uncertainty of the flow speed measurement. By working on grids of spots, we can correct different aberrations in different portions of the field of view, a feature that allows for anisoplanatic aberrations correction. Finally, being more efficient in the excitation, we increase the accuracy of the speed measurement by employing a larger number of spots in the grid despite the fact that the two-photon excitation efficiency scales as the fourth power of this number: we achieve a twofold decrease of the uncertainty and a threefold increase of the accuracy in the evaluation of the flow speed.

Current arterial pulse monitoring systems capture data at high frequencies (100–1000 Hz). However, they typically report averaged or low frequency summary data such as heart rate and systolic, mean and diastolic blood pressure. In doing so, a potential wealth of information contained in the high-fidelity waveform data is discarded, data which has long been known to contain useful information on cardiovascular performance. Here we summarise a new mathematical method, attractor reconstruction, which enables the quantification of arterial waveform shape and variability in real-time. The method can handle long streams of non-stationary data and does not require preprocessing of the raw physiological data by the end user. Whilst the detailed mathematical proofs have been described elsewhere (Aston et al 2008 Physiol. Meas. 39), the authors were motivated to write a summary of the method and its potential utility for biomedical researchers, physiologists and clinician readers. Here we illustrate how this new method may supplement and potentially enhance the sensitivity of detecting cardiovascular disturbances, to aid with biomedical research and clinical decision making.

BACKGROUND: Cognitive improvement has been reported in patients receiving centrally acting angiotensin-converting enzyme inhibitors (C-ACEIs). AIMS: To compare cognitive decline and survival after diagnosis of Alzheimer's disease between people receiving C-ACEIs, non-centrally acting angiotensin-converting enzyme inhibitors (NC-ACEIs), and neither. METHOD: Routine Mini-Mental State Examination (MMSE) scores were extracted in 5260 patients receiving acetylcholinesterase inhibitors and analysed against C-/NC-ACEI exposure at the time of Alzheimer's disease diagnosis. RESULTS: In the 9 months after Alzheimer's disease diagnosis, MMSE scores significantly increased by 0.72 and 0.19 points per year in patients on C-ACEIs and neither respectively, but deteriorated by 0.61 points per year in those on NC-ACEIs. There were no significant group differences in score trajectories from 9 to 36 months and no differences in survival. CONCLUSIONS: In people with Alzheimer's disease receiving acetylcholinesterase inhibitors, those also taking C-ACEIs had stronger initial improvement in cognitive function, but there was no evidence of longer-lasting influence on dementia progression. DECLARATION OF INTEREST: R.S. has received research funding from Pfizer, Lundbeck, Roche, Janssen and GlaxoSmithKline. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Background: Previous studies of prognosis after a transient ischaemic attack (TIA) have recruited patients soon after the event, when the risk of stroke is very high. However, the majority of patients survive for many years after a TIA, and the need for continued preventive treatment to lower vascular risk will need to be reassessed at a later date. Obective: To determine the long term risks of stroke and other vascular events in patients with TIA who survive the initial high risk period. Methods: 290 patients were studied who had initially been followed up after a TIA in the Oxford community stroke project and in a contemporaneous hospital based cohort study, and who were alive and stroke-free at the end of planned follow up in 1988. All patients were followed for a further 10 years, and the risks of major vascular events (stroke, myocardial infarction, vascular death) were determined. Standardised mortality ratios (SMR) were calculated from the observed numbers of fatal events and the number expected on the basis of age and sex in the general population. Results: Median time since last TIA was 3.8 years (interquartile range, 2.2 to 5.8 years). The risk of major vascular events was constant through time. The 10 year risk of first stroke was 18.8% (95% confidence interval (CI), 13.6 to 23.7; 45 events). The 10 year risk of myocardial infarction or death from coronary heart disease was 27.8% (95% CI, 21.8 to 33.3; 67 events) and there was a significant excess of fatal coronary events compared with that expected in the general population (SMR = 1.47; 95% CI, 1.10 to 1.93; p = 0.009). A total of 114 patients had at least one major vascular event, with a 10 year risk of any first stroke, myocardial infarction, or vascular death of 42.8% (95% CI, 36.4 to 48.5). Conclusions: The overall risk of major vascular events remains high for 10 to 15 years after a TIA. It is important therefore that preventive treatments are continued in the long term, even in apparently "low risk" patients who have already survived free of stroke for several years.

Recent observations suggest that the adventitial layer of blood vessels exhibits properties resembling a stem/progenitor cell niche. Progenitor cells have been isolated from the adventitia of both murine and human blood vessels with the potential to form endothelial cells, mural cells, osteogenic cells, and adipocytes. These progenitors appear to cluster at or near the border zone between the outer media and inner adventitia. In the mouse, this border zone region corresponds to a localized site of sonic hedgehog signaling in the artery wall. This brief review will discuss the emerging evidence that the tunica adventitia may provide a niche-like signaling environment for resident progenitor cells and will address the role of the adventitia in growth, remodeling, and repair of the artery wall.

Objective: To report the nature of stroke in patients infected with human immunodeficiency virus (HIV) in a region with high HIV seroprevalence and describe HIV associated vasculopathy. Methods: Patients with first ever stroke, infected with HIV and prospectively included in the stroke register of the Groote Schuur Hospital/University of Cape Town stroke unit were identified and reviewed. Results: Between 2000 and 2006, 67 of the 1087 (6,1%) stroke patients were HIV infected. Of these, 91% (n = 61) were younger than 46 years. Cerebral infarction occurred in 96% (n = 64) of the HIV positive patients and intracerebral haemorrhage in 4% (n = 3). HIV infected young stroke patients did not demonstrate hypertension, diabetes, hyperlipidaemia or smoking as significant risk factors for ischaemic stroke. Infection as a risk factor for stroke was significantly more common in HIV positive patients (p = 0.018, OR 6.4, CI 3.1 to 13.2). In 52 (81%) patients with ischaemic stroke, an aetiology was determined. Primary aetiologies comprised infectious meningitides/vasculitides in 18 (28%) patients, coagulopathy in 12 (19%) patients and cardioembolism in nine (14%) patients. Multiple aetiologies were present in seven (11%) patients with ischaemic stroke. HIV associated vasculopathy was identified in 13 (20%) patients. The HIV associated vasculopathy manifested either extracranially (seven patients) as total or significant carotid occlusion or intracranially (six patients) as medium vessel occlusion, with or without fusiform aneurysmal dilation, stenosis and vessel calibre variation. Conclusion: Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients. In our cohort, 20% of patients demonstrated evidence of an HIV associated vasculopathy.

Objective: To determine whether central periodic breathing (CPB) is associated with acute involvement of any particular part of the brain, or the extent of total damage in patients with acute stroke. Methods: CPB was identified using portable monitoring equipment in patients with stroke on admission. A neuroradiologist classified acute stroke lesions and prior cerebrovascular disease on brain images. Results: Among 134 patients with acute stroke, those with CPB were more likely to have a large acute stroke lesion in a cerebral hemisphere (p = 0.01) and more mass effect (p = 0.03). There was no association between CPB and severe prior cerebrovascular disease on imaging (p = 0.76). Conclusion: CPB is related to the acute (not old) lesions, particularly large acute cerebral hemispheric lesions with mass effect. A relationship between lesions in any discrete brain location (unilateral or bilateral) and CPB could not be shown.

Background and aims: An important part is played by inflammation in intracranial aneurysm formation. The hypothesis that there is an association of the proinflammatory cytokine interleukin-6 (IL-6) genotypes (−572G>C and −174G>C) with intracranial aneurysms was tested. Methods: IL-6 genotypes were determined in 91 Caucasian patients with aneurysms and compared with 2720 healthy UK controls. Results: For both polymorphisms, the distribution of the genotypes and estimated allele frequency were different between the control group and the aneurysm group. For −572G>C, a higher frequency of the C allele (p = 0.001) and more people homozygous for the C allele were found among those with aneurysms than among the controls (4.4% v 0.3%, p = 0.001). For −174G>C, more people homozygous for the C allele were found among the controls than among those with aneurysm (18% v 7%, p = 0.007). The 572C/174G haplotype was associated with an increased risk of aneurysms, with the relative risk compared with the common haplotype being 1.89 and that for the −572G/174C haplotype being 0.58 (p Conclusion: This is the first study to show that IL-6 promoter polymorphisms are associated with intracranial aneurysmal disease. Whether this association is with the development, progression or rupture of such aneurysms, or represents survivor bias, is unclear.

Background: Retinal infarction and transient monocular blindness (TMB) are associated with an increased risk of future ischaemic stroke. Little information is available on the type of subsequent ischaemic strokes that may occur (anterior or posterior circulation and small vessel or large vessel). Aim: To analyse the type of stroke after TMB. Methods: Patients with transient or permanent retinal ischaemia were selected from three prospective studies: the Dutch TIA Trial, the Dutch Amaurosis Fugax Study and the European/Australian Stroke Prevention in Reversible Ischaemia Trial. On follow-up the type of stroke was classified according to the supply territory and the type of vessel involved. Results: 654 patients were included. During a mean follow-up of 5.2 years, 42 patients were found to have had a cerebral or retinal infarct, of which 27 occurred in the carotid territory ipsilateral to the symptomatic eye, 9 in the territory of the contralateral carotid artery and 6 were infratentorial strokes. Thirty patients had a large-vessel infarct, four had a small-vessel infarct and eight had a retinal infarct. Characteristics associated with a notable increased risk for subsequent stroke or retinal infarction were age ⩾65 years, a history of stroke, a history of intermittent claudication, diabetes mellitus, Rankin score ⩾3, more than three attacks of retinal ischaemia and any degree of ipsilateral carotid stenosis on duplex ultrasonography observation. Conclusion: Ischaemic strokes after TMB or retinal infarction were found to be mainly large-vessel infarcts in the territory of the ipsilateral carotid artery. TMB and retinal infarction are probably manifestations of large-vessel disease.

Background: Spontaneous intracerebral haemorrhage (ICH) accounts for the highest in-hospital mortality of all stroke types. Nevertheless, outcome is favourable in about 30% of patients. Only one model for the prediction of favourable outcome has been validated so far. Objective: To describe the development and validation of the Essen ICH score. Methods: Inception cohorts were assessed on the National Institutes of Health stroke scale (NIH-SS) on admission and after follow up of 1 CX) days. On the basis of previously validated clinical variables, a simple clinical score was developed to predict mortality and complete recovery (Barthel index after 100 days ≥95) in 340 patients with acute ICH. Subscores for age (20 or coma = 4) were combined into a prognostic scale with 7 predicting death. The score was subsequently validated in an external cohort of 371 patients. Results: The Essen ICH score showed a high prognostic accuracy for complete recovery and death in both the development and validation cohort. For prediction of complete recovery on the Barthel index after 100 days, the Essen ICH score was superior to the physicians' prognosis and to two previous prognostic scores developed for a slightly modified outcome. Conclusions: The Essen ICH score provides an easy to use scale for outcome prediction following ICH. Its high positive predictive values for adverse outcomes and easy applicability render it useful for individual prognostic indications or the design of clinical studies. In contrast, physicians tended to predict outcome too pessimistically.

BackgroundRodent models of acute ischaemic stroke and head injury suggest that apolipoprotein E (APOE) genotype influences neuronal repair, regeneration and survival after brain injury. Possession of an APOE ε4 allele is associated with poor outcome after head injury in clinical studies. APOE might therefore influence outcome after acute stroke in humans.Objective and methodsTo comprehensively search, identify, assess and carry out meta‐analyses of studies reporting on the association between APOE and the combined outcome of death or dependency, or death alone, several months after ischaemic stroke, intracerebral haemorrhage (ICH) or subarachnoid haemorrhage (SAH).ResultsMain analyses included data from nine studies on 2262 patients (1453 with ischaemic stroke, 199 with ICH and 610 with SAH). Overall, ε4+ genotypes were not significantly associated with risk of death or dependency several months after stroke. However, there was significant heterogeneity between studies, and between the three pathological types of stroke. ε4+ genotypes were associated with increased death or dependency after SAH (relative risk (RR) 1.40, 95% confidence interval (CI) 1.06 to 1.84), with a trend towards a similar association with ICH (RR 1.38, 95% CI 0.99 to 1.92), but not with ischaemic stroke (RR 0.98, 95% CI 0.85 to 1.12). Results were similar for death alone.ConclusionsAPOE may differentially affect outcome after the three main pathological types of stroke. Further, large studies are needed to confirm or refute these findings, and to assess the possibility of an interaction between the effects of APOE and age.In contrast with the many studies assessing the role of various candidate genes in the causation of stroke and its subtypes,1,2,3 the role of genetic factors influencing outcome after acute stroke has been relatively little studied in humans.4,5 However, studies on animal models of stroke comparing outcomes among genetically manipulated animals with those among wild‐type animals suggest that this should be a promising subject, which may ultimately improve our understanding of the pathways of neuronal protection and recovery, and even lead to new therapeutic insights.4,6The apolipoprotein E gene (APOE) is one of the most widely studied genes in vascular and neurodegenerative diseases. Its protein product is a 34‐kDa glycoprotein with three common isoforms, E2, E3 and E4, encoded by the alleles ε2, ε3 and ε4, respectively, giving rise to six genotypes, the ε3/ε3 genotype occurring in about 50–66% of people in most populations.7 APOE has a major role in lipid redistribution, which is important for membrane maintenance and repair in the brain, and in the regulation of synaptic remodelling during or after brain injury.6,8,9,10,11 Rodent models of head injury and ischaemic stroke suggest that APOE influences neuronal repair, regeneration and survival after brain injury.6,11 In clinical studies, possession of an APOE ε4 allele is associated with poor outcome after head injury.5 These observations suggest that APOE might influence outcome after acute stroke in humans, but clinical studies have produced conflicting results.5Here, we use systematic review and meta‐analysis methods to assess the effect of APOE on outcome after the three main pathological types of acute stroke: ischaemic stroke, intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH).

Objectives: To determine the long term survival and predictors of death in patients with primary intracerebral haemorrhage (ICH) in Central Finland. Methods: Data were collected retrospectively on all adult patients with first ever ICH in Central Finland county between September 1985 and December 1991. The survival of all patients at the end of December 2002 was investigated. Kaplan–Meier survival curves were constructed and factors associated with both early (⩽28 days) and late deaths determined. Long term survival was compared with the general Finnish population of the same age and sex distribution. The causes of death were compared with those of the population of Central Finland. Results: 411 patients with first ever ICH were identified, 199 men (mean age 64.9 years) and 212 women (mean age 69.5); 30 died before hospital admission, and 208 (50.6%) within the first 28 days. In Kaplan–Meier analysis, at 16 years the cumulative survival was 3.2% for men and 9.8% for women. The 28 day survivors had a 4.5-fold increased annual risk of dying during the first year after ICH, and 2.2-fold during years 2 to 6. On admission, significant independent predictors of death within the first four weeks were unconsciousness, lateral shift of cerebral midline structures, mean arterial pressure ⩾134 mm Hg, hyperglycaemia, anticoagulant treatment, and ventricular extrasystoles. Predictors of late death for the 28 day survivors were old age, male sex, and heart failure. Conclusions: Primary intracerebral haemorrhage has a poor short and long term outcome. The results emphasise the importance of primary and secondary prevention for ICH.

BACKGROUND AND OBJECTIVES: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. METHODS: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. RESULTS: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p

Different grading systems of arterial recanalisation have never been compared in large series of stroke patients treated with intra-arterial thrombolysis (IAT).Clinical and angiographic findings and outcome were analysed in 147 patients with M1 or M2 segment occlusion of the middle cerebral artery treated with IAT. Associations of the thrombolysis in myocardial infarction (TIMI) grading system and the Mori grading system with clinical outcome were compared.The median NIHSS score on admission was 15 and the mean time from symptom onset to IAT was 242 minutes. After three months the outcome was favourable (defined as modified Rankin scale score (mRS)or = 2) in 85 patients (58%) and poor (mRS 3 to 5) in 44 (30%); 18 patients (12%) were dead. Recanalisation was categorised as TIMI grade 0 in 17 patients (12%), TIMI 1 in 16 (11%), TIMI 2 in 83 (56%), and TIMI 3 in 31(21%). Seventeen patients (12%) showed Mori grade 0 reperfusion, 16 (11%) Mori 1, 37 (25%) Mori 2, 46 (31%) Mori 3, and 31 (21%) Mori 4. In both TIMI and Mori grading systems, reopening the artery was an independent predictor of a favourable clinical outcome (p0.0001). When recanalisation was partial, outcome was better in patients with reperfusion50% (Mori 3) than in those with reperfusion50% (Mori 2) (p = 0.008).Both TIMI and Mori grading systems are useful for predicting outcome after stroke and IAT. When recanalisation is partial the Mori classification is more refined in giving prognostic information.

Background: Apart from diffusion-weighted imaging (DWI) lesion volume and diffusion–perfusion mismatching, there is limited information about neuroradiological predictors of early prognosis after an ischaemic stroke. This study sought to identify specific DWI lesion patterns that would help prediction of early prognosis of three different endpoints: unstable hospital course, recurrence of stroke, and poor neurological outcome at 90 days after ischaemic stroke. Methods: A total of 426 patients with acute cerebral infarcts within the middle cerebral artery territory were prospectively studied. Using the DWI data the patients were divided into six groups (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts), and any recurrent strokes and prognosis over the following 90 days were recorded. Results: DWI lesion pattern was a stronger and more consistent independent outcome predictor than DWI lesion volume. The specific DWI lesion patterns associated with each endpoint differed. An unstable hospital course was frequently observed in patients with internal border zone infarcts, whereas recurrent strokes after the index stroke were commoner in those who had small superficial infarcts (p Conclusions: The results of the present study indicate that the DWI lesion pattern may help in recognition of the likely differences in the early prognostic endpoints after ischaemic stroke, and DWI analysis may guide targeted interventions to prevent negative outcomes.

The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance.To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter.A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate.When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage.Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

Background: The apparent differences in risk factors for intra- and extracranial atherosclerosis are unclear and the mechanisms that underlie strokes in patients with intracranial atherosclerosis are not well known. We investigated the conventional vascular risk factors as well as other factors in stroke patients with large artery atherosclerosis. Methods: Using diffusion weighted imaging (DWI) and vascular and cardiologic studies, we selected patients with acute non-cardioembolic cerebral infarcts within the middle cerebral artery (MCA) territory. Patients were divided into two groups: those with atherosclerotic lesions on the carotid sinus (n = 112) and those with isolated lesions on the proximal MCA (n = 160). Clinical features, risk factors, and DWI patterns were compared between groups. Results: There were no differences in conventional risk factors, but markers for inflammation were significantly higher in patients with carotid atherosclerosis than in those with isolated MCA atherosclerosis (p

Background: Detection of multiple acute brain infarcts (MABI) by diffusion weighted magnetic resonance imaging (DWI) may provide information about stroke mechanism in (1) acute lacunar stroke, where evidence of MABI suggests a cause other than small artery disease (SAD), such as embolism or vasculitis (type 1 MABI); or (2) acute non-lacunar stroke, where MABI in the territory of at least two of the aortic branches supplying the brain indicates the presence of aortic or cardiac embolism rather than artery to artery embolism (type 2 MABI). Objective: To evaluate the prevalence of MABI and their impact on aetiological classification and prevention of stroke in patients with acute ischaemic stroke examined with DWI. Methods: 182 consecutive patients defined by DWI were evaluated. Stroke aetiology was classified according to the TOAST criteria, though "lacunar stroke" included patients with possible aetiologies other than SAD. Results: Type 1 MABI were detected in 21/72 patients (29%) with lacunar stroke, and type 2 MABI in 8/110 (7%) with non-lacunar stroke. A possible stroke mechanism different from SAD was found in nine type 1 MABI cases (43%): cardiac embolism (4); other determined aetiology (3); aortic embolism (2). Cardiac (2) or aortic (1) sources of embolism were detected in eight type 2 MABI cases. MABI patients with cardiac or aortic sources of embolism were treated with warfarin, the remainder with aspirin. Conclusions: Detection of type 1 MABI in patients with lacunar stroke improved diagnostic confidence and the choice of antithrombotic treatment. Further study is needed on stroke prevention in MABI cases caused by SAD alone.

International audience; BACKGROUND: Cerebral infarcts are responsible for functional alterations and microscopic tissue damage at distance from the ischaemic area. Such remote effects have been involved in stroke recovery. Thalamic hypometabolism is related to motor recovery in middle cerebral artery (MCA) infarcts but little is known concerning the tissue changes underlying these metabolic changes. Diffusion tensor imaging (DTI) is highly sensitive to microstructural tissue alterations and can be used to quantify in vivo the longitudinal microscopic tissue changes occurring in the thalamus after MCA infarcts in humans. METHODS: Nine patients underwent DTI after an isolated MCA infarct. Mean diffusivity (MD), fractional anisotropy (FA), and thalamic region volume were measured from the first week to the sixth month after stroke onset in these patients and in 10 age matched controls. RESULTS: MD significantly increased in the ipsilateral thalamus between the first and the sixth month (0.766 x 10(-3) mm(2)/s first month; 0.792 x 10(-3) mm(2)/s third month; 0.806 x 10(-3) mm(2)/s sixth month). No significant modification of FA was detected. In six patients, the ipsilateral/contralateral index of MD was higher than the upper limit of the 95% CI calculated in 10 age matched controls. An early decrease of MD preceded the increase of ipsilateral thalamic diffusion in one patient at the first week and in two other patients at the first month. CONCLUSION: After MCA infarcts, an increase in diffusion is observed with DTI in the ipsilateral thalamus later than 1 month after the stroke onset. This is presumably because of the progressive loss of neurons and/or glial cells. In some patients, this increase is preceded by a transient decrease in diffusion possibly related to an early swelling of these cells or to microglial activation. Further studies in larger series are needed to assess the clinical correlates of these findings.

Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke.We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnI) with (a) all-cause mortality over a six month follow up, and (b) in-hospital death or major non-fatal cardiac event (angina, myocardial infarction, or heart failure).cTnI levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10-0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p0.0001, log rank test for trend). On multivariate analysis, cTnI level was an independent predictor of mortality (low positive cTnI, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnI, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnI also predicted a higher risk of the combined endpoint "in-hospital death or non-fatal cardiac event". Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results.cTnI positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnI positive patients can reduce cardiac morbidity and mortality should be the focus of future research.

Objective: To evaluate clinical, biological, and pretreatment imaging variables for predictors of tissue plasminogen activator (tPA) related intracerebral haemorrhage (ICH) in stroke patients. Methods: 48 consecutive patients with hemispheric stroke were given intravenous tPA within seven hours of symptom onset, after computed tomography (CT) and magnetic resonance imaging (MRI) of the brain. Baseline diffusion weighted (DWI) and perfusion weighted (PWI) imaging volumes, time to peak, mean transit time, regional cerebral blood flow index, and regional cerebral blood volume were evaluated. The distribution of apparent diffusion coefficient (ADC) values was determined within each DWI lesion. Results: The symptomatic ICH rate was 8.3% (four of 48); the rate for any ICH was 43.8% (21 of 48). Univariate analysis showed that age, weight, history of hyperlipidaemia, baseline NIHSS score, glucose level, red blood cell count, and lacunar state on MRI were associated with ICH. However, mean 24 hour systolic blood pressure and a hyperdense artery sign on pretreatment CT were the only independent predictors of ICH. Patients with a hyperdense artery sign had larger pretreatment PWI and DWI lesion volumes and a higher NIHSS score. Analysis of the distribution of ADC values within DWI lesions showed that a greater percentage of pixels had lower ADCs ( −6 mm 2 /s) in patients who experienced ICH than in those who did not. Conclusion: Key clinical and biological variables, pretreatment CT signs, and MRI indices are associated with tPA related intracerebral haemorrhage.

Objectives: Cerebral vasospasm remains the leading cause of death and permanent disability after subarachnoid haemorrhage. This study determined whether the method of aneurysm treatment plays an important role in determining the incidence of cerebral vasospasm and its clinical consequences. Methods: Admission data, cranial computed tomography (CT), treatment details, transcranial Doppler (TCD) results, and clinical outcomes of patients who had surgical or endovascular management of their ruptured aneurysm were recorded and subject to multivariate analysis. Results: Between January 1995 and December 1999, 292 eligible patients (206 female, 86 male) had definitive aneurysm treatment at our unit. 212 patients were clipped, 80 coiled. There was no significant difference in patient age, pre-treatment neurological grade, Fisher grade, or timing of treatment in the two groups. 48.3% patients developed TCD detected cerebral vasospasm and 16.1% patients developed permanent ischaemic neurological deficit. At clinical follow up, 84.2% of patients were well (mGOS 1 and 2) with a cumulative death rate of 6.5% from all causes. The only significant predictor of TCD-detected cerebral vasospasm was patient age (inversely, p = 0.004). Increased patient age, vasospasm, poor pre-treatment WFNS, and higher CT Fisher grades correlated with a poor discharge GOS. However, only poor pre-treatment WFNS grade and patient age correlated with poor GOS at follow up (p Conclusion: The treatment method had no influence on the incidence or duration of TCD detected vasospasm and there was no significant difference in outcome at discharge or follow up between those patients who had surgery or endovascular management of their aneurysms.

Background: Aspiration pneumonia is the most important acute complication of stroke related dysphagia. Tube feeding is usually recommended as an effective and safe way to supply nutrition in dysphagic stroke patients. Objective: To estimate the frequency of pneumonia in acute stroke patients fed by nasogastric tube, to determine risk factors for this complication, and to examine whether the occurrence of pneumonia is related to outcome. Methods: Over an 18 month period a prospective study was done on 100 consecutive patients with acute stroke who were given tube feeding because of dysphagia. Intermediate outcomes were pneumonia and artificial ventilation. Functional outcome was assessed at three months. Logistic regression and multivariate regression analyses were used, respectvely, to identify variables significantly associated with the occurrence of pneumonia and those related to a poor outcome. Results: Pneumonia was diagnosed in 44% of the tube fed patients. Most patients acquired pneumonia on the second or third day after stroke onset. Patients with pneumonia more often required endotracheal intubation and mechanical ventilation than those without pneumonia. Independent predictors for the occurrence of pneumonia were a decreased level of consciousness and severe facial palsy. The NIH stroke scale score on admission was the only independent predictor of a poor outcome. Conclusions: Nasogastric tubes offer only limited protection against aspiration pneumonia in patients with dysphagia from acute stroke. Pneumonia occurs mainly in the first days of the illness and patients with decreased consciousness and a severe facial palsy are especially endangered.

Background: Patients who suffer a cerebrovascular event are at high risk of a recurrence. Secondary prevention is crucial in reducing the burden of cerebrovascular disease. Objective: To estimate the percentage of stroke survivors receiving antiplatelet or anticoagulant drugs and to identify factors associated with such treatment. Design: Cross sectional retrospective cohort study. Methods: Data were analysed from a large collaborative observational study, the Italian "silver network" home care project, which collected data (from 1997 to 2001) on patients admitted to home care programmes (n = 5372). Twenty two home health agencies participated in evaluating the implementation of the minimum dataset for home care (MDS-HC) instrument. For the present study, 648 individuals with a diagnosis of stroke were selected and the initial MDS-HC assessment reported. Results: 70% of stroke survivors did not receive any antiplatelet or anticoagulant drugs (95% confidence interval (CI), 66.5 to 73.5). Among all age categories, aspirin and ticlopidine were the two most commonly prescribed drugs. Living alone (odds ratio (OR), 0.49 (95% CI, 0.24 to 0.89)), dependency in activities of daily living (0.66 (0.40 to 0.99)), cognitive impairment (0.58 (0.38 to 0.86)), and low educational level (0.58 (0.34 to 0.98)) were associated with a reduced likelihood of receiving secondary stroke prevention treatment. Cardiac arrhythmias, coronary artery disease, heart failure, and peripheral vascular disease were associated with the use of antiplatelet or anticoagulant treatment. Conclusions: Negative attitudes among physicians with respect to secondary stroke prevention are prevalent and reinforce the need for increased awareness of existing data on the risks and benefits for elderly individuals. Social problems and functional impairment may be issues concerning physicians when deciding whether or not the risks of treatment exceed the benefit.

Although dysarthria-clumsy hand syndrome (DCHS) is a well known and infrequent lacunar syndrome, there are few data regarding the spectrum of associated clinical characteristics, anatomical site of lesion, and aetiopathogenetic mechanisms. We report a clinical description of this subtype of lacunar stroke based on data collected from a prospective acute stroke registry.From 2500 acute stroke patients included in a hospital based prospective stroke registry over a 12-year period, 35 patients were identified as having DCHS.DCHS accounted for 1.6% of all acute stroke patients (35/2110), 1.9% of acute ischaemic stroke (35/1840), and 6.1% of lacunar syndromes (35/570) admitted consecutively to a neurology department and included in the stroke registry over this period. The results supported the lacunar hypothesis in 94.3% of patients (n = 33). Atherothrombotic and cardioembolic infarction occurred in only one patient each (2.9%). No patient with DCHS had an intracerebral haemorrhage. Outcome was good (mortality in hospital 0%, symptom free at discharge 45.7%). After multivariate analysis, absence of limitation at discharge, limb weakness but not cerebellar-type ataxia, and internal capsule (40%), pons (17%), and corona radiata (8.6%) location were significantly associated with DCHS.DCHS is a rare cerebrovascular syndrome, and supports the criteria of the lacunar hypothesis. The majority of patients in this study had internal capsule infarcts. The prognosis is good with striking similarity compared with other types of lacunar strokes. There are important differences between DCHS and non-lacunar strokes. Internal capsule and pons are the most frequent cerebral sites.

Objective: To determine long term functional outcome and length of survival of patients undergoing decompressive craniectomy for space occupying infarction of the middle cerebral artery (MCA), and to identify risk factors associated with death and unfavourable outcomes

Objectives: To evaluate the results of treatment of patients with a ruptured intracranial aneurysm treated by a single experienced vascular neurosurgeon in the period prior to the introduction of endovascular coiling. Methods: Over a mean (SD) period of 9 (2) years, between January 1990 and June 1999, 245 consecutive patients with ruptured intracranial aneurysms were treated. Patients’ details were obtained from a database that had been constructed prospectively. The patients consisted of all those patients treated by the senior author (Mr Maurice-Williams) over this period—that is, every third day on call at his unit. During this period, all patients under the age of 75 years with a diagnosis of subarachnoid haemorrhage were admitted to the neurosurgical unit as soon as was practicable regardless of clinical grade. Results: Of 245 patients, 190 (77.6%) underwent treatment by open surgery using standard microsurgical techniques. At 1 year, the mortality of the operated patients was 2.6%, while 89.5% of the patients had a Glasgow Outcome Score (GOS) of 4 and 5. The overall management outcome (all patients treated, including operated and non-operated cases) at 1 year was: 17.1 % dead while 74.3% had GOS 4 and 5. Of the 190 patients who underwent surgery, 38 (20%) required additional operations, totalling 72 operations in all. Of these, 32 were for hydrocephalus and 17 for the evacuation of intracranial haematomas/collections. Complications of surgery occurred in 56 patients (29.5%). Conclusion: Open surgery, despite good eventual results, is associated with a significant rate of re-operations and complications that would probably be largely avoided with endovascular treatment. Nevertheless, although endovascular coiling has these immediate advantages over surgery it is still not certain that the long term results will be superior to surgery which leads to permanent obliteration of the aneurysm. There may still be a need for open surgery in the future.

Objective: To evaluate the results of surgical treatment options for chronic subdural haematoma in contemporary neurosurgery according to evidence based criteria. Methods: A review based on a Medline search from 1981 to October 2001 using the phrases “subdural haematoma” and “subdural haematoma AND chronic”. Articles selected for evaluation had at least 10 patients and less than 10% of patients were lost to follow up. The articles were classified by three classes of evidence according to criteria of the American Academy of Neurology. Strength of recommendation for different treatment options was derived from the resulting degrees of certainty. Results: 48 publications were reviewed. There was no article that provided class I evidence. Six articles met criteria for class II evidence and the remainder provided class III evidence. Evaluation of the results showed that twist drill and burr hole craniostomy are safer than craniotomy; burr hole craniostomy and craniotomy are the most effective procedures; and burr hole craniostomy has the best cure to complication ratio (type C recommendation). Irrigation lowers the risk of recurrence in twist drill craniostomy and does not increase the risk of infection (type C recommendation). Drainage reduces the risk of recurrence in burr hole craniostomy, and a frontal position of the drain reduces the risk of recurrence (type B recommendation). Drainage reduces the risk of recurrence in twist drill craniostomy, and the use of a drain does not increase the risk of infection (type C recommendation). Burr hole craniostomy appears to be more effective in treating recurrent haematomas than twist drill craniostomy, and craniotomy should be considered the treatment of last choice for recurrences (type C recommendation). Conclusions: The three principal techniques—twist drill craniostomy, burr hole craniostomy, and craniotomy—used in contemporary neurosurgery for chronic subdural haematoma have different profiles for morbidity, mortality, recurrence rate, and cure rate. Twist drill and burr hole craniostomy can be considered first tier treatment, while craniotomy may be used as second tier treatment. A cumulative summary of data shows that, overall, the postoperative outcome of chronic subdural haematoma has not improved substantially over the past 20 years.

Background: Despite its importance for acute stroke management, little is known about the underlying pathophysiology when patients with acute stroke are classified using clinical methods. Objective: To examine the relation between the magnetic resonance defined stroke subtype and clinical stroke classifications using diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), and angiographic magnetic resonance techniques. Methods: Consecutive patients with clinical syndromes consistent with acute anterior circulation stroke were assessed clinically within six hours of onset and scanned as soon as possible using multimodal magnetic resonance imaging (MRI). Patients were classified clinically into total or partial anterior circulation syndromes using the Oxford classification, or according the severity of the National Institutes of Health stroke scale (NIHSS) (severe > 15; mild/moderate ≤ 15). At day seven, patients were classified by combining clinical course and MRI data as misdiagnosed, misclassified, suffering transient ischaemic attack, infarct with recanalisation, or infarction with persisting occlusion. Patients with occlusion were further divided on the basis of a large diffusion–perfusion mismatch. Results: 84 patients with clinical anterior circulation syndromes were studied. Using the NIHSS, 42 were mild to moderate (0–15) and 42 were severe (> 15). There were 42 with partial anterior circulation syndromes (PACS) and 42 with total anterior circulation syndromes (TACS). Patients with TACS or severe stroke were more likely to have actually suffered a stroke (Fischer's exact test, p = 0.01), to have a correctly classified stroke (χ2 28.2, p < 0.01), to have persisting occlusion (χ2 30.6, p < 0.01), and to have a large DWI–PWI mismatch (χ2 17.1, p < 0.01). Conclusions: There is more inaccuracy in patients presenting with acute PACS or clinically mild to moderate anterior circulation stroke than in those with TACS or severe acute stroke syndromes. The latter appear more likely to be the targets for acute stroke interventions, as they include a significantly higher proportion of patients with persisting occlusion and diffusion/perfusion mismatch.

OBJECTIVES: Diffusion weighted brain imaging (DWI) is used in acute stroke, and also shows an acute ischaemic lesion in most transient ischamic attack (TIA) patients scanned acutely. However, it may also be useful in identifying subacute ischaemic lesions in patients with minor stroke or TIA who present several weeks after symptom onset. This study investigated the sensitivity and the observer reproducibility of DWI in cerebral TIA and minor ischaemic stroke patients scanned more than two weeks after the last symptomatic event. METHODS: Consecutive patients underwent magnetic resonance imaging (T2, DWI, ADC). The presence of clinically appropriate lesions was assessed by two independent observers, and related to the type of presenting event, the NIH score, persistence of symptoms and signs, and the time since the presenting event. RESULTS: 101 patients (53 men) were scanned at a median time of 21 days (IQR=17-28) after symptom onset. Reproducibility of the assessment of DWI abnormalities was high: interobserver agreement =97% (kappa=0.94, p4 weeks after symptom onset. In minor stroke patients, the presence of a clinically appropriate lesion was associated with persistent symptoms (63% versus 36%; p=0.12) and signs (64% versus 33%, p=0.06) at the time of scanning. CONCLUSIONS: DWI shows a clinically appropriate ischaemic lesion in more than half of minor stroke patients presenting more than two weeks after the symptomatic event, but only in a small proportion of patients with TIA. The persistence of lesions on DWI is closely related to markers of severity of the ischaemic event. These results justify larger studies of the clinical usefulness of DWI in subacute minor stroke.

The appropriate management of unruptured intracranial aneurysms depends on a complete understanding of their natural history and on the risks and efficacy of treatment options. There is little current data on the risks of endovascular therapy for these aneurysms. The aim of this study was to assess outcome of endovascular treatment of unruptured intracranial aneurysms.A retrospective analysis was performed on all unruptured aneurysms treated by Guglielmi detachable (GD) coils at this institution from 1994 to 2000.Seventy three unruptured aneurysms were treated in 62 patients. There were 52 female and 10 male patients, with a median age of 55.7 years. Clinical background was: subarachnoid haemorrhage due to rupture of an additional aneurysm (40), headache (4), third nerve palsy (four), familial (four), and incidental (10). There were 14 technical failures with no clinical sequelae. Four procedural complications occurred (5.5%, 95% confidence interval (95% CI) 0.3% to 10.9%). One patient had temporary clinical sequelae (1.4%, 95% CI 0% to 2.7%); 79% of treated aneurysms had stable occlusions at follow up, 10.5% showed improved occlusion grade, 10.5% showed some recurrence, and three patients have required retreatment. Follow up modified Glasgow outcome scores were grade 1, 71%; grade 2, 18%; grade 3, 3%; grade 4, 3%. There were no deaths or haemorrhages during the follow up period. Two patients died as a result of complications from subarachnoid haemorrhage.The endovascular treatment of patients with unruptured aneurysms is safe with few clinical or procedural complications. Poor outcomes were only seen in those patients who presented with subarachnoid haemorrhage due to rupture of an aneurysm at another site.