No space Left for Intravenous thrombolysis in acute stroke

Recent successful clinical trials of endovascular thrombectomy for large artery ischaemic stroke have established the value of this treatment modality as an adjunct to intravenous thrombolysis, not as an alternative: thrombectomy delivery was undertaken in the context of highly efficient networks for acute thrombolysis delivery and the great majority of patients received IV thrombolytic drug treatment. Even for the minority of acute stroke patients for whom thrombectomy is potentially relevant, access will be limited by geography and service infrastructure. Developments in intravenous thrombolysis in the near future will likely produce safer and more effective intravenous treatments. Intravenous thrombolysis will remain the first line of treatment for the great majority of acute stroke patients

Neuroimaging as a selection tool and endpoint in preclinical and clinical trials

Standard imaging in acute stroke enables the exclusion of non-stroke structural CNS lesions and cerebral haemorrhage from clinical and pre-clinical ischaemic stroke trials. In this review, the potential benefit of imaging (e.g., angiography and penumbral imaging) as a translational tool for trial recruitment and the use of imaging endpoints are discussed for both clinical and pre-clinical stroke research. The addition of advanced imaging to identify a “responder” population leads to reduced sample size for any given effect size in phase 2 trials and is a potentially cost-efficient means of testing interventions. In pre-clinical studies, technical failures (failed or incomplete vessel occlusion, cerebral haemorrhage) can be excluded early and continuous multimodal imaging of the animal from stroke onset is feasible. Pre- and post-intervention repeat scans provide real time assessment of the intervention over the first 4–6 h. Negative aspects of advanced imaging in animal studies include increased time under general anaesthesia, and, as in clinical studies, a delay in starting the intervention. In clinical phase 3 trial designs, the negative aspects of advanced imaging in patient selection include higher exclusion rates, slower recruitment, overestimated effect size and longer acquisition times. Imaging may identify biological effects with smaller sample size and at earlier time points, compared to standard clinical assessments, and can be adjusted for baseline parameters. Mechanistic insights can be obtained. Pre-clinically, multimodal imaging can non-invasively generate data on a range of parameters, allowing the animal to be recovered for subsequent behavioural testing and/or the brain taken for further molecular or histological analysis

Response by Bivard et al to letter regarding article, "Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials"

No abstract available

Cracking the role of cocaine in stroke

No abstract available

Thrombolysis and thrombectomy for acute ischaemic stroke

The likelihood of disability-free recovery after acute ischemic stroke is significantly improved by reperfusion either by intravenous thrombolytic drug treatment or with endovascular mechanical thrombectomy in selected cases. The use of intravenous thrombolysis is limited by the short treatment window and you need to assess individual balance of benefit and risk of symptomatic intracranial haemorrhage. Benefit is greater for shorter onset-to-reperfusion time intervals, requiring optimisation of pre-hospital and in-hospital pathways. Symptomatic haemorrhage is more likely with more severe strokes, but a greater proportion of patients are left free of disability than suffer a treatment-related haemorrhage at all levels of severity. Extracranial haemorrhage and orolingual angioedema are less common complications. Endovascular mechanical thrombectomy can be used in selected patients with imaging-proven large artery occlusion. Successful therapy depends on well-organised services that can deliver treatment within a short time window at centres with adequate expertise to perform the procedure

Iodinated contrast media and cerebral hemorrhage after intravenous thrombolysis

<p>Background and Purpose: Iodinated contrast is increasingly used in CT perfusion or angiographic examinations in acute stroke. Increased risk of intracranial hemorrhage (ICH) complicating microcatheter contrast injections has recently been reported in the second Interventional Management of Stroke (IMS 2) trial with contrast toxicity potentially contributory.</p> <p>Methods: We reviewed clinical and radiological data on all patients treated with intravenous alteplase at a single center between May 2003 and November 2008.</p> <p>Results: Of 312 patients treated with intravenous alteplase, 69 (22.1%) received intravenous iodinated contrast in volumes between 50 and 150 mL. Incidence of symptomatic ICH defined as per European Cooperative Acute Stroke Study 2 was 16 of 312 (5.1%; 95% CI, 2.7% to 7.6%); among patients not given contrast, it was 12 of 243 (4.9%; 2.2% to 7.7%) compared with 4 of 69 (5.8%; 0.3% to 11.3%) in those given contrast. Incidence of symptomatic ICH defined as per Safe Implementation of Thrombolysis in Stroke-MOnitoring Study (SITS-MOST) criteria was 12 of 312 (3.9%; 1.7% to 6%), 9 of 243 (3.7%; 1.3% to 6%) among those not given contrast, and 3 of 69 (4.4%; 95% CI, -0.5% to 9.2%) among those given contrast. Patients with symptomatic ICH were older, had higher pretreatment National Institutes of Health Stroke Scale, and blood glucose than those without symptomatic ICH. In logistic regression analysis, pretreatment blood glucose was the only significant predictor of symptomatic ICH by either definition (OR, 1.23; 95% CI, 1.03 to 1.48 per mmol/L increment; P=0.024). Contrast administration or dose was not associated with symptomatic ICH.</p> <p>Conclusions: Intravenous iodinated contrast in doses typically required for CT angiography and perfusion imaging was not associated with symptomatic intracranial hemorrhage in patients treated with alteplase.</p&gt

Hyperglycaemia does not increase perfusion deficits after focal cerebral ischaemia in male Wistar rats

Background: Hyperglycaemia is associated with a worse outcome in acute ischaemic stroke patients; yet the pathophysiological mechanisms of hyperglycaemia-induced damage are poorly understood. We hypothesised that hyperglycaemia at the time of stroke onset exacerbates ischaemic brain damage by increasing the severity of the blood flow deficit. Methods: Adult, male Wistar rats were randomly assigned to receive vehicle or glucose solutions prior to permanent middle cerebral artery occlusion. Cerebral blood flow was assessed semi-quantitatively either 1 h after middle cerebral artery occlusion using 99mTc-D, L-hexamethylpropyleneamine oxime (99mTc-HMPAO) autoradiography or, in a separate study, using quantitative pseudo-continuous arterial spin labelling for 4 h after middle cerebral artery occlusion. Diffusion weighted imaging was performed alongside pseudo-continuous arterial spin labelling and acute lesion volumes calculated from apparent diffusion coefficient maps. Infarct volume was measured at 24 h using rapid acquisition with refocused echoes T2-weighted magnetic resonance imaging. Results: Glucose administration had no effect on the severity of ischaemia when assessed by either 99mTc-HMPAO autoradiography or pseudo-continuous arterial spin labelling perfusion imaging. In comparison to the vehicle group, apparent diffusion coefficient–derived lesion volume 2–4 h post-middle cerebral artery occlusion and infarct volume 24 h post-middle cerebral artery occlusion were significantly greater in the glucose group. Conclusions: Hyperglycaemia increased acute lesion and infarct volumes but there was no evidence that the acute blood flow deficit was exacerbated. The data reinforce the conclusion that the detrimental effects of hyperglycaemia are rapid, and that treatment of post-stroke hyperglycaemia in the acute period is essential but the mechanisms of hyperglycaemia-induced harm remain unclear

Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak −48, −18, −14; ZE = 5.65, pFWEcorr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = −0.77, p < 0.001) and better executive performance (r = 0.56, p = 0.011). This preliminary study provides evidence for associations between cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population

Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. validation using [14C]2-deoxyglucose autoradiography

Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T2* MRI (T2* OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T2* signal change during OC. [14C]2-deoxyglucose (2-DG) autoradiography was combined with T2* OC to determine metabolic status of T2*-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147±32 minutes after stroke, T2* signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T2*-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T2* signal increase of 9.22%±3.9% (mean±s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T2* signal change was negligible in ischemic core, 3.2%±0.78% in contralateral regions, and 1.41%±0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue follow

Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra

We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2* signal change during ‘oxygen challenge’ (OC, 5 mins 100% O2). During OC, T2* increase reflects O2 binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2* acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2* signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2* and apparent diffusion coefficient (ADC) map coregistration revealed that the T2* signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2* and ADC maps coregistered with histology revealed a T2* signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra