Induced hypertension for the treatment of acute MCA occlusion beyond the thrombolysis window: case report

BACKGROUND: A minority of stroke patients is eligible for thrombolytic therapy. Small pilot case series have hinted that elevation of incident arterial blood pressure might be associated with a favorable prognosis either in acute or subacute stroke. However, these patients were not considered for thrombolytic therapy and were not followed – up systematically. We used pharmacologically induced hypertension in a stroke patient with middle cerebral artery (MCA) occlusion ineligible for thrombolysis that was followed-up by radiological, clinical and functional outcome assessment. CASE PRESENTATION: A patient with acute embolic MCA occlusion producing a large, ischemic penumbra confirmed by perfusion CT was treated by induced hypertension with phenylephrine started within 4 h of admission. Increase in the mean arterial pressure by 20% led to a reduction of neurological deficit by 3 points on the National Institute of Stroke Scale. MRI and CT scans performed during phenylephrine infusion showed the presence of limited subcortical and cortical infarct changes that were clearly less extensive than the perfusion deficit in the brain perfusion CT at baseline, found in the absence of MCA patency. No complications due to induced hypertension therapy occurred. Moderate functional improvement up to modified Rankin scale 2 at follow up took place. CONCLUSION: Induced hypertension in acute ischemic stroke seems clinically feasible and may be beneficial in selected normo- or hypotensive stroke patients not eligible for thrombolytic recanalization therapy

Haptoglobin Hp1 Variant Does Not Associate with Small Vessel Disease

Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases-a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort

An emergency clinical pathway for stroke patients – results of a cluster randomised trial (isrctn41456865)

BACKGROUND: Emergency Clinical Pathways (ECP) for stroke have never been tested in randomized controlled trials (RCTs). OBJECTIVE: To evaluate the effectiveness of an ECP for stroke patients in Latium (Italy) emergency system. METHODS: cluster-RCT designed to compare stroke patient referrals by Emergency Medical Service (EMS) and Emergency Room (ER) health professionals trained in the ECP, with those of non-trained EMS and ER controls. Primary outcome measure was the proportion of eligible (aged /= 80 and symptom onset /= 6 hours) stroke patients referred to a stroke unit (SU). Intention to treat (ITT) and per-protocol (PP) analyses were performed, and risk ratios (RR) adjusted by age, gender and area, were calculated. RESULTS: 2656 patients in the intervention arm and 2239 in the control arm required assistance; 78.3% of the former and 80.6% of the latter were admitted to hospitals, and respectively 74.8% and 78.3% were confirmed strokes. Of the eligible confirmed strokes, 106/434 (24.4%) in the intervention arm and 43/328 (13.1%) in the control arm were referred to the SU in the ITT analysis (RR = 2.01; 95% CI: 0.79-4.00), and respectively 105/243 (43.2%) and 43/311 (13.8%) in the PP analysis (RR = 3.21; 95%CI: 1.62-4.98). Of patients suitable for i.v. thrombolysis, 15/175 (8.6%) in the intervention arm and 2/115 (1.7%) in the control arm received thrombolysis (p = 0.02) in the ITT analysis, and respectively 15/99 (15.1%) and 2/107 (1.9%)(p = 0.001) in the PP analysis. CONCLUSION: Our data suggest potenti efficiency and feasibility of an ECP. The integration of EMS and ERs with SU networks for organised acute stroke care is feasible and may ameliorate the quality of care for stroke patients. TRIAL REGISTRATION: Current Controlled Trials (ISRCTN41456865)

Circulating CD133+CD34+ progenitor cells inversely correlate with soluble ICAM-1 in early ischemic stroke patients

<p>Abstract</p> <p>Background and Purpose</p> <p>Both endothelial progenitor cells (EPC) and markers of neuroinflammation are candidate biomarkers for stroke severity and outcome prediction. A relationship between EPC and neuroinflammatory markers in early stroke is not fully elucidated. The objectives were to investigate correlations between EPC and neuroinflammation markers (adhesion molecules ICAM-1, VCAM-1, E-selectin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, endothelin (ET)-1, markers of tissue injury (matrix metalloproteinases (MMP)-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1) in early stroke patients.</p> <p>Methods</p> <p>We prospectively recruited symptomatic patients with ischemic cerebrovascular disease. We assessed stroke severity by using of acute (diffusion-weighted imaging (DWI) and final lesion volumes (fluid attenuated inversion recovery (FLAIR). We measured serum soluble ICAM-1, VCAM-1, E-selectin, MMP-9, TIMP-1 and plasma TNF-α, IL-6, ET-1 by ELISA, and quantified EPC in mononuclear fraction of peripheral blood on days 1 and 3 in 17 patients (mean(SD) age 62(14), with admission National Institutes of Health Stroke Scale (NIHSS) 10(8)) selected from 175 patients with imaging confirmed ischemic stroke. Non-parametric statistics, univariate and multivariate analysis were used.</p> <p>Results</p> <p>Only ICAM-1 inversely correlated with EPC subset CD133+CD34+ on day 1 (Spearman r = -0.6, p < 0.01) and on day 3 (r = -0.967, p < 0.001). This correlation remained significant after adjustment for age and NIHSS (beta -0.992, p < 0.004), for glucose and systolic blood pressure (beta -0.86, p < 0.005), and for white blood cells and hematocrit (beta -1.057, p < 0.0001) on day 3. MMP-9 (r = 0.509, p < 0.04) and MMP-9/TIMP-1 (r = 0.59, p < 0.013) on day 1 correlated with acute lesion volume. Both IL-6 (r = 0.624, p < 0.01) and MMP-9/TIMP-1 (r = 0.56, p < 0.02) correlated with admission NIHSS.</p> <p>Conclusion</p> <p>Our study showed that high ICAM-1 is associated with low CD133+CD34+subset of EPC. Biomarkers of neuroinflammation may predict tissue injury and stroke severity in early ischemia.</p

Serum cytokine and glucose levels as predictors of poststroke fatigue in acute ischemic stroke patients

Fatigue is a common but often overlooked symptom after stroke. This study investigated whether stroke type, infarct volume, and laterality, as well as the levels of various cytokines and other blood components in the acute phase of acute ischemic stroke (AIS), can predict the level of fatigue at 6, 12, and 18 months after its onset. In 45 patients with acute stroke, serum levels of C-reactive protein, hemoglobin, glucose, and 13 cytokines were measured within 72 h of stroke onset. The cytokine measurements were performed using BioPlex XMap technology (Luminex). The acute serum levels of interleukin (IL)-1β and glucose were positively correlated with the score on the Fatigue Severity Scale (FSS) at 6 months after the stroke (r = 0.37, p = 0.015, and r = 0.37, p = 0.017, respectively). The acute serum levels of IL-ra and IL-9 were negatively correlated with FSS score at 12 months after the stroke (r = −0.38, p = 0.013, and r = −0.36, p = 0.019, respectively). The FSS score at 12 months after stroke was significantly lower in patients with radiologically confirmed infarction than in those without such confirmation (p = 0.048). The FSS score at 18 months was not correlated with any of the measured variables. High acute serum levels of glucose and IL-1β, and low IL1-ra and IL-9 may predict fatigue after AIS, indicating that the development of poststroke fatigue can be accounted for by the proinflammatory response associated with AIS. These novel findings support a new cytokine theory of fatigue after stroke. However, more research is needed to validate the results of this study

Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Interruption of flow through of cerebral blood vessels results in acute ischemic stroke. Subsequent breakdown of the blood brain barrier increases cerebral injury by the development of vasogenic edema and secondary hemorrhage known as hemorrhagic transformation (HT). Diabetes is a risk factor for stroke as well as poor outcome of stroke. The current study tested the hypothesis that diabetes-induced changes in the cerebral vasculature increase the risk of HT and augment ischemic injury.</p> <p>Methods</p> <p>Diabetic Goto-Kakizaki (GK) or control rats underwent 3 hours of middle cerebral artery occlusion and 21 h reperfusion followed by evaluation of infarct size, hemorrhage and neurological outcome.</p> <p>Results</p> <p>Infarct size was significantly smaller in GK rats (10 ± 2 vs 30 ± 4%, p < 0.001). There was significantly more frequent hematoma formation in the ischemic hemisphere in GK rats as opposed to controls. Cerebrovascular tortuosity index was increased in the GK model (1.13 ± 0.01 vs 1.34 ± 0.06, P < 0.001) indicative of changes in vessel architecture.</p> <p>Conclusion</p> <p>These findings provide evidence that there is cerebrovascular remodeling in diabetes. While diabetes-induced remodeling appears to prevent infarct expansion, these changes in blood vessels increase the risk for HT possibly exacerbating neurovascular damage due to cerebral ischemia/reperfusion in diabetes.</p

Inflammatory mechanisms in ischemic stroke: therapeutic approaches

Acute ischemic stroke is the third leading cause of death in industrialized countries and the most frequent cause of permanent disability in adults worldwide. Despite advances in the understanding of the pathophysiology of cerebral ischemia, therapeutic options remain limited. Only recombinant tissue-plasminogen activator (rt-PA) for thrombolysis is currently approved for use in the treatment of this devastating disease. However, its use is limited by its short therapeutic window (three hours), complications derived essentially from the risk of hemorrhage, and the potential damage from reperfusion/ischemic injury. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. This review will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke and potential therapeutic strategies that target neuroinflammation and the innate immune system. Currently, little is known about endogenous counterregulatory immune mechanisms. However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies

The thrombotic potential of oral pathogens

In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets