Interleukin-1 is a pro-inflammatory cytokine that has numerous biological effects, including activation of many inflammatory processes (through activation of T cells, for example), induction of expression of acute-phase proteins, an important function in neuroimmune responses and direct effects on the brain itself. There is now extensive evidence to support the direct involvement of interleukin-1 in the neuronal injury that occurs in both acute and chronic neurodegenerative disorders. This article discusses the key evidence of a role for interleukin-1 in acute neurodegeneration - for example, stroke and brain trauma - and provides a rationale for targeting the interleukin-1 system as a therapeutic strategy.

Background: Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome.

Objectives: The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents. The endogenous, highly selective, IL-1 receptor antagonist (IL-1ra) protects against ischaemic cerebral injury in a range of experimental settings, and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia. We report here the first randomised, double blind, placebo controlled trial of recombinant human IL-1ra (rhIL-1ra) in patients with acute stroke. Methods: Patients within 6 hours of the onset of symptoms of acute stroke were randomised to rhIL-1ra or matching placebo. Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds, followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months, serial blood samples were collected for biological markers up to 3 months, and 5-7 day brain infarct volume was measured by computed tomography. Results: No adverse events were attributed to study treatment among 34 patients randomised. Markers of biological activity, including neutrophil and total white cell counts, C reactive protein, and IL-6 concentrations, were lower in rhIL-1ra treated patients. Among patients with cortical infarcts, clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated. Conclusions: These data suggest that rhIL-1ra is safe and well tolerated in acute stroke. In addition, rhIL1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke. Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke.

C ardioembolism accounts for 17% to 30% of all ischemic strokes.1,2 Some data suggest that >50% of these are because of atrial fibrillation (AF).3 Paroxysmal AF (PAF) is often undetected because characteristics such as short duration, episodic, and frequently asymptomatic nature make it challenging to diagnose at the bedside, leading to suboptimal secondary prevention. 4 It is likely that a proportion of strokes labeled as cryptogenic are cardioembolic in origin because of occult AF. 5,6 Furthermore, ≥2 factors contributing to stroke risk may coexist: even patients with an identified risk factor for nonembolic stroke may have occult cardioembolism.Detection rate of new AF from a standard 12-lead ECG after ischemic stroke/transient ischemic attack (TIA) is ≈2% to 5% 7,8 and from 24-hour Holter is 2% to 6%. [9][10][11] The European Stroke Organization 12 and the American Heart Association (AHA)/ American Stroke Association 13 recommend that 24-hour Holter monitoring is used to detect occult AF/PAF when suspected, and no other cause for stroke is found. However, the optimum timing, duration, setting (outpatient or inpatient), and method of monitoring to maximize the detection of PAF after stroke/ TIA are unclear. Furthermore, diagnostic criteria used for PAF during monitoring may vary and have implications for risk of recurrence. We therefore undertook a systematic review and meta-analysis with the following objectives:To determine the overall rate of detection of any new AF with cardiac monitoring (invasive and noninvasive) after ischemic stroke/TIA. To evaluate detection rates of AF in selected versus unselected patients with stroke/TIA. To explore the influence of duration of monitoring on detection rates of AF.Background and Purpose-Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack. Methods-Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring. Results-A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%-14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%-18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%-8.3%). There was substantial heterogeneity ev...

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Impact of centralising acute stroke services in English metropolitan areas on mortality and length of hospital stay: difference-in-differences analysis OPEN ACCESS Stephen AbstractObjective To investigate whether centralisation of acute stroke services in two metropolitan areas of England was associated with changes in mortality and length of hospital stay.Design Analysis of difference-in-differences between regions with patient level data from the hospital episode statistics database linked to mortality data supplied by the Office for National Statistics.Setting Acute stroke services in Greater Manchester and London, England.Participants 258 915 patients with stroke living in urban areas and admitted to hospital in January 2008 to March 2012.Interventions "Hub and spoke" model for acute stroke care. In London hyperacute care was provided to all patients with stroke. In Greater Manchester hyperacute care was provided to patients presenting within four hours of developing symptoms of stroke. Main outcome measuresMortality from any cause and at any place at 3, 30, and 90 days after hospital admission; length of hospital stay. ResultsIn London there was a significant decline in risk adjusted mortality at 3, 30, and 90 days after admission. At 90 days the absolute reduction was −1.1% (95% confidence interval −2.1 to −0.1; relative reduction 5%), indicating 168 fewer deaths (95% confidence interval 19 to 316) during the 21 month period after reconfiguration in London. In both areas there was a significant decline in risk adjusted length of hospital stay: −2.0 days in Greater Manchester (95% confidence interval −2.8 to −1.2; 9%) and −1.4 days in London (−2.3 to −0.5; 7%). Reductions in mortality and length of hospital stay were largely seen among patients with ischaemic stroke.Conclusions A centralised model of acute stroke care, in which hyperacute care is provided to all patients with stroke across an entire metropolitan area, can reduce mortality and length of hospital stay. IntroductionStroke is a leading cause of mortality and disability worldwide. Each year in England an estimated 125 000 people have a stroke and 40 000 of them die.2 Organised inpatient stroke unit care, which is provided by multidisciplinary teams that exclusivelyCorrespondence to: S Morris steve.morris@ucl.ac.uk Extra material supplied by the author (see

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