Fidelity to and utility of a home blood pressure self-monitoring regime in people with pre-hypertension: results from the REVERSE study.

INTRODUCTION: Around 40% of adults have pre-hypertension (120-139/80-89mmHg) increasing their risk of developing hypertension and associated cardiovascular conditions. Guidance on pre-hypertension management focuses on improving lifestyle. Self-monitoring may improve awareness and understanding of blood pressure (BP) for people with pre-hypertension, allowing them to modify their lifestyle risks. AIM: To determine the fidelity to and utility of a home BP self-monitoring regime in people with pre-hypertension. METHOD: This sub-study is part of a larger prospective, non-randomised feasibility study. Individuals with pre-hypertension were identified via GP records and pharmacy NHS Health Checks in Northwest England. Participants received training for home BP self-monitoring. They were asked to complete two readings (leaving a 5-minute interval) on the first three days of the month for six months, colour-code their readings and take action using a simple algorithm, then send them to the research team within 7 days. RESULTS: Eighty participants (aged 40-79, mean=59) enrolled. The majority were female (n=45, 56%), White British (n=79, 99%), and had not previously monitored their BP (n=55, 69%). Seventy-five (94%) participants completed the training. Sixty-one (81%) received online training and 14 (19%) opted for a face-to-face session. Sixty-one (81%) completed all six months of readings, 51 (68%) also returned them on time. All in-person training participants completed all six months of readings on time. Reasons for non-compliance to the protocol included battery issues, forgetting, and struggling to find a consistent time for readings. CONCLUSION: Home BP self-monitoring can be feasible and easily implementable for people with pre-hypertension - however, some barriers were identified.

Non-pharmacological interventions for the reduction and maintenance of blood pressure in people with prehypertension: a systematic review protocol.

INTRODUCTION: Prehypertension is defined as blood pressure that is above the normal range but not high enough to be classed as hypertension. Prehypertension is a warning of development of hypertension as well as a risk for cardiovascular disease, heart attack and stroke. In the UK, non-pharmacological interventions are recommended for prehypertension management but no reviews have focused on the effectiveness of these types of interventions solely in people with prehypertension. Therefore, the proposed systematic review will assess the clinical effectiveness and cost-effectiveness of non-pharmacological interventions in reducing or maintaining blood pressure in prehypertensive people. METHODS AND ANALYSIS: This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases/trial registries that will be searched to identify relevant randomised controlled trials (RCTs) and economic evaluations include Medline, EMBASE, CINAHL, PsycINFO, CENTRAL, the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, Cochrane Library, Scopus and the International HTA Database. Search terms have been identified by the team including an information specialist. Three reviewers will be involved in the study selection process. Risk of bias will be evaluated using the Cochrane risk-of-bias tool for RCTs and the Consensus Health Economic Criteria list for economic evaluations. Findings from the included studies will be tabulated and synthesised narratively. Heterogeneity will be assessed through visual inspection of forest plots and the calculation of the χ2 and I2 statistics and causes of heterogeneity will be assessed where sufficient data are available. If possible, we plan to investigate differential effects on specific subgroups and from different types of interventions using meta-regression. Where relevant, the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) will be used to assess the certainty of the evidence found. ETHICS AND DISSEMINATION: Ethical approval is not needed. Results will be published in a peer-reviewed journal, disseminated via the wider study website and shared with the study sites and participants. REGISTRATION DETAILS: The review is registered with PROSPERO (CRD420232433047).

Risk reduction intervention for raised blood pressure (REVERSE): protocol for a mixed-methods feasibility study.

INTRODUCTION: Around 40% of adults have pre-hypertension (blood pressure between 120-139/80-89), meaning they are at increased risk of developing hypertension and other cardiovascular disease-related conditions. There are limited studies on the management of pre-hypertension; however, guidance recommends that it should be focused on lifestyle modification rather than on medication. Self-monitoring of blood pressure could allow people to monitor and manage their risk status and may allow individuals to modify lifestyle factors. The purpose of this study is to determine the feasibility and acceptability, to both healthcare professionals and people with pre-hypertension, of blood pressure self-monitoring. METHODS AND ANALYSIS: A prospective, non-randomised feasibility study, with a mixed-methods approach will be employed. Eligible participants (n=114) will be recruited from general practices, pharmacies and community providers across Lancashire and South Cumbria. Participants will self-monitor their blood pressure at home for 6 months and will complete questionnaires at three timepoints (baseline, 6 and 12 months). Healthcare professionals and participants involved in the study will be invited to take part in follow-up interviews and a focus group. The primary outcomes include the willingness to engage with the concept of pre-hypertension, the acceptability of self-monitoring, and the study processes. Secondary outcomes will inform the design of a potential future trial. A cost-analysis and cost-benefit analysis will be conducted. ETHICS AND DISSEMINATION: Ethics approval has been obtained from London-Fulham NHS Research Ethics Committee, the University of Central Lancashire Health Ethics Review Panel and the HRA. The results of the study will be disseminated via peer-reviewed publications, feedback to service users and healthcare professionals, and to professional bodies in primary care and pharmacy. TRIAL REGISTRATION NUMBER: ISRCTN13649483.

Beach litter sources around Nuuk, Greenland: An analysis by UArctic summer school graduate course students.

Modeling studies illustrate the potential for long-range transport of plastics into the Arctic, although the degree to which this occurs remains relatively undocumented. We utilised a teaching exercise at a UArctic summer school graduate course in Nuuk, Greenland to conduct a preliminary in-depth analysis of beach litter sources in the Nuup Kangerlua fjord. Students and instructors collected and analysed 1800 litter items weighing 200 kg from one location in the fjord and another at its mouth. The results suggest a predominance of local sources to macrolitter, rather than long-range transport from Europe. Fisheries-related items and rope were common. Packaging which could be identified was largely suspected to be products distributed in Greenland, and soft plastics, which rarely disperse far from its source, were also common. The results suggest local measures to reduce mismanaged waste and emissions from fisheries are important for reducing marine litter in West Greenland.

Online advice for the symptomatic management of post-stroke fatigue: A scoping review.

BACKGROUND: Limited medical evidence for managing post-stroke fatigue leads stroke survivors to seek information through other sources. This scoping review aimed to identify and assess the range and quality of web-based recommendations for managing post-stroke fatigue. METHODS: Publicly accessible websites providing advice for post-stroke fatigue management were considered for review using the Joanna Briggs Institute's methodology. Using the search term "fatigue stroke", the first two pages of results from each search engine (Google, Yahoo, and Bing) were assessed against predetermined criteria. Findings were reported in accordance with PRISMA-ScR checklist. Quality and readability were also assessed. RESULTS: Fifty-seven websites were identified; 16 primary and 11 linked websites met the inclusion criteria and demonstrated moderate to high quality and high readability. Primary websites were curated by non-government organizations (n = 10/16), companies (n = 4/16) or were media and blog websites (n = 2/16). Additional resources were provided on linked websites. All websites provided non-pharmacological advice, with four also describing pharmacological management. Many websites included advice related to physical activity modification (n = 18/27) and energy conservation strategies (e.g. activity prioritization, planning, pacing) (n = 26/27). Direction to seek health professional advice appeared frequently (n = 16/27). CONCLUSIONS: The quality of publicly available web-based advice for people with post-stroke fatigue was moderate to high in most websites, with high readability. Energy conservation strategies and physical activity modification appear frequently. The general nature of the advice provided on most websites is supported by direction to healthcare professionals (i.e., clinical referral) who may assist in the practical individualization of strategies for managing post-stroke fatigue.

Organisational survey for acute stroke care in Vietnam: Regional Collaboration Programme.

OBJECTIVES: Low-middle income countries, such as Vietnam have a greater burden from stroke than high-income countries. Few health professionals have stroke specialist training, and the quality of care may vary between hospitals. To support improvements to stroke care, we aimed to gain a better understanding of the resources available in hospitals in Vietnam to manage acute stroke. MATERIALS AND METHODS: The survey questions were adapted from the Australian Organisational Survey of Stroke Services (Stroke Foundation). The final 65 questions covered the topics: hospital size and admissions for stroke; use of clinical protocols and assessments conducted; team structure and coordination; communication and team roles. The survey was distributed electronically or via paper form in Vietnamese to clinical leaders of 91 eligible hospitals (November-December 2020). Data were summarised descriptively. RESULTS: Sixty-six (73%) hospitals responded, and doctors predominately completed the survey (98%). Approximately 70% of hospitals had a stroke unit; median 630 acute strokes/year (IQR: 250-1200) and >90% used stroke clinical protocols. The daytime nurse-patient ratio was 1:4. There was a perceived lack of access to allied health staff, including psychologists/neuropsychologists, occupational therapists, and speech pathologists. Only 50% reported having a standardised rehabilitation assessment process. CONCLUSIONS: This is the first large-scale cross-sectional, national overview of stroke services in Vietnam. Future research should include a systematic clinical audit of stroke care to confirm aspects of the data from these hospitals. Repeating the survey in future years will enable the tracking of progress and may influence capacity building for stroke care in Vietnam.

Stroke in India: A systematic review of the incidence, prevalence, and case fatality.

BACKGROUND: The burden of stroke is increasing in India; stroke is now the fourth leading cause of death and the fifth leading cause of disability. Previous research suggests that the incidence of stroke in India ranges between 105 and 152/100,000 people per year. However, there is a paucity of available data and a lack of uniform methods across published studies. AIM: To identify high-quality prospective studies reporting the epidemiology of stroke in India. SUMMARY OF REVIEW: A search strategy was modified from the Cochrane Stroke Strategy and adapted for a range of bibliographic databases from January 1997 to August 2020. From 7717 identified records, nine studies were selected for inclusion; three population-based registries, a further three population-based registries also using community-based ascertainment and three community-based door-to-door surveys. Studies represented the four cities of Mumbai, Trivandrum, Ludhiana, Kolkata, the state of Punjab, and 12 villages of Baruipur in the state of West Bengal. The total population denominator was 22,479,509 and 11,654 (mean 1294 SD 1710) people were identified with incident stroke. Crude incidence of stroke ranged from 108 to 172/100,000 people per year, crude prevalence from 26 to 757/100,000 people per year, and one-month case fatality rates from 18% to 42%. CONCLUSIONS: Further high-quality evidence is needed across India to guide stroke policy and inform the development and organization of stroke services. Future researchers should consider the World Health Organization STEPwise approach to Surveillance framework, including longitudinal data collection, the inclusion of census population data, and a combination of hospital-registry and comprehensive community ascertainment strategies to ensure complete stroke identification.

Collaborative healthcare education programmes for continuing professional education in low and middle-income countries: A Best Evidence Medical Education (BEME) systematic review. BEME Guide No. 65.

BACKGROUND: Large discrepancies exist between standards of healthcare provision in high-income (HICs) and low and middle-income countries (LMICs). The root cause is often financial, resulting in poor infrastructure and under-resourced education and healthcare systems. Continuing professional education (CPE) programmes improve staff knowledge, skills, retention, and practice, but remain costly and rare in low-resource settings. One potential solution involves healthcare education collaborations between institutions in HICs and LMICs to provide culturally appropriate CPE in LMICs. To be effective, educational partnerships must address the challenges arising from differences in cultural norms, language, available technology and organisational structures within collaborating countries. METHODS: Seven databases and other sources were systematically searched on 7 July 2020 for relevant studies. Citations, abstracts, and studies were screened and consensus was reached on which to include within the review. 54 studies were assessed regarding the type of educational programme involved, the nature of HIC/LMIC collaboration and quality of the study design. RESULTS: Studies varied greatly regarding the types and numbers of healthcare professionals involved, pedagogical and delivery methods, and the ways in which collaboration was undertaken. Barriers and enablers of collaboration were identified and discussed. The key findings were: 1. The methodological quality of reporting in the studies was generally poor. 2. The way in which HIC/LMIC healthcare education collaboration is undertaken varies according to many factors, including what is to be delivered, the learner group, the context, and the resources available. 3. Western bias was a major barrier. 4. The key to developing successful collaborations was the quality, nature, and duration of the relationships between those involved. CONCLUSION: This review provides insights into factors that underpin successful HIC/LMIC healthcare CPE collaborations and outlines inequities and quality issues in reporting.

Etiologic Workup in Cases of Cryptogenic Stroke: A Systematic Review of International Clinical Practice Guidelines.

Background and Purpose- Identifying the etiology of acute ischemic stroke is essential for effective secondary prevention. However, in at least one third of ischemic strokes, existing investigative protocols fail to determine the underlying cause. Establishing etiology is complicated by variation in clinical practice, often reflecting preferences of treating clinicians and variable availability of investigative techniques. In this review, we systematically assess the extent to which there exists consensus, disagreement, and gaps in clinical practice recommendations on etiologic workup in acute ischemic stroke. Methods- We identified clinical practice guidelines/consensus statements through searches of 4 electronic databases and hand-searching of websites/reference lists. Two reviewers independently assessed reports for eligibility. We extracted data on report characteristics and recommendations relating to etiologic workup in acute ischemic stroke and in cases of cryptogenic stroke. Quality was assessed using the AGREE II tool (Appraisal of Guidelines for Research & Evaluation). Recommendations were synthesized according to a published algorithm for diagnostic evaluation in cryptogenic stroke. Results- We retrieved 16 clinical practice guidelines and 7 consensus statements addressing acute stroke management (n=12), atrial fibrillation (n=5), imaging (n=5), and secondary prevention (n=1). Five reports were of overall high quality. For all patients, guidelines recommended routine brain imaging, noninvasive vascular imaging, a 12-lead ECG, and routine blood tests/laboratory investigations. Additionally, ECG monitoring (>24 hours) was recommended for patients with suspected embolic stroke and echocardiography for patients with suspected cardiac source. Three reports recommended investigations for rarer causes of stroke. None of the reports provided guidance on the extent of investigation needed before classifying a stroke as cryptogenic. Conclusions- While consensus exists surrounding standard etiologic workup, there is little agreement on more advanced investigations for rarer causes of acute ischemic stroke. This gap in guidance, and in the underpinning evidence, demonstrates missed opportunities to better understand and protect against ongoing stroke risk. Registration- URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019127822.

Etiologic workup in cases of cryptogenic stroke: protocol for a systematic review and comparison of international clinical practice guidelines.

BACKGROUND: Stroke is a leading cause of death and disability worldwide. Identifying the aetiology of ischaemic stroke is essential in order to initiate appropriate and timely secondary prevention measures to reduce the risk of recurrence. For the majority of ischaemic strokes, the aetiology can be readily identified, but in at least 30% of cases, the exact aetiology cannot be determined using existing investigative protocols. Such strokes are classed as 'cryptogenic' or as a stroke of unknown origin. However, there exists substantial variation in clinical practice when investigating cases of seemingly cryptogenic stroke, often reflecting local service availability and the preferences of treating clinicians. This variation in practice is compounded by the lack of international consensus as to the optimum level and timing of investigations required following a stroke. To address this gap, we aim to systematically review and compare recommendations in evidence-based clinical practice guidelines (CPGs) that relate to the assessment and investigation of the aetiology of ischaemic stroke, and any subsequent diagnosis of cryptogenic stroke. METHOD: We will search for CPGs using electronic databases (MEDLINE, Health Management Information Consortium (HMIC), EMBASE, and CINAHL), relevant websites and search engines (e.g. guideline specific websites, governmental, charitable, and professional practice organisations) and hand-searching of bibliographies and reference lists. Two reviewers will independently screen titles, abstracts and CPGs using a pre-defined relevance criteria form. From each included CPG, we will extract definitions and terms for cryptogenic stroke; recommendations related to assessment and investigation of the aetiology of stroke, including the grade of recommendations and underpinning evidence. The quality of the included CPGs will be assessed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Recommendations across the CPGs will be summarised descriptively highlighting areas of convergence and divergence between CPGs. DISCUSSION: To our knowledge, this will be the first review to systematically compare recommendations of international CPGs on investigating the aetiology of ischaemic stroke. The findings will allow for a better understanding of international perspectives on the optimum level of investigations required following a stroke and thus contribute to achieving greater international consensus on best practice in this important and complex area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019127822.

Does inflammation predispose to recurrent vascular events after recent transient ischaemic attack and minor stroke? The North West of England transient ischaemic attack and minor stroke (NORTHSTAR) study.

BACKGROUND AND HYPOTHESIS: Inflammation is implicated in the pathogenesis and outcome of ischaemic injury. Poststroke inflammation is associated with outcome but it remains unclear whether such inflammation precedes or results from ischaemic injury. We hypothesised that inflammatory markers are associated with an increased risk of recurrent vascular events soon after transient ischaemic attack and minor stroke. METHODS: This was a multicentre, prospective, nested case-control study. Plasma concentrations of C-reactive protein, interleukin-6, interleukin-1-receptor antagonist and fibrinogen, leucocyte counts, erythrocyte sedimentation rate and inflammatory gene allele frequencies were analysed in 711 patients with recent transient ischaemic attack or minor stroke. Cases were defined by the incidence of one or more recurrent vascular events during the three-month follow-up. Association of inflammatory markers with case-status was determined using conditional logistic regression. RESULTS: Plasma concentrations of C-reactive protein, interleukin-1-receptor antagonist and interleukin-6 were not associated with case-status. In secondary analyses, only erythrocyte sedimentation rate was significantly associated with case-status (odds ratio 1·39, 95% confidence interval 1·03-1·85; P=0·03), but this effect did not persist after adjustment for smoking and past history of transient ischaemic attack or stroke. Single nucleotide polymorphisms in four inflammatory genes (interleukin-6, fibrinogen, P-selectin and vascular cell adhesion molecule-1) were nominally associated with case-status. CONCLUSIONS: Circulating inflammatory markers were not associated with recurrent vascular events. Nominally significant associations between genetic markers and case-status will require replication. These data provide little evidence for an inflammatory state predisposing to stroke and other vascular events in a susceptible population.

Brain inflammation is induced by co-morbidities and risk factors for stroke.

Chronic systemic inflammatory conditions, such as atherosclerosis, diabetes and obesity are associated with increased risk of stroke, which suggests that systemic inflammation may contribute to the development of stroke in humans. The hypothesis that systemic inflammation may induce brain pathology can be tested in animals, and this was the key objective of the present study. First, we assessed inflammatory changes in the brain in rodent models of chronic, systemic inflammation. PET imaging revealed increased microglia activation in the brain of JCR-LA (corpulent) rats, which develop atherosclerosis and obesity, compared to the control lean strain. Immunostaining against Iba1 confirmed reactive microgliosis in these animals. An atherogenic diet in apolipoprotein E knock-out (ApoE(-/-)) mice induced microglial activation in the brain parenchyma within 8 weeks and increased expression of vascular adhesion molecules. Focal lipid deposition and neuroinflammation in periventricular and cortical areas and profound recruitment of activated myeloid phagocytes, T cells and granulocytes into the choroid plexus were also observed. In a small, preliminary study, patients at risk of stroke (multiple risk factors for stroke, with chronically elevated C-reactive protein, but negative MRI for brain pathology) exhibited increased inflammation in the brain, as indicated by PET imaging. These findings show that brain inflammation occurs in animals, and tentatively in humans, harbouring risk factors for stroke associated with elevated systemic inflammation. Thus a "primed" inflammatory environment in the brain may exist in individuals at risk of stroke and this can be adequately recapitulated in appropriate co-morbid animal models.

Psychoneuroimmunology of stroke.

Stroke is the major cause of disability in the Western world and is the third greatest cause of death, but there are no widely effective treatments to prevent the devastating effects of stroke. Extensive and growing evidence implicates inflammatory and immune processes in the occurrence of stroke and particularly in the subsequent injury. Several inflammatory mediators have been identified in the pathogenesis of stroke including specific cytokines, adhesion molecules, matrix metalloproteinases, and eicosanoids. An early clinical trial suggests that inhibiting interleukin-1 may be of benefit in the treatment of acute stroke.

Potential surrogate markers of cerebral microvascular angiopathy in asymptomatic subjects at risk of stroke.

Cerebral microvascular angiopathy (MVA) is associated with clinical vascular risk factors and is characterised by histological changes, including thickening of the walls of arterial vessels and dilatation of the Virchow-Robin spaces (VRS). We have previously described two novel biomarkers of MVA based on magnetic resonance imaging (MRI), VRS dilatation and abnormalities in the transfer of systolic arterial pulsation to the ventricular CSF, which occur as a result of decreased cerebral arterial compliance. These are associated with vascular dementia and treatment-resistant late onset depression. We studied a group of normal subjects at risk of cerebrovascular disease to determine if these biomarkers are present in patients who have no evidence of symptomatic vascular disease. We studied 31 subjects, 16 with three or more vascular risk factors and 15 with one or less significant risk factors. We measured arterial blood flow and CSF flow in the cerebral aqueduct, white matter lesion load, and the distribution and number of VRS. There were significant differences in CSF pulsatility and in VRS in the basal ganglia between the two groups, but no differences in white matter lesion load. We conclude that asymptomatic subjects at risk of stroke have MRI evidence of MVA before white matter lesions become apparent.

Interleukin-1 receptor antagonist penetrates human brain at experimentally therapeutic concentrations.

The proinflammatory cytokine interleukin (IL)-1 mediates several forms of experimentally induced acute brain injury and has been implicated in chronic neurodegenerative disorders. The IL-1 receptor antagonist, IL-1RA, protects rodents against ischaemic brain injury, but its molecular mass (17 kDa) potentially limits the brain penetration of peripherally administered IL-1RA. We therefore sought to identify whether therapeutically effective concentrations of IL-1RA in the rat were also achieved in brain of patients with subarachnoid haemorrhage (SAH), using a peripheral administration regime that had proved to be safe and reduce peripheral inflammation in patients after stroke. An intravenous bolus of IL-1RA, followed by infusion, was administered to rats after induction of focal cerebral ischaemia. The effects of IL-1RA on brain ischaemia and the concentrations achieved in cerebrospinal fluid (CSF), were determined. Interleukin-1 receptor antagonist was similarly administered to patients with SAH, and CSF was sampled via external ventricular drains. In rats, IL-1RA significantly reduced brain injury induced by focal cerebral ischaemia. The plasma IL-1RA concentrations reached 12+/-2 microg/mL by 30 mins, and CSF concentrations were maintained between 91 and 232 ng/mL between 1 and 24 h of infusion. In patients with SAH, IL-1RA reached a steady-state plasma concentration of 22+/-4 microg/mL by 15 mins, and CSF concentrations were maintained at 78 to 558 ng/mL between 1 and 24 h. Intravenous delivery of IL-1RA leads to CSF concentrations in patients comparable to those that are neuroprotective in rats, and might therefore be of therapeutic benefit.

Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production.

BACKGROUND: As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS). RESULTS: Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1beta, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-alpha, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5-7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5-7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1beta, TNF-alpha and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol. CONCLUSION: Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS.

Variability of the systemic acute phase response after ischemic stroke.

Despite apparent relationships between ischemic stroke and the acute phase response (APR), considerable variation in the APR exists between individuals. We therefore performed post-hoc analysis of individual APR profiles in 31 patients with ischemic stroke in relation to volume of brain infarction. Patients with ischemic stroke had serial blood samples taken within 12 h, and up to 12 months of symptom onset, for analysis of plasma C-reactive protein (CRP) and interleukin-6 (IL-6). Computed tomography (CT) brain infarct volume was measured at 5 to 7 days (median 23.9 cm(3)). An increase in plasma CRP after the admission sample was evident in 94% of patients by day 5 to 7 (median increase 558% of admission value). CRP response, assessed as area under the curve between admission and day 5 to 7, correlated strongly (r=0.62, p<0.001) with CT infarct volume. Those with greater infarct volumes had more evidence of infection, either prior to or during the first week after stroke. The pattern of response was similar for IL-6, although only 77% showed an increase in plasma IL-6 after the admission sample (median increase 148% of admission value). These data suggest that, although infection and other factors may contribute to systemic inflammation, the extent of acute brain injury after ischemic stroke is a major factor influencing the magnitude and variability of the APR.

Psychoneuroimmunology of stroke.

There is now considerable evidence from both experimental and clinical studies that immune and inflammatory processes can contribute to the onset of stroke and the neurologic and psychologic outcomes. Several specific therapeutic targets have been identified that may significantly improve the devastating impact of stroke.

Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome.

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. METHODS: Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume. RESULTS: Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures. CONCLUSIONS: These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.