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Pippa J Tyrrell

Publications and source records attributed to Pippa J Tyrrell.

9 recordsLinked to original sources
PubMed2006

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.

Acute-Phase Reaction↗
PubMed2005

Interleukin-1 and neuronal injury.

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.

Animals↗
PubMed2004

Reliability of a semi-automated technique of cerebral infarct volume measurement with CT.

BACKGROUND: A reliable method of infarct volume measurement is needed if infarct volume is to be used as an outcome measure in clinical stroke trials. We investigated the reproducibility of a semi-automated method of computed tomography (CT) infarct volume measurement amongst three stroke research fellows with no formal neuroradiology training and two consultant neuroradiologists. METHODS: CT brain scans for volumetric analysis were performed at 5 to 7 days in 34 patients with acute ischaemic stroke, of which 28 scans showed visible recent infarction. Five observers independently traced the infarct boundary on digitised images with a cursor. Volumetric analysis incorporated pixel thresholding with preset Hounsfield thresholds. One of the observers repeated the analyses on 21 of the scans in order to assess intraobserver variation. RESULTS: Median infarct volume was 35.7 cm3 (range 0.2-318 cm3). The closest limits of observed agreement (mean +/- 1.96 SD) between pairs of observers were between a research fellow and neuroradiologist (-29 to 21 cm3). The widest limits of agreement were between a different research fellow and the same neuroradiologist (-39.1 to 41.4 cm3). The limits of agreement between infarct volumes measured on two separate occasions by one of the research fellows were -7 to 8 cm3. CONCLUSIONS: Intraobserver reliability of CT infarct volume measurements performed by a stroke research fellow was superior to interobserver reliability between any pair of observers. The wide limits of agreement between different observers using manual tracing may not be acceptable in multicentre trials of acute ischaemic stroke treatment, but volume measurement by a single observer appears to be more reliable.

Aged↗
PubMed2004

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.

Aged↗
PubMed2003

An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis.

Central nervous system and peripheral inflammation is important in the responses to ischaemic stroke, and may also predispose to its development. We aimed to identify (1) the extent to which a peripheral inflammatory response is activated in patients following acute stroke, and (2) whether there was evidence for preexisting peripheral inflammation. Thirty-six patients with ischaemic stroke within 12 h of onset of symptoms had serial blood samples taken up to 12 months for analysis of markers of inflammation. Thirty-six control subjects, individually matched for age, sex and degree of atherosclerosis, were also studied. Median C-reactive protein (CRP) was elevated, relative to controls (2.08 mg/l), from admission (4.31 mg/l) (p</=0.001) until 3 months (2.90 mg/l) (p</=0.01), the greatest elevation occurring at 5-7 days (17.67 mg/l) (p</=0.001). Elevations were also seen in erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count until 3 months. Median plasma IL-6 was also elevated, relative to controls (9 pg/ml), by 24 h after onset of symptoms (22 pg/ml) (p</=0.01), and remained elevated at 5-7 days (23 pg/ml) (p</=0.01), but not at 3 months. Less marked elevations in these markers were seen in patients without evidence of infection except for IL-6, which was not increased in the absence of infection. These data provide evidence of an early and sustained peripheral inflammatory response to acute ischaemic stroke in patients with or without evidence of infection. The very early increase in concentrations of inflammatory markers after stroke may either be induced by stroke itself, or may indicate a preexisting inflammatory condition in stroke patients which may contribute to the development of stroke.

Acute Disease↗
PubMed2002

Poststroke shoulder pain: a prospective study of the association and risk factors in 152 patients from a consecutive cohort of 205 patients presenting with stroke.

BACKGROUND AND PURPOSE: Shoulder pain is known to retard rehabilitation after stroke. Its causes and prognosis are uncertain. This study describes the incidence of poststroke shoulder pain prospectively, in an unselected stroke population in the first 6 months after stroke and identifies risk factors for developing pain. METHODS: 297 patients with possible stroke were screened and stroke diagnosed in 205 cases. The 152 patients entered the study of which 123 patients were assessed up to 6 months. This cohort, with a mean age of 70.6 years, was examined at 2 weeks, 2, 4, and 6 months. A history of shoulder pain, Barthel score, anxiety and depression score were recorded. Full neurological and rheumatological examination was undertaken, using the contralateral side as a control. Pain outcome and stroke outcome was recorded at subsequent visits. RESULTS: 52 (40%) patients developed shoulder pain on the same side of their stroke. There was a strong association between pain and abnormal shoulder joint examination, ipsilateral sensory abnormalities and arm weakness. Shoulder pain had resolved or improved at 6 months in 41 (80%) of the patients with standard current treatment. CONCLUSIONS: Shoulder pain after stroke occurred in 40% of 123 patients surviving, consenting and not too unwell to participate. This included 52 patients of an original cohort of 205 patients presenting with stroke. Eighty percent of patients made a good recovery with standard treatment Patients with sensory and or motor deficits represent at risk sub-groups.

Adult↗
PubMed2002

Inflammation and infection in clinical stroke.

Stroke has enormous clinical, social, and economic implications, and demands a significant effort from both basic and clinical science in the search for successful therapies. Atherosclerosis, the pathologic process underlying most coronary artery disease and the majority of ischemic stroke in humans, is an inflammatory process. Complex interactions occur between the classic risk factors for atherosclerosis and its clinical consequences. These interactions appear to involve inflammatory mechanisms both in the periphery and in the CNS. Central nervous system inflammation is important in the pathophysiologic processes occurring after the onset of cerebral ischemia in ischemic stroke, subarachnoid hemorrhage, and head injury. In addition, inflammation in the CNS or in the periphery may be a risk factor for the initial development of cerebral ischemia. Peripheral infection and inflammatory processes are likely to be important in this respect. Thus, it appears that inflammation may be important both before, in predisposing to a stroke, and afterwards, where it is important in the mechanisms of cerebral injury and repair. Inflammation is mediated by both molecular components, including cytokines, and cellular components, such as leukocytes and microglia, many of which possess pro- and/or antiinflammatory properties, with harmful or beneficial effects. Classic acute-phase reactants and body temperature are also modified in stroke, and may be useful in the prediction of events, outcome, and as therapeutic targets. New imaging techniques are important clinically because they facilitate dynamic evaluation of tissue damage in relation to outcome. Inflammatory conditions such as giant cell arteritis and systemic lupus erythematosus predispose to stroke, as do a range of acute and chronic infections, principally respiratory. Diverse mechanisms have been proposed to account for inflammation and infection-associated stroke, ranging from classic risk factors to disturbances of the immune and coagulation systems. Considerable opportunities therefore exist for the development of novel therapies. It seems likely that drugs currently used in the treatment of stroke, such as aspirin, statins, and modulators of the renin-angiotensin-aldosterone system, act at least partly via antiinflammatory mechanisms. Newer approaches have included antimicrobial and antileukocyte strategies. One of the most promising avenues may be the use of cytokine antagonism, for example, interleukin-1 receptor antagonist.

Brain Ischemia↗