Pathophysiology of post-stroke hyperglycaemia and brain arterial patency

RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry

MacDougall, Niall John James ; Muir, Keith W.

University:University of Glasgow

Department:Institute of Neuroscience and Psychology

关键词: stroke, hyperglycaemia, CT, perfusion CT, animal models, met-analysis, human studies, brain arterial patency, CT angiography, acute stroke.;   

Others  :  http://theses.gla.ac.uk/4568/1/2013MacDougallmd.pdf

来源: University of Glasgow

【 摘 要 】

The pathophysiology of acute post-stroke hyperglycaemia (PSH) is important ashyperglycaemia affects the majority of stroke patients, and is consistently associated withpoorer outcome in terms of survival, disability and markers of brain injury such as infarctexpansion. There appears to be an interaction between brain arterial patency andhyperglycaemia that has not been fully characterised.This thesis initially reviews the literature on hyperglycaemia and stroke before focusing onanimal models of PSH and clinical trials of insulin treatment for PSH in two systematicreviews with meta-analysis. The thesis then looks at the relationship between glucoseprofiles and clinical outcome in a historical population receiving IV thrombolysis for acuteischaemic stroke, specifically exploring alternative indices of glycaemic state to comparethe optimal predictive index for functional outcome as measured by the modified Rankinscale.The main body of the thesis details a prospective observational clinical study whichrecruited 108 patients within 6 hours of acute ischaemic stroke. These patients had carefulmonitoring of blood glucose levels over a 48 hour period and detail brain imagingincluding CT perfusion scanning to examine the ischaemic penumbra, CT angiography onadmission and at 24-48 hours to document brain arterial patency with follow-up CT brainimaging to assess outcome infarct volume. The relationship between 48 hour bloodglucose profiles, clinical outcome and imaging findings is then explored.The main findings of the thesis are summarized below.· Animal models of PSH have shown that hyperglycaemia exacerbates infarctvolume in MCA occlusion models but studies are heterogeneous, and do notaddress the common clinical problem of PSH because they have used either thestreptozotocin model of type I diabetes or extremely high glucose loads.· Animal models show that insulin has a non-significant and significantlyheterogeneous effect on infarct growth.3· Clinical trials of insulin for post stroke hyperglycaemia have shown no benefit interms of improved functional outcomes or mortality. Insulin is associated with anincreased risk of hypoglycaemia.· In a historical cohort mean capillary blood glucose over 48 hours was morepredictive of clinical outcome that admission blood glucose or two consecutiveelevated glucose measurements.· A high proportion of acute stroke patients have a blood glucose level above7mmol/L within 6 hours of onset. Different patterns of blood glucose levels definedifferent populations.· Higher admission and mean glucose levels correlate with larger infarct volumes.Larger core perfusion lesion volumes are associated with a greater risk of mortality.Admission hyperglycaemia is more harmful than hyperglycaemia after 6 hours.· In patients with angiographic evidence of an arterial occlusion infarct volumevaries significantly with glycaemic status. In some populations latehyperglycaemia is associated with better imaging outcomes.· Tandem occlusions are associated with bad outcomes after ischaemic stroke.