title: Pathophysiology of post-stroke hyperglycaemia and brain arterial patency
Creators: name: MacDougall, Niall John James
Publisher: name: University of Glasgow
Year: 2013
Subjects: subject: stroke, hyperglycaemia, CT, perfusion CT, animal models, met-analysis, human studies, brain arterial patency, CT angiography, acute stroke.

description: The pathophysiology of acute post-stroke hyperglycaemia (PSH) is important as hyperglycaemia affects the majority of stroke patients, and is consistently associated with poorer outcome in terms of survival, disability and markers of brain injury such as infarct expansion. There appears to be an interaction between brain arterial patency and hyperglycaemia that has not been fully characterised. 

This thesis initially reviews the literature on hyperglycaemia and stroke before focusing on animal models of PSH and clinical trials of insulin treatment for PSH in two systematic reviews with meta-analysis. The thesis then looks at the relationship between glucose profiles and clinical outcome in a historical population receiving IV thrombolysis for acute ischaemic stroke, specifically exploring alternative indices of glycaemic state to compare the optimal predictive index for functional outcome as measured by the modified Rankin scale.

The main body of the thesis details a prospective observational clinical study which recruited 108 patients within 6 hours of acute ischaemic stroke. These patients had careful monitoring of blood glucose levels over a 48 hour period and detail brain imaging including CT perfusion scanning to examine the ischaemic penumbra, CT angiography on admission and at 24-48 hours to document brain arterial patency with follow-up CT brain imaging to assess outcome infarct volume. The relationship between 48 hour blood glucose 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 infarct
volume in MCA occlusion models but studies are heterogeneous, and do not
address the common clinical problem of PSH because they have used either the
streptozotocin model of type I diabetes or extremely high glucose loads.

· Animal models show that insulin has a non-significant and significantly
heterogeneous effect on infarct growth.

· Clinical trials of insulin for post stroke hyperglycaemia have shown no benefit in
terms of improved functional outcomes or mortality. Insulin is associated with an
increased risk of hypoglycaemia.

· In a historical cohort mean capillary blood glucose over 48 hours was more
predictive of clinical outcome that admission blood glucose or two consecutive
elevated glucose measurements.

· A high proportion of acute stroke patients have a blood glucose level above
7mmol/L within 6 hours of onset. Different patterns of blood glucose levels define
different 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 volume
varies significantly with glycaemic status. In some populations late
hyperglycaemia is associated with better imaging outcomes.

· Tandem occlusions are associated with bad outcomes after ischaemic stroke.