Cerebral misery perfusion diagnosed using hypercapnic blood-oxygenation-level-dependent contrast functional magnetic resonance imaging: a case report

Introduction Cerebral misery perfusion represents a failure of cerebral autoregulation. It is animportant differential diagnosis in post-stroke patients presenting with collapses in the presence of haemodynamically significant cerebrovascular stenosis. This is particularly the case when cortical or internal watershed infarcts are present. When this condition occurs, further investigation should be done immediately. Case presentation A 50-year-old Caucasian man presented with a stroke secondary to complete occlusion of his left internal carotid artery. He went on to suffer recurrent seizures. Neuroimaging demonstrated numerous new watershed-territory cerebral infarcts. No source of arterial thromboembolism was demonstrable. Hypercapnic blood-oxygenation-level-dependent-contrast functional magnetic resonance imaging was used to measure his cerebrovascular reserve capacity. The findings were suggestive of cerebral misery perfusion. Conclusions Blood-oxygenation-level-dependent-contrast functional magnetic resonance imaging allows the inference of cerebral misery perfusion. This procedure is cheaper and more readily available than positron emission tomography imaging, which is the current gold standard diagnostic test. The most evaluated treatment for cerebral misery perfusion is extracranial-intracranial bypass. Although previous trials of this have been unfavourable, the results of new studies involving extracranial-intracranial bypass in high-risk patients identified during cerebral perfusion imaging are awaited. Cerebral misery perfusion is an important and under-recognized condition in which emerging imaging and treatment modalities present the possibility of practical and evidence-based management in the near future. Physicians should thus be aware of this disorder and of recent developments in diagnostic tests that allow its detection.

High glucose mediates prooxidant and antioxidant enzyme activities in coronary endothelial cells

Objective: Excess levels of free radicals such as nitric oxide (NO) and superoxide anion (O2-)are associated with the pathogenesis of endothelial cell dysfunction in diabetes mellitus. This study was designed to investigate the underlying causes of oxidative stress in coronary microvascular endothelial cells (CMEC) exposed to hyperglycaemia. Methods: CMEC were cultured under normal (5.5 mmol/L) or high glucose (22 mmol/L)concentrations for 7 days. The activity and expression (protein level) of eNOS, iNOS, NAD(P)H oxidase and antioxidant enzymes, namely, superoxide dismutase (SOD), catalase and glutahione peroxidase (GPx) were investigated by specific activity assays and Western analyses,respectively while the effects of hyperglycaemia on nitrite and O2 - generation were investigated by Griess reaction and cytochrome C reduction assay, respectively. Results: Hyperglycaemia did not alter eNOS or iNOS protein expressions and overall nitrite generation, an index of NO production. However, it significantly reduced the levels of intracellular antioxidant glutathione by 50% (p<0.05) and increased the protein expressions and/or activities of p22-phox, a membrane-bound component of pro-oxidant NAD(P)H oxidase and antioxidant enzymes (p<0.05). Free radical-scavengers, namely, Tiron and MPG (0.1-1 mol/L) reduced hyperglycaemia-induced antioxidant enzyme activity and increased glutathione and nitrite generation to the levels observed in CMEC cultured in normoglycaemic medium (p<0.01). The differences in enzyme activity and expressions were independent of the increased osmolarity generated by high glucose levels as investigated by using equimolar concentrations of mannitol in parallel experiments. Conclusions: These results suggest that hyperglycaemia-induced oxidative stress may arise in CMEC as a result of enhanced prooxidant enzyme activity and diminished generation of 3 antioxidant glutathione. By increasing the antioxidant enzyme capacity CMEC may protect themselves against free radical-induced cell damage in diabetic conditions. The definitive version is available at http://www.blackwell-synergy.com

Relationship between therapeutic changes in blood pressure and outcomes in acute stroke: a metaregression

Both low and high blood pressure (BP) during the acute phase of stroke are associated independently with a poor outcome. Several small clinical trials have involved the alteration of BP and this study assessed the relationship between change in BP and functional outcome. Randomised controlled trials of interventions that would be expected, on pharmacological grounds, to alter BP in patients within one week of the onset of acute ischaemic or haemorrhagic stroke were sought using electronic searches. Data were collected on BP and clinical outcome. The relationship between the difference in on-treatment BP and odds ratios (OR) for outcomes was assessed using meta-regression. Thirty-seven trials involving 9,008 patients were included. A ‘U’ or ‘J’ shaped relationship were found between on-treatment BP difference and early death, death at the end of 90 day follow up, and combined death or dependency at the end of follow up. Although outcomes were not significantly reduced at any level of change in BP, the lowest odds occurred at: early death (OR 0.87, 95% confidence interval, CI 0.54 to 1.23) - 8.1 mmHg; death at end of follow up (OR 0.96, 95% CI 0.31 to 1.65) - 14.4 mmHg; and combined death or dependency at end of follow up (OR 0.95, 95% CI 0.11 to 1.72) - 14.6 mmHg. Although large falls or increases in BP are associated with a worse outcome, modest reductions may reduce death, and combined death or dependency, although the confidence intervals are wide and compatible with overall benefit or hazard.