Conversion of Ischemic Brain Tissue Into Infarction Increases With Age

Abstract

Background and Purpose-Brain regions normal on diffusion-weighted imaging (DWI) but abnormal on mean transit time (MTT) maps represent tissue at risk of infarction, yet the fate of these regions is quite variable. The imperfect correlation between tissue outcome and initial imaging parameters suggests that each patient's brain may have different susceptibility to ischemic stress. We hypothesize that age is a marker for tissue susceptibility to ischemia and thus plays a role in determining tissue outcome in human stroke. Methods-Sixty patients with acute ischemic stroke and a region of DWI/MTT mismatch that was Ͼ20% of the DWI volume were included. All patients were scanned twice, within 12 hours of symptom onset and on day 5 or later. The percentage mismatch lost (PML) was calculated as percentage of initial DWI/MTT mismatch volume that was infarcted on the follow-up MRI. The statistical analysis explored relationships among the covariates age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtypes, time-to-MRI, and initial DWI, MTT volume, mean arterial blood pressure and blood glucose level at admission, and previous history of hypertension and diabetes mellitus. Results-Univariate comparisons showed that age (Pϭ0.003), hypertension (Pϭ0.009), and diabetes mellitus (Pϭ0.0002)were significantly associated with PML. Regression analyses showed age to be a significant covariate (Pϭ0.02). The regression model predicted a change in PML of Ϸ0.65% per year. The adjusted proportion of variance (R 2 ) in PML that could be explained by age alone was 14%. Conclusion-Age-dependent increase in conversion of ischemic tissue into infarction suggests that age is a biological marker for the variability in tissue outcome in acute human stroke.

Severity of Leukoaraiosis and Susceptibility to Infarct Growth in Acute Stroke

“…Our group has previously shown that age is an independent predictor of PML in a cohort identified from the same prospective data pool used for the present study. 8 There was approximately 50% overlap between study populations of the 2 studies. When the original regression model in this relatively new data set was repeated by removing LA volume from the model, age (Pϭ0.04), DWI volume (Pϭ0.05), and admission blood glucose (Pϭ0.03) appeared to be independent predictors of PML.…”

“…A portion of the study population has been previously published within the context of another study. 8 Patients who had DWI/mean transit time (MTT) mismatch Ͻ20% of the DWI volume, patients who received thrombolytic therapy or investigational drugs, and patients in whom the assessment of final infarct volume was not possible due to extensive hemorrhagic conversion, massive brain edema, or brain surgery (hemicraniectomy) were excluded. The decision to use 20% as a mismatch threshold was based on our unpublished data indicating that the median interexaminer difference for DWI/MTT mismatch measurement was approximately 20%.…”

“…29 Advanced age is a predictor of increased conversion of ischemic tissue into infarction in acute human stroke. 8 Likewise, patients with multiple stroke risk factors are more prone to less favorable outcome after stroke. 30 Thus, there may be no single dominant mechanism by which LA influences tissue outcome and, therefore, it is plausible to presume that LA should be considered as a composite imaging marker for the likelihood of progression of tissue injury in acute stroke due to major cerebral artery occlusion.…”

The impact of aging on spreading depolarization in the intact and ischemic rat brain

“…19D-E). Finally, the age-related metabolic pattern of SD evolution shown here is suggested to substantiate the accelerated conversion of ischemic penumbra into infarction with age, as was described earlier in patients 43 .…”

“…The impact of age on stroke pathophysiology has been the target of intensive research in order to understand the reason for the increased susceptibility of the aged brain to stroke-related injury. Aging was associated with the increased conversion of penumbra into infarction in patients 43 , more severe ischemia-related neurological impairment in old mice, 42 , and accelerated infarct development and neuronal degeneration in old rats 44 . Although SD may be implicated in all these events, the impact of aging on SD evolution, and the potential role SD might play in the age-related worsening of stroke outcome have remained largely unexplored 45 .…”