Time has been considered to be the prime factor in determining cerebral tissue fate after ischemia. However, severity of ischemia is also an important determinant that may be under appreciated. Animal models have shown that tissue with severely reduced cerebral blood flow (CBF) died while tissues with mild to moderate CBF, defined as 12-18 ml/100g/min, survived. This suggests that the therapeutic window is dependent on the degree of ischemia. This concept has not been examined in humans following ischemic stroke.
The authors conducted a prospective MRI study in acute ischemic stroke patients. Patients were enrolled within 4.5 hours of stroke onset. Acute endovascular intervention was an exclusion criteria. Patients underwent MRI scans at various times: within 4.5 hours, 6 hours, 24 hours, and 1 month following stroke onset. This scan included dynamic susceptibility contrast (DSC) perfusion image which allowed for CBF and CBV calculations. FLAIR sequence at one month was used to determine final tissue fate.
In total, 27 patients were included in the study. 18 patients were treated with IV tPA. 23 patients had perfusion improvement. Perfusion change during the hyperacute phase (3-6 hours) significantly influenced tissue fate regardless of the degrees of ischemia but perfusion change during the acute phase (6-24 hours) impacted tissue outcome only in tissue with mild to moderate ischemia.
An important finding of this study is that perfusion improvement was associated with reduced infarct probability for tissue with mild to moderate ischemia beyond 6 hours suggesting such patients may have a prolonged therapeutic window. The etiology for differing degrees of ischemia was not provided within the study but presumably this was related to collateral circulation. In patients that present later within the 6 hour window for endovascular treatment, CT angiogram and perfusion studies are frequently ordered in order to determine similar parameters as this study. Important limitations of this study include lack of vascular imaging and exclusion of patients with endovascular intervention. Future studies should evaluate outcomes of patients that undergo endovascular treatment beyond 6 hours based on degree of ischemia.
So from this could we calculate the death rate of neurons during the week or so that the neuronal cascade of death is occurring? We never will solve that problems unless we can quantify the neurons dying per minute. 1.9 million neurons dying per minute in stroke focused attention on speed of intervention.