Neuroprotection for acute ischemic stroke: Who is most to blame for current failure ?
Neuroprotection has so far proved disappointing in acute ischemic stroke. However, neither clinical nor biological cues of ongoing neurotoxicity were provided in previous phase III trials. Thus it remains unsettled whether faulty drug selection, inadequate patients′ traits, or both, explain treatment failure. In 258 patients with first ever acute hemispheric ischemic stroke we found that admission plasma concentrations of glutamate >200 μmol/L (OR, 26.1; 95%CI, 6.9 to 98.6), interleukin-6 >21.5 pg/mL (OR, 14.9; 95%CI, 4.4 to 50.8), and GABA <190 nmol/L (OR,5.5; 95%CI, 3.2 to 9.7), and NO-metabolites >5.0 μmol/mL in CSF (OR, 5.3; 95%CI, 1.5 to 18.5), were sensitive and specific independent predictors of patients at high-risk of early neurologic deterioration regardless of infarction topography, size, and mechanism. Sensitivity and specificity values are given in the table. Early neurologic deterioration is a harbinger of impending poor outcome that in many instances we could forecast using the aforementioned tests. As early neurologic deterioration most commonly reflects those molecular events that neuroprotectants are aimed to prevent, we advocate to include it as a primary end-point in forthcoming neuroprotectant trials. We also contend to launch large and expensive trials once smaller studies restricted to patients at high-risk of early worsening have disclosed laboratory indications of neuroprotection.