PERMANENT CORTICAL DAMAGE DETECTED BY FLUMAZENIL POSITRON-EMISSION-TOMOGRAPHY IN ACUTE STROKE

Background and Purpose-Therapy of acute ischemic stroke can only be ef fective as long as neurons are viable and tissue is not infarcted. Sin ce gamma-aminobutyric acid receptors are abundant in the cortex and se nsitive to ischemic damage, specific radioligands to their subunits, t he central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [C-11]flumaze nil (FMZ) early after ischemic stroke in comparison to the extent of f inal infarcts and hypometabolic cortical areas. Methods-In 10 patients cerebral blood now, cerebral metabolic rate for oxygen (CMRO2), oxyge n extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemisph eric stroke. Early changes in now, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and t he size of the final infarcts was determined on MRI or CT 12 to 22 day s after the stroke. Results-In all patients except one cerebral blood now was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits . In these areas CMRO2 was also reduced but to a variable degree, indu cing highly variable OEF. Areas with markedly decreased CMRO2 (<60 mu mol/100 g per minute) corresponded to regions with decreased FMZ bindi ng (<4.0 times the mean value in the white matter). In all patients di e final cortical infarcts were visible on the early FMZ images. Infarc ts could be discriminated from noninfarcted cortex by decreased FMZ bi nding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide r ange; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after i njection and regional cerebral blood flow. Conclusions-These results d emonstrate that permanently and irreversibly damaged cortex can be det ected by reduced FMZ binding early after stroke. Since FMZ distributio n additionally images regional cerebral perfusion, BZR radioligands ha ve a potential as clinically useful tracers in patients with acute isc hemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic str ategies.