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From the Max-Planck-Institut für neurologische Forschung and
Neurologische Universitätsklinik Köln (Germany).
Correspondence to W.-D. Heiss, MD, Max-Planck-Institut für neurologische Forschung, Gleueler Str 50, D-50931 Köln, Germany.
Background and Purpose—Therapy of
acute ischemic stroke can only be effective as long as neurons
are viable and tissue is not infarcted. Since
Methods—In 10 patients cerebral blood flow, cerebral
metabolic rate for oxygen (CMRO2), oxygen
extraction fraction (OEF), and FMZ binding were studied by positron
emission tomography 3.5 to 16 hours after onset of their first
hemispheric stroke. Early changes in flow, oxygen
metabolism, and FMZ binding were compared with permanent
disturbances in glucose metabolism, and the size of
the final infarcts was determined on MRI or CT 12 to 22 days after the
stroke.
Results—In all patients except one cerebral blood flow 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, inducing highly variable OEF. Areas with markedly decreased
CMRO2 (<60 µmol/100 g per minute) corresponded to
regions with decreased FMZ binding (<4.0 times the mean value in the
white matter). In all patients the final cortical infarcts were visible
on the early FMZ images. Infarcts could be discriminated from
noninfarcted cortex by decreased FMZ binding despite a wide range of
OEF. In finally hypometabolic cortex FMZ binding was
initially decreased or normal, with OEF covering a wide range; 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 injection and regional cerebral blood flow.
Conclusions—These results demonstrate that permanently and
irreversibly damaged cortex can be detected by reduced FMZ binding
early after stroke. Since FMZ distribution additionally images regional
cerebral perfusion, BZR radioligands have a potential as
clinically useful tracers in patients with acute ischemic
stroke. The evidence of tissue damage furnished by these tracers might
be of relevance for the selection of individual therapeutic strategies.
© 1998 American Heart Association, Inc.
Original Contributions
Permanent Cortical Damage Detected by Flumazenil Positron Emission Tomography in Acute Stroke
-aminobutyric acid
receptors are abundant in the cortex and sensitive to ischemic
damage, specific radioligands to their subunits, the
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
[11C]flumazenil (FMZ) early after ischemic stroke
in comparison to the extent of final infarcts and
hypometabolic cortical areas.
Key Words: flumazenil • receptors, benzodiazepine • stroke, ischemic • tomography, emission computed
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