Transient Focal Increase in Perihematomal Glucose Metabolism After Acute Human Intracerebral Hemorrhage

Abstract

Background and Purpose-Progressive perihematomal cell death over 3 to 4 days has been described after experimental intracerebral hemorrhage (ICH). We investigated whether progressive perihematomal damage occurs in human subjects by measuring relative changes in regional cerebral glucose metabolism with 18 F-fluorordeoxyglucose (FDG) positron emission tomography at multiple time points during the first week after ICH. Methods-Thirteen subjects with a median hematoma volume of 22 cm 3 were studied 1.0Ϯ0.3, 2.9Ϯ0.8, and 6.7Ϯ1.6 days after ICH. Normalized mean counts in 5 concentric annular 2-mm-thick perihematomal volumes-of-interest (VOIs) were compared to the initial study. Next, automated searches with 0.5 to 5.0 mL spherical VOIs identified maximum focal changes in normalized counts compared to the initial study. Results-No annular or focal decrease in perihematomal FDG uptake developed. Instead, FDG uptake significantly increased at session #2 in the first 3 2-mm annular VOIs (9.2%Ϯ14.2, 7.8%Ϯ11.3, 5.9%Ϯ9.0), returning to baseline at session #3. The VOI search identified focal regions of increased perihematomal FDG uptake relative to the contralateral control hemispheres in 6 subjects, which accounted for the annular increase. Conclusion-Perihematomal glucose metabolism increased transiently in a subset of patients 2 to 4 days after acute ICH.These transient focal increases in glucose metabolism occurring in the brain after acute ICH demonstrate that there are ongoing processes in response to injury that last for days. Although further studies are needed to elucidate their pathophysiology, these processes may be indicative of a prolonged window for intervention to improve neurological outcome.

Temporal Pattern of Cytotoxic Edema in the Perihematomal Region After Intracerebral Hemorrhage

“…6 Accumulated evidence suggests a nonischemic metabolic crisis surrounding the hematoma. [7][8][9] Brain tissue samples of patients who had been operated on within 72 hours after ICH showed mitochondrial dysfunction in the perihematomal region, 7 which was thought to contribute to a reduction in oxidative metabolism and the use of oxygen in this region. 8 A transient focal increase in perihematomal glucose metabolism was observed 2 to 4 days postictus and resolved on day 7.…”

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention

“…14, 154 The mechanism of focally increased glucose uptake may be due to nonconvulsive seizure activity, which is found in many patients with acute ICH. 131 These repetitive depolarizations may lead to secondary injury by increasing extracellular glutamate, resulting in intracellular calcium accumulation and excitotoxicity.…”

Experimental Intracerebral Hemorrhage: Avoiding Pitfalls in Translational Research

“…Of note, in the acute setting the majority of patients with ICH are unsuitable for magnetic resonance imaging due to medical instability (Singer et al, 2004). Though sophisticated imaging studies can be successfully performed in such patients (Zazulia et al, 2009), this requires a very well set up and staffed service to conduct such research safely and to obtain useable and reliable data. Such difficulties therefore limit what can be achieved in the clinical setting.…”