Planned Ictal FDG PET Imaging for Localization of Extratemporal Epileptic Foci

Meltzer, Carolyn C.; Adelson, P. David; Brenner, Richard P.; Crumrine, Patricia K.; Cott, Anne Van; Schiff, David; Townsend, David W.; Scheuer, Mark L.

doi:10.1111/j.1528-1157.2000.tb00139.x

Cited by 66 publications

(43 citation statements)

References 24 publications

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“…Ictal 18 fluorodeoxyglucose PET imaging has demonstrated a restricted area of focal glucose hypermetabolism in severe partial epilepsy (31), in keeping with the ictal focal hyperperfusion systematically observed in a number of single-photon emission computed tomography studies. A relationship between cerebral glucose metabolism and blood flow is evidenced by the observation of physiologically activity-induced increases in glycolysis producing changes in cytosolic NADH/NAD ϩ ratio that regulates the blood flow in normal human subjects (32).…”

Section: Discussionmentioning

confidence: 80%

Dysfunction of GABA _A receptor glycolysis-dependent modulation in human partial epilepsy

Khallou-Laschet

Kurcewicz

Minier

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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A reduction in GABAergic neurotransmission has been put forward as a pathophysiological mechanism for human epilepsy. However, in slices of human epileptogenic neocortex, GABAergic inhibition can be clearly demonstrated. In this article we present data showing an increase in the functional lability of GABAergic inhibition in epileptogenic tissue compared with nonepileptogenic human tissue. We have previously shown that the glycolytic enzyme GAPDH is the kinase involved in the glycolysis-dependent endogenous phosphorylation of the ␣1-subunit of GABAA receptor, a mechanism necessary for maintaining GABA A function. In human epileptogenic cortex obtained during curative surgery of patients with partial seizures, we demonstrate an intrinsic deficiency of GABA A receptor endogenous phosphorylation resulting in an increased lability of GABAergic currents in neurons isolated from this tissue when compared with neurons from nonepileptogenic human tissue. This feature was not related to a reduction in the number of GABA A receptor ␣1-subunits in the epileptogenic tissue as measured by [ 3 H]flunitrazepam photoaffinity labeling. Maintaining the receptor in a phosphorylated state either by favoring the endogenous phosphorylation or by inhibiting a membrane-associated phosphatase is needed to sustain GABA A receptor responses in epileptogenic cortex. The increased functional lability induced by the deficiency in phosphorylation can account for transient GABAergic disinhibition favoring seizure initiation and propagation. These findings imply new therapeutic approaches and suggest a functional link to the regional cerebral glucose hypometabolism observed in patients with partial epilepsy, because the dysfunctional GABAergic mechanism depends on the locally produced glycolytic ATP.GABAA receptor phosphorylation ͉ GAPDH ͉ human epilepsy ͉ neuronal inhibition P rotein phosphorylation is an important mechanism for the rapid modulation of ion channel properties. Receptorassociated endogenous phosphorylation is required for maintaining the GABA A currents, the principal inhibitory system in the mammalian brain (1, 2). We have identified the kinase of the endogenous phosphorylation as being GAPDH (3), a key glycolytic enzyme. GAPDH is closely associated with the GABA A receptor (GABA A R) macrocomplex at the plasma membrane. GAPDH has a dual role, first as a dehydrogenase in the glycolysis cascade contributing to ATP production and second as a kinase phosphorylating the GABA A R ␣1-subunit (3). All factors promoting the GAPDH-dependent ␣1-phosphorylation also favor the maintenance of the receptor in a functional state, thus directly linking GABAergic inhibition with glucose metabolism. The ␣1-phosphorylation state of the receptor also depends on a membrane-bound phosphatase that is yet to be characterized (4).A wealth of studies have shown that a decrease, even transient, in the efficacy of the GABA A inhibition induces pathological neuronal synchronization resulting in epileptic seizures (5, 6). A deficiency of endogenous GABA A R...

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Section: Discussionmentioning

confidence: 80%

Dysfunction of GABA _A receptor glycolysis-dependent modulation in human partial epilepsy

Khallou-Laschet

Kurcewicz

Minier

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…27 Although none of our subjects had clinically evident seizure activity, the finding in one of the left temporal sharp waves on EEG 2 hours before her second PET scan raises the possibility of nonconvulsive seizure activity as a mechanism of the focally increased FDG uptake. The cortical localization of the increased uptake in 5 of the 6 subjects would be consistent as well.…”

Section: Discussionmentioning

confidence: 99%

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

Zazulia

Videen

2009

Stroke

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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.

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“…The severe group had higher values of jAIj than the mild and moderate groups, and the jAIj was positively correlated with seizure frequency in patients with hyper-or hypometabolism. Although hypermetabolism is frequently observed during the ictal state of epilepsy (32,33), it can also be observed in the absence of ictal events during tracer uptake and correlates well with regions of high spike count, suggesting a state of increased epileptogenicity (33,34). In view of the abundant sample size of patients with interictal hypermetabolism, we assume that the jAIj value on 18 F-FDG PET images in patients with hypermetabolism could be affected by the clinical severity and seizure frequency.…”

Section: Discussionmentioning

confidence: 99%

Glucose Metabolic Profile by Visual Assessment Combined with Statistical Parametric Mapping Analysis in Pediatric Patients with Epilepsy

Zhu

Feng

et al. 2017

J Nucl Med

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PET with 18 F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using 18 F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent 18 F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. 18 F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (jAIj) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of 18 F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The jAIj significantly positively correlated with seizure frequency (P , 0.01) but negatively correlated with the time since last seizure (P , 0.01) in patients with abnormal glucose metabolism. The only significant contributing variable to the jAIj was the time since last seizure, in patients both with hypometabolism (P 5 0.001) and with hypermetabolism (P 5 0.005). For patients with either hypometabolism (P , 0.01) or hypermetabolism (P 5 0.209), higher jAIj values were found in those with drug resistance than with seizure remission. In the post-1-y follow-up PET studies, a significant change of jAIj (%) was found in patients with clinical improvement compared with those with persistence or progression (P , 0.01). Conclusion: 18 F-FDG PET imaging with visual assessment combined with SPM analysis could provide cerebral glucose metabolic profiles in nonsurgical epilepsy patients. jAIj might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic abnormalities on PET. The clinical value of PET might be enhanced by timing the scan closer to clinical seizures.

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Planned Ictal FDG PET Imaging for Localization of Extratemporal Epileptic Foci

Cited by 66 publications

References 24 publications

Dysfunction of GABA _A receptor glycolysis-dependent modulation in human partial epilepsy

Dysfunction of GABA _A receptor glycolysis-dependent modulation in human partial epilepsy

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

Glucose Metabolic Profile by Visual Assessment Combined with Statistical Parametric Mapping Analysis in Pediatric Patients with Epilepsy

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Planned Ictal FDG PET Imaging for Localization of Extratemporal Epileptic Foci

Cited by 66 publications

References 24 publications

Dysfunction of GABA A receptor glycolysis-dependent modulation in human partial epilepsy

Dysfunction of GABA A receptor glycolysis-dependent modulation in human partial epilepsy

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

Glucose Metabolic Profile by Visual Assessment Combined with Statistical Parametric Mapping Analysis in Pediatric Patients with Epilepsy

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Dysfunction of GABA _A receptor glycolysis-dependent modulation in human partial epilepsy

Dysfunction of GABA _A receptor glycolysis-dependent modulation in human partial epilepsy