Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy

Burdette, David E.; Sakurai, Sharin Y.; Henry, Thomas R.; Ross, Donald A.; Pennell, Page B.; Frey, Kirk A.; Sackellares, J. Chris; Albin, Roger L.

doi:10.1212/wnl.45.5.934

Cited by 84 publications

(53 citation statements)

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“…In vitro benzodiazepine binding site analysis in TLE patients demonstrated no decrease in lateral temporal gyri, but in mesial structures binding is correlated with neuronal loss (9). Moreover, immunohistochemical studies show multiple GABA A subunit-specific alterations, including the ␣1-and ␣2-subunits, in the hippocampus of TLE patients (10).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Autoradiographic studies reveal consistent decreases in GABA receptor and cBZR density in the hippocampus but not in the neocortex of temporal lobectomy specimens (19)(20)(21). Further, positron emission tomography (PET) with the cBZR ligand ["Clflumazenil shows that cBZR density consistently is decreased in anterior mesial temporal regions and rarely decreased in temporal neocortex and extratemporal regions in limbic temporal lobe epilepsy (22,23). It is difficult to explain widespread hemispheric asymmetries in amobarbital effect by highly focal hippocampal asymmetries in barbiturate receptor density or affinity.…”

Section: Discussionmentioning

confidence: 99%

Electrocerebral Recovery During the Intracarotid Amobarbital Procedure: Influence of Interval Between Injections

1997

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Summary: Purpose and Methods: During the intracarotid amobarbital procedure (IAP) at the University of Michigan, continuous scalp EEG monitoring guides the timing for presentation of memory items and postinjection testing. Most of our patients have undergone bilateral injections. The interval between injections varied from 22 to 60 min, depending on the test and recovery time, as well as the time to catheterize the second side. After noting a trend toward prolonged electrographic recovery following the second injection, we tested our clinical impression that recovery of the second hemisphere may be influenced by (a) the time between injections and (b) which hemisphere is injected first (epileptogenic or nonepileptogenic).To study these questions, we analyzed EEG recovery data from 48 consecutive IAPs. Approximately half the patients had the epileptogenic side injected first. Results: We found that (a) electrographic recovery after the second injection is prolonged if the interval between bilateral injections is less than 40 minutes and (b) electrographic recovery is more rapid after injection of the epileptogenic hemisphere.Conclusions: We now recommend waiting at least 45 min between injections. The pathophysiology of more prolonged amobarbital effect on the nonepileptogenic hemisphere than on the epileptogenic hemisphere remains unclear. Key Words: Amobarbital-Intracarotid-Epilepsy-Temporal lobeMemory-Epilepsy partial-Injections-Intraarterial.For more than a decade, Wada's intracarotid amobarbital test was used exclusively to localize language function (1). In 1962, Milner (2) proposed that the procedure be used to identify patients at risk for anterograde global amnesia after anterior temporal lobectomy (ATL). While the role of the intracarotid amobarbital procedure (IAP) in localizing language function has remained largely unchanged, significant controversy has arisen about the value of the IAP in (a) noninvasive lateralization of the epileptogenic zone (3-7) and (b) prediction of postoperative memory function (6,8,9). The role of the IAP in predicting both seizure outcome and postoperative cognition depends on consistent, accurate, bilateral memory testing during the procedure. To facilitate investigation of these issues, a standardized IAP protocol, with equivalent injections of the two hemispheres, must be developed. ing the extent of amobarbital effect in the hemisphere contralateral to injection. Previous studies have demonstrated an excellent correlation between the type of online visual analysis we perform and automated quantitative techniques (10). Data available during the IAP provide the most useful information for optimizing the timing of injections and behavioral testing. Qualitative EEG has some additional advantages while the patient is being tested: (a) it allows the electroencephalographer to evaluate different types of artifact effectively (including myogenic, kinesogenic and oculomotor), (b) it allows the electroencephalographer some degree of ability to distinguish between amobarbital-ind...

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“…It is claimed that, because of decreased synaptic activity in the dysplastic epileptogenic cortex, diffuse regional hypometabolism could be seen on FDG-PET scan (45,50,51). With new ligands, such as flumazenil, PET has been shown to identify a more circumscribed site of seizure onset, based on primary histopathologic changes in the epileptogenic area, especially in patients with TLE (52)(53)(54)(55)(56).…”

Section: Discussionmentioning

confidence: 99%

[¹⁸F]FDG‐PET and Whole‐Scalp MEG Localization of Epileptogenic Cortex

et al. 1999

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Summary:Purpose: To evaluate combined [ I 'F]fluorodeoxyglucose ("F-FDG) positron emission tomography (PET) and 122-channel whole-scalp magnetoencephalography (MEG) in lateralizing the epileptogenic cortex in patients whose routine presurgical evaluations gave discordant results about the location of the epileptic focus.Methods: Nine patients (five women, four men) aged 13-40 years were studied. Subdural EEG (SEEG) was recorded from eight patients. Six patients were operated on.Results: In seven of nine patients, PET and MEG agreed in localizing the epileptogenic cortex. When PET and MEG were in congruence, SEEG agreed with the findings. In five of six operated-on patients, PET and MEG results were congruent, and the outcome of the operation was successful. Two patients had discordant PET and MEG results. In one patient, PET showed bitemporal hypometabolism, whereas MEG showed epileptiform activity in the right parietal lobe. The surgical outcome of the palliative temporal lobectomy was poor. Another patient had unilateral temporal hypometabolism in PET and bitemporal activity in MEG. She was not operated on.Conclusions: In most patients, PET and MEG were congruent in locating the epileptogenic cortex. Thus the combination of these techniques may provide useful support for the localization of the seizure onset and reduce the need for invasive procedures. Key Words: [ '8F]FDG-PET-PET-MEGEpilepsy-Epilepsy surgery.Epilepsy surgery has become increasingly common in treating patients with drug-resistant focal epilepsy. Preoperative evaluations are performed to identify the primary epileptogenic zone [i.e, the area of brain tissue necessary and sufficient for the generation of habitual ictal events (l)], to detect the number of additional zones, and to determine their locations with respect to irretrievable cortical areas. Routine preoperative evaluation, with magnetic resonance imaging (MRI), interictal and ictal scalp electroencephalography (EEG), video monitoring, and neuropsychological tests, usually locates the epileptogenic area with reasonable accuracy. However, if the results disagree, invasive ictal EEG recording with subdural (SEEG) or intracerebral electrodes is usually needed to identify the region triggering the seizure. Noninvasive techniques with high sensitivity and specificity are being sought to reduce invasive and timeconsuming procedures in the subgroup of patients with epilepsy and with controversial preoperative evaluation.In patients with temporal lobe epilepsy (TLE), ['sF]fluorodeoxyglucose (FDG) positron emission tomography (PET) usually shows interictal focal decrease of cortical glucose uptake (2-4). FDG-PET indicates regional glucose hypometabolism in 70-89% of patients with TLE, and the congruence with scalp EEG recordings increases to -100% if the MRI is abnormal (5-1 1). PET is already accepted as an essential part of presurgical evaluation in most epilepsy surgery centers (12).Magnetoencephalography (MEG) measures extracranial magnetic fields resulting mainly from electrical currents i...

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Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy

Cited by 84 publications

References 0 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

Electrocerebral Recovery During the Intracarotid Amobarbital Procedure: Influence of Interval Between Injections

[¹⁸F]FDG‐PET and Whole‐Scalp MEG Localization of Epileptogenic Cortex

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Temporal lobe central benzodiazepine binding in unilateral mesial temporal lobe epilepsy

Cited by 84 publications

References 0 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

Electrocerebral Recovery During the Intracarotid Amobarbital Procedure: Influence of Interval Between Injections

[18F]FDG‐PET and Whole‐Scalp MEG Localization of Epileptogenic Cortex

Contact Info

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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

[¹⁸F]FDG‐PET and Whole‐Scalp MEG Localization of Epileptogenic Cortex