Neocortical abnormalities of [
            <sup>11</sup>
            C]-flumazenil PET in mesial temporal  lobe epilepsy

Hammers, Alexander; Koepp, MJ; Labbé, Claire; Brooks, David J.; Thom, Maria; Cunningham, Vincent J.; Duncan, John S.

doi:10.1212/wnl.56.7.897

Cited by 101 publications

(50 citation statements)

References 45 publications

(52 reference statements)

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“…However, widespread metabolic abnormalities extending outside the temporal lobe are common in MTLE. 14,21,[35][36][37][38] In this study, the wholebrain SPM analysis appeared to be more appropriate than the ROI method to detect extratemporal restricted foci of hypometabolism without an a priori hypothesis. Recent studies using SPM voxel-based analysis also found an insular involvement, although insular involvement was not highlighted by the authors.…”

Section: Insular Hypometabolism and Bzr Lossmentioning

confidence: 74%

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

Bouilleret

Dupont

Spelle

et al. 2002

Annals of Neurology

103

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Somesthetic and emotional symptoms that are common in patients with mesial temporal lobe epilepsy are usually related to hippocampo-amygdalar complex involvement. Recent stereo-electroencephalographic studies have shown a relationship between such symptoms and epileptic insular discharges. To further investigate this problem, we carried out a positron emission tomography study using fluorodeoxyglucose (18F-FDG) and flumazenil (11C-FMZ) in mesial temporal lobe epilepsy patients. The aim of our study was to assess the existence of a cortical insular involvement in order to examine its clinical correlates and the relationship between the postoperative outcome and the insular involvement. Fluorodeoxyglucose and flumazenil-positron emission tomography studies were carried out in 18 patients with mesial temporal lobe epilepsy patients. A statistical parametric mapping (SPM96) was performed to analyze the data in comparison to 18 healthy volunteers. For each set of fluorodeoxyglucose and flumazenil images a group and an individual analysis were performed. In addition, a region of interest analysis was performed to validate the results. Focusing on the metabolic abnormalities, we also investigated the role of insular cortex in the symptoms experienced by the patients and the prognostic value of insular metabolic abnormalities. Highly significant hypometabolism and BZR binding decreases were detected in the insular cortex. Results were similar using the region of interest approach. Insular involvement (mainly ipsilateral to the seizure focus) was present in 60% of the patients. Emotional symptoms correlated with hypometabolism in the anterior part of the ipsilateral insular cortex, whereas somesthetic symptoms correlated with hypometabolism in the posterior part. No relationship between postoperative outcome and ipsilateral insular hypometabolism was found. Unilateral mesial temporal lobe epilepsy is associated with insular hypometabolism and benzodiazepine receptor loss. Our results also suggest that the anterior part of the insular cortex is involved in the emotional symptoms and the posterior insular cortex is involved in the somesthetic symptoms. Hypometabolism located in the insula did not influence postoperative outcome after anterior lobectomy.

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Section: Insular Hypometabolism and Bzr Lossmentioning

confidence: 74%

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

Bouilleret

Dupont

Spelle

et al. 2002

Annals of Neurology

103

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“…For assessment of medial temporal changes, statistical parametric maps were re-thresholded at P = 0.01 uncorrected, assessed using a medial temporal lobe mask, and significant changes assessed at a threshold of Z > 2.5 and characterized in terms of Z score, extent (k), and coordinates, as described and used previously (Hammers et al, 2001(Hammers et al, , 2002Koepp et al, 1997aKoepp et al, , 1997bKoepp et al, , 2000. This combination of thresholds has a theoretical foundation in the correction for approximately four independent comparisons at the smoothing level of the final SPM (7Z = 2.5 corresponds to a P of 0.0124, that is B0.05/4, a traditional Bonferroni correction for multiple comparisons) and has been empirically validated by approximately yielding the expected false-positive rates in our previous studies.…”

Section: Discussionmentioning

confidence: 99%

[¹¹C]Flumazenil PET in Temporal Lobe Epilepsy: Do We Need an Arterial Input Function or Kinetic Modeling?

Hammers

Panagoda

Heckemann

et al. 2007

J Cereb Blood Flow Metab

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11 C]FMZ PET datasets and arterial plasma input functions were available for 15 patients with medically refractory medial temporal lobe epilepsy (TLE) and histologically verified unilateral HS and for 13 control subjects. SPM2 was used for analysis. ADD1020 and ADD2040 images showed decreased FMZ uptake ipsilateral to the epileptogenic hippocampus in 13/15 cases; 6/13 had bilateral decreases in the ADD1020 analysis and 5/13 in the ADD2040 analysis. BP-SRTM images detected ipsilateral decreases in 12/15 cases, with bilateral decreases in three. In contrast, VD images showed ipsilateral hippocampal decreases in all 15 patients, with bilateral decreases in three patients. Bilateral decreases in the ADD images tended to be more symmetrical and in one case were more marked contralaterally. Full quantification with an image-independent input should ideally be used in the evaluation of FMZ PET; at least in TLE, intrasubject correlations do not predict equivalent clinical usefulness.

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“…Partial volume effect-corrected PET with carbon-11-labeled-flumazenil (FMZ-PET), a marker for the functional integrity of the GABAergic inhibitory neurotransmitter system, is uniquely suited to the study of microdysgenesis in the WM due to its highly specific binding to neurons and the resulting high contrast-tonoise ratio. This elegant technique has shown that in the WM, 11 C-flumazenil binding is strongly related to the number of heterotopic neurons measured semiquantitatively ex vivo in resected specimens of patients who underwent anterior temporal lobe resection [Hammers et al, 2001[Hammers et al, , 2002. Therefore, it is conceivable that our models of blurring mirror increased neuronal heterotopia in this compartment.…”

Section: Interpretation Of Textural Abnormalitiesmentioning

confidence: 96%

Temporal lobe epilepsy: Differential pattern of damage in temporopolar cortex and white matter

Sankar

Bernasconi

Kim

et al. 2008

Human Brain Mapping

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Our purpose was to quantify structural changes of the temporopolar cortex (TPC) and its white matter (TPWM) in temporal lobe epilepsy (TLE) using MRI volumetry and texture analysis. We studied 23 patients with hippocampal atrophy, and 20 healthy controls. Gradient magnitude and entropy were calculated to model signal intensity blurring on T1-MRI. Two observers assessed signal changes and atrophy visually. Compared to controls, TLE patients had a decrease in TPC and TPWM volume ipsilateral to the seizure focus. The gradient magnitude and entropy were decreased ipsilateral to the focus only in TPWM, indicating blurring of this compartment. Eighty-seven percent of TLE patients had at least one volumetric or textural abnormality. Although sensitivity of visual and quantitative assessment of TPC atrophy was comparable (43 and 39%), specificity was higher for volumetry (54% vs. 95%). Compared to visual analysis of signal changes in TPWM on T1-MRI, texture metrics had higher sensitivity (65% vs. 17%) and specificity (100% vs. 69%). The proportion of patients with blurring of TPWM as determined by texture analysis was higher than that seen on visual inspection of T2 images (78% vs. 43%). We found no clear association between volumetric or textural changes of TPC and TPWM and outcome after surgery. Structural changes of the anatomically distinct TPC and TPWM are found ipsilateral to the seizure focus in the majority of TLE patients with hippocampal sclerosis. MRI post-processing allows dissociating different pathological tissue characteristics and shows that atrophy involves gray and white matter, whereas blurring is confined to white matter. Hum Brain

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Neocortical abnormalities of [ ¹¹ C]-flumazenil PET in mesial temporal lobe epilepsy

Cited by 101 publications

References 45 publications

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

[¹¹C]Flumazenil PET in Temporal Lobe Epilepsy: Do We Need an Arterial Input Function or Kinetic Modeling?

Temporal lobe epilepsy: Differential pattern of damage in temporopolar cortex and white matter

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Neocortical abnormalities of [ 11 C]-flumazenil PET in mesial temporal lobe epilepsy

Cited by 101 publications

References 45 publications

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

Insular cortex involvement in mesiotemporal lobe epilepsy: A positron emission tomography study

[11C]Flumazenil PET in Temporal Lobe Epilepsy: Do We Need an Arterial Input Function or Kinetic Modeling?

Temporal lobe epilepsy: Differential pattern of damage in temporopolar cortex and white matter

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Neocortical abnormalities of [ ¹¹ C]-flumazenil PET in mesial temporal lobe epilepsy

[¹¹C]Flumazenil PET in Temporal Lobe Epilepsy: Do We Need an Arterial Input Function or Kinetic Modeling?