ro-16-0154 and Epilepsy--Temporal-Lobe

Recent developments of benzodiazepine receptor imaging (123I-Iomazenil SPECT and 11C-Flumazenil PET) in neuropsychiatric disorders were reviewed. In focal epilepsy, a number of previous studies have reported a decreased benzodiazepine receptor binding in epileptic foci and greater sensitivity compared to regional cerebral blood flow imaging, especially for diagnosis of medial temporal lobe epilepsy. These findings indicate clinical validity of benzodiazepine receptor imaging in focal epilepsy and may be related to the "disinhibition mechanism" in GABA/benzodiazepine systems underlying epilepsy. In panic disorder, abnormal benzodiazepine receptor bindings are recently demonstrated in the temporal, parietal or frontal cortex. Further studies would clarify the "benzodiazepine dysfunction hypothesis" in panic disorder.

Topics: Brain; Carbon Radioisotopes; Epilepsy, Temporal Lobe; Flumazenil; Humans; Iodine Radioisotopes; Panic Disorder; Radiopharmaceuticals; Receptors, GABA-A; Reproducibility of Results; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

11C-Flumazenil and 123I-iomazenil are PET and SPECT ligands that bind with high affinity and selectivity to central benzodiazepine receptors. These radiopharmaceuticals are highly suitable for the localization of epileptogenic foci in partial epilepsy. With 11C-flumazenil it is possible to localize epileptogenic foci more accurately than with 18FDG. This PET ligand is also superior to the SPECT ligand and therefore with its increased availability it will possibly become more important in the presurgical assessment of patients with medically intractable temporal and especially extratemporal lobe epilepsy. Due to the high amount of cortical GABAergic synapses, 11C-flumazenil and 123I-iomazenil seem suitable as markers for the integrity of neuronal structure. With the help of these ligands, functionally disturbed areas of the brain can be differentiated from structural changes in patients with cerebral infarcts, cortical dysplasias, traumatic brain lesions or systemic degeneration. Another potential field of clinical use could be the individual pharmacological monitoring of drugs interacting with the GABAA-receptor complex. Imaging of the peripheral-type benzodiazepine receptor seems to be exclusively of scientific interest.

Topics: Brain; Brain Damage, Chronic; Brain Mapping; Cerebral Cortex; Epilepsies, Partial; Epilepsy, Temporal Lobe; Flumazenil; Humans; Image Processing, Computer-Assisted; Iodine Radioisotopes; Receptors, GABA-A; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

The aim of this study was to evaluate the usefulness of (123)I-iomazenil (IMZ) single photon emission computed tomography (SPECT) for the pre-surgical identification of epileptogenic areas in patients with temporal lobe epilepsy and to compare the results with those of (123)I-IMP SPECT and (18)Fluorodeoxyglucose positron emission tomography (FDG PET).. We examined seven patients with medically refractory temporal lobe epilepsy (five men and two women; mean age, 28 years) with no remarkable findings on magnetic resonance imaging. Before surgery, IMZ SPECT, IMP SPECT and FDG PET were all performed in the interictal state. Then, visual assessment and region-of-interest (ROI) analysis were performed on each image. Final definitions of the epileptogenic areas were made by electrocorticography and histopathology.. By IMZ SPECT, a decreased IMZ uptake in the ipsilateral temporal lobe was found in all patients, while a similar decrease in the contralateral temporal lobe was also found in one patient. In comparison to IMP SPECT, the extent of the abnormal area on IMZ SPECT was equal to that on IMP SPECT in one patient while it was more restricted to the epileptogenic area in five patients. In comparison to FDG PET, the extent of the abnormal area on IMZ SPECT was equal to that on FDG PET in three patients while it was more restricted in the epileptogenic area in four patients. In ROI analysis, decreases of IMZ, IMP and FDG uptake were observed in the epileptogenic area, although they were not statistically significant.. IMZ SPECT was considered to be useful for pre-surgical determination of the epileptogenic areas in temporal lobe epilepsy with no remarkable MRI findings, and it was also found to be superior to IMP SPECT and FDG PET for this purpose.

Topics: Adolescent; Adult; Epilepsy, Temporal Lobe; Female; Flumazenil; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Iofetamine; Male; Positron-Emission Tomography; Preoperative Care; Prognosis; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Brain single photon emission computed tomography (SPECT) for epilepsy is divided into two types (using three radionuclide tracers)-perfusion SPECT (123I-IMP or 99 mTc-ECD), identifying epileptogenic foci by detecting abnormality in regional cerebral blood flow, and 123I-iomazenil SPECT, identifying epileptogenic foci based on distribution of central benzodiazepine receptors. This study aimed to statistically evaluate and compare the SPECT effectiveness for the three tracers. Statistical parametric mapping (SPM) analysis was performed on 30 mesial temporal lobe epilepsy (mTLE) patients. The radionuclide and patient data were categorized as follows: abnormality in the medial temporal lobe on the operated hemisphere (AAA), in the entire temporal lobe on the operated hemisphere (AA), in the dominantly affected temporal lobe on the operated hemisphere (A), in bilateral temporal lobes (B), with no abnormalities in bilateral temporal lobes (C), and with abnormality in the temporal lobe on the nonoperated hemisphere (D). For analyses of (AAA), (AA), and (A), examining the hemisphere containing epileptogenic foci, IMP-SPECT was significantly superior to ECD-SPECT (P<0.05). For (AAA), indicating localization, IMZ-SPECT was significantly superior to the other two (P<0.05). IMP-SPECT was superior for lateralizing and IMZ-SPECT was useful for localizing epileptogenic foci in mTLE patients though the applicability of the results in extratemporal lobe epilepsy is unknown.

Topics: Adolescent; Adult; Brain Mapping; Drug Resistance; Epilepsy, Temporal Lobe; Female; Flumazenil; Functional Laterality; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neurosurgical Procedures; Radiopharmaceuticals; Retrospective Studies; Seizures; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Young Adult

To investigate involvement of extrafocal regions in mesial temporal lobe epilepsy (MTLE), we retrospectively explored abnormalities in distribution of iomazenil (IMZ) activity by identifying interhemispheric asymmetry on IMZ-SPECT images of patients with MTLE. Fourteen MTLE patients in whom a good surgical outcome was achieved were included in the study. Voxel-based (VB) analysis and volume-of-interest (VOI) analysis with predefined VOIs were applied to compare IMZ binding between the hemispheres ipsilateral and contralateral to the epileptic focus. VB analysis showed significant decreases in iomazenil binding not only in the ipsilateral anterior temporal lobe including the mesial temporal structures but also in the ipsilateral extratemporal region including the insula, putamen, and medial occipital lobe. VOI analysis showed similar significant decreases in the ipsilateral parahippocampal gyrus, amygdala, putamen, lateral temporal lobe, and lateral occipital lobe. Results of the SPECT analyses suggest that decreased or dysfunctional IMZ activity extends from the mesial temporal lobe to the ipsilateral extrafocal region in patients with MTLE.

Topics: Adult; Epilepsy, Temporal Lobe; Female; Flumazenil; Follow-Up Studies; Functional Laterality; Humans; Iodine Radioisotopes; Male; Tomography, Emission-Computed, Single-Photon; Young Adult

To provide greater accuracy in determining the epileptogenic zone during preoperative evaluation, the authors retrospectively examined 123I-iomazenil single-photon emission computed tomography (IMZ SPECT) studies obtained in patients with temporal lobe epilepsy (TLE) in whom there was no evidence of an abnormality on magnetic resonance (MR) images.. Twelve patients, seven with mesial TLE (MTLE) and five with lateral TLE (LTLE), satisfied the criteria for inclusion in the study. The IMZ SPECT findings in these patients were reviewed retrospectively, and a comparison was made between findings in patients with MTLE and those in patients with LTLE.. The IMZ SPECT studies demonstrated decreased IMZ uptake in the ipsilateral mesial temporal region and the anterobasal temporal lobe in all patients who had MTLE on only one side. On the other hand, IMZ SPECT examinations revealed low IMZ uptake in the ipsilateral lateral temporal lobe in four of five patients with LTLE in whom abnormal findings were restricted to the lateral neocortex. In the remaining patient with LTLE, abnormally low IMZ uptake was found in both mesial and lateral temporal lobes, although pure LTLE was diagnosed by an invasive electroencephalographic evaluation; this patient's habitual seizures continued even after temporal lobectomy, although his mesial structures were spared.. The authors report characteristics of IMZ SPECT findings that differed between patients with MTLE and those with LTLE. The IMZ SPECT examinations proved useful for preoperative evaluation and, to a certain extent, for discrimination between MTLE and LTLE in cases in which MR imaging demonstrated normal findings. The results of this study suggest that IMZ SPECT findings may reflect localization of the epileptogenic zone.

Topics: Adult; Electroencephalography; Epilepsy, Temporal Lobe; Female; Flumazenil; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

Gamma-aminobutyric acid (GABA)-A/benzodiazepine receptors (BZRs) play an important inhibitory role in epileptogenesis. [123I]Iomazenil (123I-IMZ) is a specific ligand for central-type (or neuronal-type) BNRs and is available for single-photon emission computed tomography (SPECT) in brain disorders. We demonstrated alterations of central-type BZRs in human focal epilepsies and their experimental models.. We examined interictal 123I-IMZ SPECT in patients with mesial temporal lobe epilepsy (MTLE; n = 19) with hippocampal sclerosis and neocortical epilepsy with focal cortical dysplasia (NE-CD; n = 18), and compared those with magnetic resonance imaging (MRI) and 123I-IMP SPECT (for regional cerebral blood flow). We also investigated in vitro autoradiography with (123)I-IMZ at various time courses in the intraamygdala kainate, amygdala kindling, and in-utero irradiation models.. In MTLE patients, the epileptogenic hippocampus often showed decreases in both 123I-IMZ and 123I-IMP SPECT. Consistent with those, marked reduction of 125I-IMZ binding was observed in hippocampal CA1-3 regions of the kainate model, which clearly paralleled pyramidal neuronal loss. In contrast, 125I-IMZ binding was increased in the dentate gyrus at 1 month but returned to the normal level at 3-6 months, when frequent spontaneous seizures appeared. The amygdala-kindling model demonstrated similar increases in 125I-IMZ binding in the dentate gyrus without any changes in other brain regions. In NE-CD patients, the epileptogenic foci showed decreased 123I-IMZ binding with relatively normal 123I-IMP SPECT. 125I-IMZ binding also was decreased in the cerebral cortex, hippocampus (areas CA1, 2, and 4), and caudate/putamen of the in-utero irradiation model.. These results indicate that central-type BZRs neuroimaging is useful for detection of epileptogenic foci, but their alterations differ between epilepsy subtypes and time-courses.

Topics: Adult; Amygdala; Animals; Autoradiography; Cerebral Cortex; Dentate Gyrus; Disease Models, Animal; Epilepsies, Partial; Epilepsy, Temporal Lobe; Female; Flumazenil; Hippocampus; Humans; Iodine Radioisotopes; Kainic Acid; Kindling, Neurologic; Magnetic Resonance Imaging; Male; Neocortex; Rats; Receptors, GABA-A; Regional Blood Flow; Tomography, Emission-Computed, Single-Photon

A 26-year-old female with intractable epileptic seizures was studied with I-123 iomazenil cerebral benzodiazepine receptor, I-123 IMP inter-ictal and Tc-99m ECD ictal cerebral blood flow SPECT. The ictal cerebral blood flow SPECT indicated the location of the seizures to be in the left temporal lobe, where increased regional cerebral blood flow was noted in marked contrast to the inter-ictal SPECT. Ictal electroencephalograms (EEGs) recorded with scalp and sphenoidal electrodes also suggested the left temporal lobe as the location of the seizures. On I-123 iomazenil SPECT, however, decreased benzodiazepine receptor density was demonstrated in the right temporal lobe. MRI showed mild atrophy and abnormal signal intensity in the right temporal lobe. Ictal EEGs recorded with intracranial electrodes revealed that abnormal electrical activity of the brain always emerged from the right temporal lobe and then propagated to the contralateral side. Based on the findings of intracranial EEGs, partial resection of the right anterior temporal lobe including hippocampus was performed. After the surgery, no seizure occurred. Pathological examination of the surgical specimens revealed hippocampal sclerosis. This case suggested that cerebral benzodiazepine receptor imaging with I-123 iomazenil can be helpful for correct localization of epileptogenic foci.

Topics: Adult; Brain Mapping; Cerebrovascular Circulation; Epilepsy, Temporal Lobe; Female; Flumazenil; Humans; Radiopharmaceuticals; Receptors, GABA-A; Temporal Lobe; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

To evaluate the changes of the inhibitory neurotransmitter receptor system related to epileptogenesis by measuring central benzodiazepine receptors (BZDRs) in surgically resected specimens of temporal lobe epilepsy by using [(125)I]iomazenil autoradiography.. Surgically resected specimens were obtained from 66 temporal lobe epilepsy patients [51 with mesial temporal lobe epilepsy (MTLE) and 15 with non-MTLE] receiving no BZDs and seven MTLE patients receiving BZDs. BZDR densities in brain sections were measured by using [(125)I]iomazenil autoradiography. Cell densities were measured from cresyl violet-stained sections.. Compared with non-MTLE patients, non-BZD-treated MTLE patients showed remarkable reduction of BZDR density in the pyramidal cell region of cornu ammonis (CA) 1, CA3, and CA4, and a smaller but significant reduction in CA2 and the molecular and granule cell layers of dentate gyrus (mDG). In the MTLE group, the BZDR density in the mDG correlated with that in lateral cortex. Significant correlations between BZDR density and cell density were found in all hippocampal regions. A significant difference in BZDR density/cell-density ratio was observed in CA1 region between MTLE and non-MTLE. BZD-treated patients tended to have lower BZDR densities than did non-BZD-treated patients, although the differences did not reach significance. In all MTLE cases, [(123)I]iomazenil singlephoton emission computed tomography (SPECT) showed decreased BZDR binding in MTL.. In MTLE, BZDR densities decreased parallel to reduction in cell density in most hippocampal subfields, but BZDR density appeared to decrease in excess of neuron loss in CA1. [(125)I]iomazenil SPECT might be useful for detecting in vivo changes of BZDR density.

Topics: Adolescent; Adult; Autoradiography; Benzodiazepines; Cell Count; Child; Child, Preschool; Epilepsy, Temporal Lobe; Female; Flumazenil; Hippocampus; Humans; Iodine Radioisotopes; Male; Receptors, GABA-A; Sclerosis; Temporal Lobe; Tissue Distribution; Tomography, Emission-Computed, Single-Photon

Epileptogenic foci exhibit disturbed function at the level of the benzodiazepine receptor. The aim of our study was to investigate the incidence of focal reductions of temporal benzodiazepine receptor binding (BRB) as assessed by scintigraphy with 123I-iomazenil in patients with denovo temporal lobe epilepsy (TLE).. Forty adult patients (age: 34+/-12 years) with cryptogenic denovo TLE underwent scintigraphy with 123I-iomazenil. In all patients, symptomatic epilepsy was excluded by clinical investigation and MRI. The median duration of TLE was seven months, and the patients had a median of three documented seizures in their history of disease. BRB was quantified in four temporal regions covering the whole temporal lobe. Temporal asymmetry values (ASY) were compared with data determined in 13 age-matched controls yielding Z-scores for global and regional temporal BRB.. A significant reduction of temporal BRB was found in 19 of the 40 patients (48 %), mainly in mesial temporal regions; temporal BRB asymmetries were also found in patients with a short history of seizures and low seizure frequency (< or = 1 year; n = 32, 13/32 (41 %)). Only in the entire cohort did the magnitude of temporal reduction of BRB correlate with the duration of TLE as well as with the number of previous partial seizures (r = 0.40 and r = 0.36; p < 0.03, respectively).. Foci of decreased BRB can already be detected at the onset of TLE; their magnitude is related to ongoing epileptic activity.

Topics: Adolescent; Adult; Binding Sites; Disease Progression; Epilepsy, Temporal Lobe; Female; Flumazenil; Functional Laterality; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Radionuclide Imaging; Receptors, GABA-A; Seizures; Time Factors

To compare published fractional rate constants of I-123-Iomazenil (IMZ) and C-11-Flumazenil (three-compartment/four-parameter model) with a I-123-Iomazenil receptor index calculated from two SPECT acquisitions and to compare the receptor index of the epileptogenic area with the contralateral side in patients with unilateral temporal lobe epilepsies.. 28 patients were studied. 13/28 patients had a drug-resistant unilateral temporal lobe epilepsy with a successful focus localisation performed by an extensive video/EEG monitoring. 15 other patients with clinically suspected focal epilepsy and a normal MRI and IMZ SPECT scanning were used as controls. SPECT scanning was performed in all patients 15 and 100 min after intravenous injection of 111 MBq IMZ and 10 min after application of 740 MBq Tc-99m-HMPAO. Quantification of the regional uptake was performed using ROI-technique and the specific and non-specific binding of IMZ was calculated. The receptor index was calculated by the difference of the specific binding from 15 to 100 min p.i. divided by the time interval.. The receptor index showed a linear correlation with recently published fractional rate constants k3 (r = 0.69 and 0.67; p = 0.15) and a moderate correlation with the k4 constant (-0.53 and -0.43; p = 0.28) by the means of C-11-Flumazenil PET and I-123-Iomazenil SPECT studies, respectively. However, statistical significance was not reached due to the few data points available from the published reports. Furthermore, the IMZ receptor index was lower in the epileptogenic area of patients with unilateral temporal lobe epilepsies compared with their contralateral side (p = 0.02; Wilcoxon-test). The IMZ receptor index showed a weak correlation with the regional cerebral blood flow independent of the evaluated region (r < 0.4; p < 0.05).. The IMZ receptor index indicated to be a simple routine approach to estimate the fractional rate constant k3 (r = 0.67). The lower value of the receptor index within the epileptogenic area might be due to a lower receptor density. However in further studies, IMZ might be a helpful tool to find out subtle changes of the receptor affinity due to its approximately 30-fold higher ligand-receptor affinity compared to C-11-Flumazenil.

Topics: Adult; Brain; Cerebrovascular Circulation; Electroencephalography; Epilepsy, Temporal Lobe; Female; Flumazenil; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Models, Neurological; Radiopharmaceuticals; Receptors, GABA-A; Regression Analysis; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon; Video Recording

Iodine-123 iomazenil (IMZ) has excellent characteristics for the quantification of central benzodiazepine receptor (BZR) binding with single-photon emission tomography (SPET). In order to evaluate the clinical value of IMZ SPET for presurgical identification of epileptic foci in patients with medically intractable seizures, we measured the binding potential (BP) of BZR using two IMZ SPET scans and compared the results with brain perfusion SPET and fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A total of ten patients with intractable partial epilepsy were examined by electroencephalography, magnetic resonance imaging, FDG PET, brain perfusion SPET and IMZ SPET. After neuroimaging examinations, five patients underwent selective surgery, and all of them have since been free of seizures. Two SPET scans were performed at 15 min (early) and 3 h (late) after intravenous injection of 123I-IMZ (167 MBq). Parametric images of the ligand transport (K1) and binding potential (BP) were calculated by the table look-up method, which is based on a three-compartment two-parameter model, using the standard arterial input function obtained by averaging of six normal volunteers' input functions. BP images delineated the epileptic foci more precisely than either FDG PET or ictal perfusion SPET. FDG PET showed widespread reduction, including the area surrounding the focus, and ictal increase in the cerebral blood flow was seen in possibly activated areas spread from the focus. In four epilepsy cases which originated from the mesial temporal lobe without lateral temporal abnormality, there was no significant decrease in the BP images in the lateral temporal structures, which showed decreased uptake of FDG. It is concluded that parametric images of BP with IMZ are valuable for precise presurgical localization of epileptic foci.

Topics: Adult; Brain; Deoxyglucose; Electroencephalography; Epilepsy, Frontal Lobe; Epilepsy, Temporal Lobe; Feasibility Studies; Female; Flumazenil; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Preoperative Care; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures.. Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI.. Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C-flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C-flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non-lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET.. In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery.

Topics: Adolescent; Adult; Carbon Radioisotopes; Deoxyglucose; Electroencephalography; Epilepsy, Temporal Lobe; Female; Flumazenil; Fluorine Radioisotopes; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Preoperative Care; Temporal Lobe; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

The first investigation of the central-type benzodiazepine (BZ) receptor density before and following 2 months successful treatment with carbamazepine (CBZ) in a patient with temporal lobe epilepsy (TLE) using 123I-labelled Iomazenil (a specific lipophile central BZ receptor compound) and single photon emission tomography (SPET) is reported. First, a focal slowing of the EEG in the left temporal area was noted and a corresponding reduction of the central BZ density of the left temporal lobe was found. After 2 months of treatment the patient was symptom-free, and a normal BZ receptor density and no pathological EEG signs were found. The increase in central BZ receptor binding sites might be related to the anticonvulsant effects of CBZ mediated by the so-called peripheral BZ receptor sites.

Topics: Adult; Brain Mapping; Carbamazepine; Epilepsy, Temporal Lobe; Female; Flumazenil; Humans; Image Processing, Computer-Assisted; Radioligand Assay; Receptors, GABA-A; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

We measured the density of two benzodiazepine (BZ) receptor subtypes in neurosurgically obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) showing mesial temporal sclerosis, the most common pathologic finding in TLE. We performed quantitative in vitro receptor autoradiography with [125I]Ro 16-0154, a probe for the central-type BZ receptor and with [3H]PK 11195, a probe for the peripheral-type BZ receptor. In comparison with autopsy and neurosurgical control groups, patients with mesial temporal sclerosis had regionally selective decreased central-type and increased peripheral-type BZ receptors. These changes paralleled regional losses of neurons and proliferation of glia. Decreases of the inhibitory central-type BZ receptor may be a component of the enhanced excitability of the seizure focus and also may allow localization of the focus by in vivo neuroreceptor imaging. Single photon emission computed tomography (SPECT) imaging of two TLE patients with [123I]Ro 16-0154 suggests that this technique may provide a more sensitive means of localizing the seizure focus than current imaging methods relying on changes in blood flow or glucose metabolism.

Topics: Adult; Autoradiography; Epilepsy, Temporal Lobe; Female; Flumazenil; Hippocampus; Humans; Male; Receptors, GABA-A; Sclerosis; Tomography, Emission-Computed, Single-Photon

Fourteen patients with temporal lobe epilepsy, 9 patients after amygdalohippocampectomy and 3 healthy volunteers were examined with the new benzodiazepine receptor marker 123I-Iomazenil and SPECT. For comparison perfusion SPECT studies with 99mTc-HMPAO were done and a quantitative ROI analysis of the data performed. This quantitative analysis consisted of calculation of right-to-left ratios for 123I-Iomazenil SPECTs, whereby values of 1 were obtained with narrow standard deviations. ROI measurements of the medial occipital, frontal and parietal cortex, the cerebellum and white matter showed a pattern of benzodiazepine receptor concentration in concordance with that previously found in PET and autoradiographic studies, if 123I-Iomazenil ROIs were normalized to the corresponding 99mTc-HMPAO ROIs. The abnormal distribution in the temporal lobes will not be discussed in this paper.

Topics: Adult; Aged; Amygdala; Epilepsy, Temporal Lobe; Female; Flumazenil; Hippocampus; Humans; Iodine Radioisotopes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Receptors, GABA-A; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

It was the aim of this study to compare benzodiazepine (Bz) receptor binding and cerebral perfusion in patients with partial epilepsy. Single photon emission tomography (SPET) studies with the flow-marker technetium 99m hexamethylpropylene amine oxine (99mTc-HMPAO) and with the 123I-labelled Bz-receptor ligand Ro 16-0154 (123I-Iomazenil) were performed in 12 patients with partial epilepsy, all with normal magnetic resonance imaging (MRI) and computed tomography (CT) scans. The SPET studies with 123I-Iomazenil were carried out 5 min and 2 h after injection. At 2 h the distribution of activity was very similar to the expected distribution of Bz-receptors in the human brain, known from positron emission tomography (PET) work and post-mortem studies. Early images showed a significantly higher tracer accumulation in the area of the basal ganglia, cerebellum, and naso-pharyngeal space. This finding is caused by non-specific binding and the contribution of the tracer in the blood pool in this phase. Also after 2 h p.i. of 123I-Iomazenil, 9 of the 12 patients showed a focal decrease of of Bz-receptor binding. Ten patients had focal flow abnormalities with 99mTc-HMPAO SPET. In 8 subjects impairment of flow was seen in sites of reduced 123I-Iomazenil uptake. 123I-Iomazenil is suitable for Bz-receptor mapping. In this series of patients, Bz-receptor mapping with SPET seems to offer no advantage over 99mTc-HMPAO in the detection of epileptic foci.

Topics: Adult; Brain; Cerebrovascular Circulation; Epilepsy, Temporal Lobe; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Organotechnetium Compounds; Oximes; Receptors, GABA-A; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

123I-Iomazenil SPECT was performed in 17 patients who were considered candidates for surgery of epilepsy because of medically intractable complex partial seizures. In addition to this examination their presurgical evaluation consisted of long term ictal EEG-CCTV monitoring, CT, MRI and 18FDG PET. In eight patients intracranial ictal EEG recordings were performed. SPECT was assessed visually while PET data were analyzed quantitatively. Both SPECT and PET were compared to ictal EEG data and showed asymmetries in over 80% of patients in agreement with EEG findings. These three methods were in agreement in 65% of patients. SPECT showed abnormality contralateral to the EEG focus in one patient (6%) while PET always demonstrated ipsilateral dysfunction. It is concluded that 123I-Iomazenil SPECT may be considered a more economical and more widely available alternative to 18FDG PET in the presurgical evaluation of patients with medically intractable complex partial seizures. In this respect 123I-Iomazenil specifically reflects functional changes in the membranes of neurons while 18FDG is related to glucose metabolism not only of neurons but also of glial cells.

Topics: Adult; Blood Glucose; Deoxyglucose; Dominance, Cerebral; Electroencephalography; Epilepsy, Temporal Lobe; Evoked Potentials; Female; Flumazenil; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Male; Receptors, GABA-A; Temporal Lobe; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon