ro-16-0154 and Epilepsies--Partial

In the presurgical evaluation of patients with partial epilepsies, the most extensively studied functional neuro-imaging modality to define the origin of seizure onset is fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET). Generally, this technique reveals a widespread zone of interictal glucose hypometabolism in the region of the epileptogenic focus. However, the technique may miss the epileptogenic region and FDG PET abnormalities may extend beyond the seizure onset zone. Consequently, for the precise identification of epileptogenic regions more specific imaging probes than FDG are warranted. This review considers the clinical utility of iomazenil (IMZ) SPET and flumazenil (FMZ) PET for the precise localization of epileptogenic foci in partial epilepsy syndromes.

Topics: Brain; Epilepsies, Partial; Flumazenil; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Iodine Radioisotopes; Radiopharmaceuticals; Receptors, GABA-A; Temporal Lobe; Tomography, Emission-Computed

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

SPECT with the benzodiazepine receptor antagonist 123I-Iomazenil was performed in 33 patients with intractable partial seizures for pre-operative evaluation. The results combined with MRI and 99mTc-HMPAO-SPECT findings were compared with the video-assisted EEG monitoring ("gold standard") which localised the focus in 25 patients. 11 patients underwent surgical resection of the epileptogenic area and became seizure-free for a period up to 13 months. The Iomazenil SPECT had a significantly higher sensitivity compared to 99mTc-HMPAO in the visualization of an epileptogenic area and should be regularly used in the diagnostic of medically intractable partial seizures.

Topics: Adolescent; Adult; Brain; Child; Electroencephalography; Epilepsies, Partial; Female; Flumazenil; Follow-Up Studies; Humans; Iodine Radioisotopes; Male; Middle Aged; Monitoring, Physiologic; Organotechnetium Compounds; Oximes; Postoperative Period; Predictive Value of Tests; Technetium Tc 99m Exametazime; Time Factors; Tomography, Emission-Computed, Single-Photon; Video Recording

After showing in an earlier publication that Iomazenil is a potent benzodiazepine receptor antagonist, the substance has been distributed to 11 clinical centres in Europe for further tests. The protocol asked for volunteers, epileptic cases and patients with Alzheimer's disease. Prior to the Iomazenil examination, flow images by perfusamine or HMPAO were required, and as comparative methods EEG, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. The results allowed first the determination of the normal distribution of the benzodiazepine receptors in the human brain. The highest uptake was found in medial occipital cortex. Second, the evaluation of the epileptic cases shows a 100% positive prediction value for Iomazenil compared to 92% for flow images. Negative prediction values were calculated as 81% for Iomazenil and 54% for flow images. Furthermore, one group reported the successful diagnosis of Alzheimer's disease at an early stage. The visual image examination was tentatively compared to a more objective semiquantitative one based on quotients of corresponding left/right regions of interest. This semiquantitative method has not proved successful yet, but the problems have been identified. A more precise protocol for further studies is therefore proposed.

Topics: Adult; Alzheimer Disease; Brain Chemistry; Epilepsies, Partial; Evaluation Studies as Topic; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

Topics: Adult; Epilepsies, Partial; Female; Flumazenil; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Iodine 123 (I-123) iomazenil is a specific ligand of the central benzodiazepine receptor, which is a part of the postsynaptic gamma-aminobutyric acid A receptor complex. We performed statistical image processing of I-123 iomazenil single-photon emission computed tomography to elucidate maturational changes in the GABAergic system.. Thirty patients (18 boys and 12 girls, aged 17 days to 14 years) with cryptogenic focal epilepsy were enrolled and underwent I-123 iomazenil single-photon emission computed tomography. We used a semiquantitative analytical method consisting of brain surface extraction, anatomic normalization, and a three-parameter exponential model. We then assessed developmental changes in benzodiazepine receptor binding activity in 18 regions of interest in both hemispheres.. The highest benzodiazepine receptor binding activity was observed during early infancy in all regions of interest. Benzodiazepine receptor binding activity then decreased exponentially across development. Benzodiazepine receptor binding in the primary sensorimotor cortex, primary visual cortex, cerebellar vermis, and striatum declined more rapidly than that in the cerebellar hemispheres and the frontal cortex. The pons and the thalamus had the lowest benzodiazepine receptor binding activities during the neonatal period, and benzodiazepine receptor binding in these areas declined gradually after infancy toward adolescence. There were no differences in adjusted benzodiazepine receptor binding activity according to laterality or sex.. Benzodiazepine receptor binding activity decreased exponentially during infancy in all regions of interest. Binding activity in the primary somatosensory and motor cortices (M1 and S1), the primary and association visual areas, the cerebellar vermis, and the striatum (caudate nucleus and putamen) tended to decline more rapidly than that in the cerebellar hemisphere and the frontal association cortex.

Topics: Adolescent; Brain; Brain Mapping; Child; Child, Preschool; Epilepsies, Partial; Female; Flumazenil; Humans; Infant; Infant, Newborn; Iodine Radioisotopes; Male; Radiopharmaceuticals; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

An 11-year-old girl who had been given antiepileptic drugs (AEDs) for occipital lobe epilepsy was hospitalized with alternative psychosis and dysgraphia accompanied by forced normalization of the EEG. Her epileptic seizures and psychosis disappeared after administration of carbamazepine. She developed dysgraphia for Kanji words (Japanese morphograms). The EEG showed sporadic spikes predominantly in the left occipital region, and [123I]iomazenil single-photon-emission computed tomography (IMZ-SPECT) imaging revealed an area of hypoperfusion in the left occipital lobe. Interestingly, the left posterior inferior temporal area is known to play an important role in writing Kanji words. It is assumed that abnormal discharges in the left occipital lobe were projected into the left posterior inferior temporal area and that a functional disorder in that area led to dysgraphia; however, further exploration is needed.

Topics: Agraphia; Anticonvulsants; Carbamazepine; Child; Electroencephalography; Epilepsies, Partial; Female; Flumazenil; Humans; Psychotic Disorders; Tomography, Emission-Computed, Single-Photon

Topics: Adolescent; Adult; Cerebral Cortex; Child; Child, Preschool; Epilepsies, Partial; Female; Flumazenil; Humans; Infant; Male; Tomography, Emission-Computed, Single-Photon; Tuberous Sclerosis

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

We examined the relation between regional 123I-iomazenil (IMZ) parameters and cerebral blood flow (CBF) to evaluate the difference between the quantitative parameters of IMZ and the CBF in detecting epileptic abnormality. Seventeen patients with unilateral partial epilepsy were subjected to 99mTc-hexamethylpropylene amine oxime (HMPAO) SPECT, and early and delayed IMZ SPECT. Then we quantitatively obtained the blood-to-brain transfer constants (K1) and binding potentials (BP) for nine regions of interest, and the regional CBF was also by using the simple angiographic method. From our data, significant asymmetries of BP in the inferior medial temporal lobe and cerebellum were shown and may be related to a remote effect such as crossed cerebellar diaschisis. In conclusion, the asymmetry of BP with iomazenil SPECT was demonstrated in patients with unilateral epilepsy that was not detectable by HMPAO SPECT.

Topics: Adult; Cerebellum; Epilepsies, Partial; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Radiopharmaceuticals; Receptors, GABA-A; Technetium Tc 99m Exametazime; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

The purpose of this study was to compare HMPAO- and IMZ-SPECT findings in treated and untreated patients with focal epilepsies. We examined 20 patients (untreated 13; treated 7). All patients had a normal CT and/or MRI scan. In all patients both whole-brain activity and regional count density (rcd) were evaluated by SPECT. Furthermore, the specific and non-specific binding of IMZ were calculated for each ROI and the results of both, treated and untreated patients were compared. Our data indicate that the normalized cerebral total binding of IMZ was significantly increased in all regions in the group of treated patients (p < 0.001). In contrast, no difference in the tracer binding was found with HMPAO-SPECT. We conclude that the difference in the IMZ-binding might be due either to exogenous or endogenous factors. In our study IMZ-SPECT had a higher sensitivity and a lower specificity in the detection of decreased rcd in areas with EEG findings that indicate an epileptogenic focus compared with HMPAO-SPECT.

Topics: Adolescent; Adult; Epilepsies, Partial; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The distribution of the central benzodiazepine receptor specific ligand iodine-123 iomazenil was investigated in seven human adults from whole-body scans, blood samples and urine collected up to 24 h after injection. Using 12 source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The urinary bladder wall (0.15 mGy/MBq), lower large intestinal wall (0.071 mGy/MBq) testes (0.044 mGy/MBq) and upper large intestined wall (0.038 mGy/MBq) received the highest absorbed doses. The average effective dose equivalent of 123I-IBZM for adults was estimated to be 0.033 mSv/MBq.

Topics: Adult; Epilepsies, Partial; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Radiometry; Radionuclide Imaging; Tissue Distribution

In cortical areas associated with an epileptic focus, there is, in the majority of cases, a correlation between decreased benzodiazepine (Bz) receptor binding, detectable with 123I-Iomazenil, and decreased blood flow. A patient with focal epilepsy due to a localized abnormality in cortical differentiation is presented who showed a marked focal decrease in Bz receptor binding and a normal 99mTc-HMPAO SPECT. Based on this case the relation between blood flow and Bz receptor binding in epileptic foci is discussed.

Topics: Cerebral Cortex; Epilepsies, Partial; Female; Flumazenil; Humans; Iodine Radioisotopes; Middle Aged; Organotechnetium Compounds; Oximes; Receptors, GABA-A; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon