11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI.

Background: Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE).

Objective: To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI.

Methods: Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis.

Cortical dysfunction in non-demented Parkinson's disease patients: a combined (31)P-MRS and (18)FDG-PET study.

Regional cerebral phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) was performed in 10 non- demented Parkinson's disease patients and nine age-matched control subjects. Five of the patients undergoing (31)P-MRS and four additional Parkinson's disease patients had cerebral 2-[(18)F]fluoro-2-deoxy-D-glucose PET ((18)FDG-PET), the results of which were compared with those of eight age-matched control subjects. All Parkinson's disease patients underwent neuropsychological testing including performance and verbal subtests of the Wechsler Adult Intelligence Scale-Revised, Boston Naming Test, Controlled Oral Word Association test (FAS Test) and California Learning Test to exclude clinical dementia.

Reduction of frontal neocortical grey matter associated with affective aggression in patients with temporal lobe epilepsy: an objective voxel by voxel analysis of automatically segmented MRI.

Background: Interictal episodes of aggression are often reported in patients with epilepsy. Some have characteristics of what has been referred to as episodic dyscontrol or intermittent explosive disorder (IED). Although structural brain abnormalities are thought to play a part in the pathophysiology of aggression, there are few in vivo studies of structural cerebral changes in patients with epilepsy and aggression.

Abnormal cerebral structure in juvenile myoclonic epilepsy demonstrated with voxel-based analysis of MRI.

MRI scans of patients with idiopathic generalized epilepsy (IGE) are normal on visual assessment. Using an interactive anatomical segmentation technique and volume-of-interest measurements of MRI, we showed recently that patients with IGE had significantly larger cortical grey matter than control subjects. Further, 40% of individual patients with juvenile myoclonic epilepsy (JME), a syndrome of IGE in adolescence, had significant abnormalities of cerebral structure.

Voxel-by-voxel comparison of automatically segmented cerebral gray matter--A rater-independent comparison of structural MRI in patients with epilepsy.

Quantitative evaluation of MRI in patients with epilepsy can give more information than qualitative assessment. Previously developed volume-of-interest-based methods identified subtle widespread structural changes in the neocortex beyond the visualized lesions in patients with malformations of cortical development (MCD) and hippocampal sclerosis (HS) and also in MRI-negative patients with juvenile myoclonic epilepsy (JME). This study evaluates a voxel-based automated analysis of structural MRI in epilepsy.

Focal cortical release of endogenous opioids during reading-induced seizures.

Background: Studies in animals implicate endogenous release of opioid peptides as a mechanism for terminating partial and generalised seizures. To localise dynamic changes in opioid neurotransmission associated with partial seizures and higher cognitive function, we investigated the release of endogenous opioids in patients with reading-induced seizures compared with healthy controls.

Methods: Five patients who had reading epilepsy and six controls had 11C-diprenorphine (DPN) positron-emission-tomography (PET) scans while reading a string of symbols (baseline) or a scientific paper (activation).

The variants of reading epilepsy. A clinical and video-EEG study of 17 patients with reading-induced seizures.

We present the clinical and electrographic data of 17 patients with reading-induced seizures documented with ictal video-EEG studies during provocation with language related tasks. The median age at onset was 15 years (range 11-22 years) and the male:female ratio was 2.4.

11C-flumazenil PET in neocortical epilepsy.

Objective: To investigate focal cortical abnormalities of gamma-aminobutyric acid type A-central benzodiazepine receptors (GABA(A)-cBZRs) in patients with extratemporal partial seizures with acquired lesions and in patients with normal high-resolution MRI.

Methods: Six patients with acquired lesions and 18 patients with normal high-resolution MRI and extratemporal partial seizures, as well as 24 normal controls, were studied with 11C-flumazenil (FMZ) PET to produce voxel-by-voxel images of FMZ volume of distribution (FMZVD), which reflects density of GABA(A)-cBZRs. These images were analyzed using Statistical Parametric Mapping (SPM).

Cerebral activation in malformations of cortical development.

Malformations of cortical development (MCD) are an important aetiology of localization-related epilepsy. Previous MRI and [11C]flumazenil PET studies have demonstrated widespread structural and neuroreceptor abnormalities beyond the region of MCD that is visually apparent on MRI. We investigated the ability of brain regions affected by MCD to participate in normal cognitive and motor tasks and compared the responses seen in such patients with those in normal subjects.

Evidence for striatal dopamine release during a video game.

Dopaminergic neurotransmission may be involved in learning, reinforcement of behaviour, attention, and sensorimotor integration. Binding of the radioligand 11C-labelled raclopride to dopamine D2 receptors is sensitive to levels of endogenous dopamine, which can be released by pharmacological challenge. Here we use 11C-labelled raclopride and positron emission tomography scans to provide evidence that endogenous dopamine is released in the human striatum during a goal-directed motor task, namely a video game.

In vivo [11C]flumazenil-PET correlates with ex vivo [3H]flumazenil autoradiography in hippocampal sclerosis.

By using [11C]flumazenil-positron emission tomography ([11C]FMZ-PET), we have previously shown that reductions of central benzodiazepine receptors (cBZRs) are restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) caused by unilateral hippocampal sclerosis (HS). Receptor autoradiographic studies on resected hippocampal specimens from the same patients demonstrated loss of cBZRs that was over and above loss of neurons in the CA1 subregion. Here, we report the first direct comparison of in vivo cBZR binding with [11C]FMZ-PET and ex vivo binding using [3H]FMZ autoradiography.

Central benzodiazepine/gamma-aminobutyric acid A receptors in idiopathic generalized epilepsy: an [11C]flumazenil positron emission tomography study.

Purpose: Previous [11C]flumazenil (FMZ) positron emission tomography (PET) investigations in patients with idiopathic generalized epilepsy (IGE) have demonstrated nonsignificant global cortical decreases in central benzodiazepine gamma-aminobutyric acid A (GABA[A]) receptor (cBZR) binding or focal decreases in the thalamus and increases in the cerebellar nuclei with no changes in cerebral cortex. We previously reported lower [11C]FMZ binding in cerebral cortex of IGE patients treated with valproate (VPA) than in cerebral cortex of controls. We now report high-resolution three-dimensional [11C]FMZ PET studies in a larger number of subjects using an improved method to detect differences in cBZR between IGE patients and controls and a more powerful longitudinal design to determine the functional effect of VPA.

Comparison of EEG, MRI and PET in reading epilepsy: a case report.

The pathophysiological and neuroanatomical bases of reading epilepsy (RE) are unclear. We performed video-EEG, high quality MRI and [11C]diprenorphine PET in a patient with RE to detect structural and functional abnormalities. EEG showed multifocal seizure onset bilaterally in temporal and fronto-central regions.

Cortical grey matter and benzodiazepine receptors in malformations of cortical development. A voxel-based comparison of structural and functional imaging data.

Using [11C]flumazenil-PET and statistical parametric mapping (SPM), we have shown recently that regions of increased and decreased benzodiazepine receptor density may be seen in patients with localization-related epilepsy due to malformations of cortical development. These abnormalities were seen both within and beyond lesions visually apparent on high-resolution MRI. We have also shown, using an interactive anatomical segmentation technique and volume-of-interest measurements, that subtle and unsuspected abnormalities of cortical grey matter volume were found in the same group of patients on high-resolution MRI, beyond the lesions visually apparent.

Regional hippocampal [11C]flumazenil PET in temporal lobe epilepsy with unilateral and bilateral hippocampal sclerosis.

Using statistical parametric mapping and [11C]flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis. However, bilateral hippocampal pathology can be present in up to 50% of patients with mesial temporal lobe epilepsy. Additionally, the limited spatial resolution of PET results in a partial volume effect that affects quantitative analysis of cBZRs and such an effect can mask hippocampal dysfunction.

Central benzodiazepine receptor autoradiography in hippocampal sclerosis.

1. The gamma-aminobutyric acid (GABA)A/central benzodiazepine receptor (cBZR) complex is a major inhibitory receptor in the vertebrate CNS. Binding of [11C]-flumazenil to this complex in vivo is reduced in hippocampal sclerosis (HS).

11C-flumazenil PET, volumetric MRI, and quantitative pathology in mesial temporal lobe epilepsy.

Background: Using statistical parametric mapping and 11C-flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) due to hippocampal sclerosis (HS). The limited spatial resolution of PET, however, results in partial-volume averaging that affects quantitative analysis of cBZR density.

Method: We determined hippocampal volume loss and reduction in cBZR binding using an MRI-based method for partial-volume effect correction of 11C-FMZ volume of distribution (FMZ-Vd) in 17 patients with refractory mTLE and an MRI diagnosis of HS that was subsequently histologically verified in all cases.

Cerebral benzodiazepine receptors in hippocampal sclerosis. An objective in vivo analysis.

We objectively delineated the extent of abnormalities in central benzodiazepine receptor (cBZR) binding using [11C]flumazenil (FMZ)-PET and high resolution volumetric MRI in 12 patients with mesial temporal lobe epilepsy (mTLE) associated with unilateral hippocampal sclerosis, who underwent presurgical evaluation and subsequent temporal lobe surgery. We compared parametric 3D-images of regional cerebral [11C]FMZ volume of distribution (Vd) obtained from individuals and groups of patients with [11C]FMZ-Vd from a group of 17 healthy controls using statistical parametric mapping (SPM). The [12C]FMZ-Vd was significantly reduced (P < 0.

Benzodiazepine receptors in focal epilepsy with cortical dysgenesis: an 11C-flumazenil PET study.

Previous imaging studies using 11C-flumazenil in patients with mesial temporal lobe epilepsy and neocortical partial seizure disorders have found focal decreases in gamma-aminobutyric acid type A/benzodiazepine receptor binding. These studies used subjective visual assessment and a region of interest approach to quantitation. We performed three-dimensional, 11C-flumazenil positron emission tomography in 12 patients with cortical dysgenesis identified by high-resolution volumetric magnetic resonance imaging and in 26 normal subjects.

[Benzodiazepine receptor imaging with positron emission tomography and single photon emission tomography].

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.

[Clinical variants of pseudotumor cerebri syndrome].

Increased cerebrospinal fluid pressure of usually unknown etiology is called pseudotumor cerebri. The key symptoms are headache, papilledema and fluctuating visual disturbances. Six cases are presented to illustrate the clinical variability of this syndrome.

Electrocardiographic changes in patients with brain tumors.

Objective: Electrocardiographic (ECG) abnormalities in patients with cerebral tumors involving the limbic system without known organic heart disease.

Design: Retrospective survey.

Setting: A university hospital in Berlin, Germany.

Dystonia in ataxia telangiectasia: report of a case with putaminal lesions and decreased striatal [123I]iodobenzamide binding.

A 6-year-old girl with ataxia telangiectasia and severe progressive dystonic posturing is presented. Magnetic resonance imaging showed cerebellar atrophy and a right-sided putaminal lesion. A single-photon emission computed tomography study of cerebral dopamine-(D2)-receptor binding with [123I]iodobenzamide showed a decreased tracer uptake in the striatum bilaterally.