Diagnosis of temporal lobe epilepsy by positron emission tomography

Positron emission tomography (PET) was performed in 18 temporal lobe epileptics. About 20 mCi of 11C-glucose was perorally administered to the patients and 30 minutes later scanning was started when the transport of 11C-glucose from blood to the brain tissue reached equilibrium. At the level of 25 mm above orbitomeatal line, the slice image of the temporal lobe shows a relatively high metabolic oval ring involving the amygdala, hippocapal formation and the hippocampal gyrus medially and the T1, T2 and T3 neocortices laterally in normal subjects. The epileptic focus, when detected on PET images, was observed as a defect in this oval ring. In 15(83.3%) out of 18 cases, the location of epileptic focus was confirmed as a low metabolic defect. This diagnosis rate was higher than that of other focal epilepsy by PET study. The locations of foci were divided into three types: mesial (5 cases), lateral (4 cases) and combined (6 cases). The seizure symptoms of the patients were analyzed in terms of the correspondence to the focus types. The results showed that automatism and pseudoabsence had a close relation to the mesial and combined types and psychical, vertiginous or visual seizures correlated to the combined and lateral types. Visceral or motor seizures were induced equally by any focus types. These facts suggested that automatism and pseudoabsence were correlated with the mesial organs such as the amygdala and hippocampus and psychical, vertiginous or visual seizures had origin in lateral neocortices. Visceral or motor seizures were supposed to be the results of the spread from the temporal focus to the adjacent structures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis of temporal lobe epilepsy by positron emission tomography

Temporal lobe epilepsy was studied by the 11C-glucose method of positron emission tomography. The temporal lobe at the level 25 mm above the orbitomeatal line showed the amygdala, hippocampus and hippocampal gyrus medially, and the T1, T2 and T3 neocortices laterally. The focus locations in these structures were divided into mesial, lateral and combined groups on the PECT images. This classification showed a close correlation between the clinical symptoms and the anatomical focus sites.     

Contralateral temporal hypometabolism on positron emission tomography in temporal lobe epilepsy

Introduction — No detailed case studies report lateralised hypometabolism on positron emission tomography (PET) contralateral to the epileptogenic focus in temporal lobe epilepsy (TLE). Material and methods — We performed ¹⁸F fluorodeoxyglucose (FDG) PET in two intractable TLE patients. Results — One had right temporal interictal spikes on electroencephalography (EEG) and a right medial temporal lobe lesion on magnetic resonance imaging (MRI). FDG-PET showed decreased uptake in the left temporal lobe. Right temporal ictal onset, with bilateral interictal epileptiform activity, occurred on intracranial EEG. He is seizure free after right temporal lobectomy and ganglioglioma resection. The second had right temporal lobe interictal and ictal EEG activity. MRI demonstrated right anteriomedial temporal increased T2 signal. Neuropsychology revealed bilateral cognitive dysfunction. FDG-PET showed left anterior temporal and lateral frontal hypometabolism. He is seizure free after right temporal lobectomy. Conclusion — These findings suggest that regional uptake asymmetry on FDG-PET may be give misleading lateralising information in TLE.     

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.     

Hypometabolism and interictal spikes during positron emission tomography scanning in temporal lobe epilepsy

To study the influence of interictal spikes on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), EEG monitoring was performed during PET scanning in 21 patients with temporal lobe epilepsy. Asymmetry indices were calculated in the polar, mesial, anterior-lateral, mid-lateral and posterior-lateral temporal region of interests of FDG-PET (PET-AI). 70.7% of spikes were recorded with their maximum at the anterior temporal region (F(7), F(8), FT(9), FT(10)), 29.3% at mid-temporal (T(7), T(8)), and none at posterior temporal region (P(7), P(8)). Regardless of the side of epileptic focus, right-left difference of the total spikes had a significant negative correlation with right/left PET-AIs of the anterior-lateral temporal region (Spearman's rho = -0.565, p = 0.009), polar (rho = -0.500, p = 0.021) and whole temporal region (rho = -0.480, p = 0.028). FDG-PET hypometabolism may reflect not only a permanent functional deficit but also a transient regional cerebral dysfunction related to the occurrence of interictal spikes.     

Mu-opiate receptors measured by positron emission tomography are increased in temporal lobe epilepsy

Neurochemical studies in animal models of epilepsy have demonstrated the importance of multiple neurotransmitters and their receptors in mediating seizures. The role of opiate receptors and endogenous opioid peptides in seizure mechanisms is well developed and is the basis for measuring opiate receptors in patients with epilepsy. Patients with complex partial seizures due to unilateral temporal seizure foci were studied by positron emission tomography using 11C-carfentanil to measure mu-opiate receptors and 18F-fluoro-deoxy-D-glucose to measure glucose utilization. Opiate receptor binding is greater in the temporal neocortex on the side of the electrical focus than on the opposite side. Modeling studies indicate that the increase in binding is due to an increase in affinity or the number of unoccupied receptors. No significant asymmetry of 11C-carfentanil binding was detected in the amygdala or hippocampus. Glucose utilization correlated inversely with 11C-carfentanil binding in the temporal neocortex. Increased opiate receptors in the temporal neocortex may represent a tonic anticonvulsant system that limits the spread of electrical activity from other temporal lobe structures.     

Accurate prediction of postoperative outcome in mesial temporal lobe epilepsy: a study using positron emission tomography with 18fluorodeoxyglucose

BACKGROUND: Recent studies suggest that positron emission tomography may be a reliable predictive indicator of clinical outcome following surgical treatment for epilepsy. OBJECTIVE: We evaluated 30 patients with documented medial temporal lobe epilepsy to determine if prediction of postoperative outcome is improved with the use of positron emission tomography with (18)fluorodeoxyglucose. PATIENTS AND METHODS: We performed a discriminant analysis to determine the combination of metabolic asymmetry indexes in temporal and extratemporal regions defined by magnetic resonance imaging that best predicted the postoperative outcome. Seizure outcome was assessed at least 2 years after surgery: patients were classified as seizure free (n = 14, group A), mostly improved (n = 10, group B), or as having persistent seizures (n = 6, group C). RESULTS: Discriminant analysis was first performed in groups A and C. The temporal pole seemed to be the only temporal region for which metabolism was a significant predictor of the postoperative outcome (F(1,18) = 10.19; P =.005). The predictive value of positron emission tomography with (18)fluorodeoxyglucose was considerably improved by the multivariate analysis (F(4,15) = 7.21; P =.002), which correctly predicted the 2 -year prognosis in 100% of the patients using 4 regions: the temporal pole, the medial temporal region, the anterior part of the lateral temporal neocortex, and the basofrontal region. As a validation, we performed this 4-region analysis in the patients in group B. The difference among the 3 groups was highly significant (F = 15.5, P<.001). CONCLUSION: These findings suggest that the interictal metabolic pattern reliably predicts the 2-year prognosis after surgery in patients with medial temporal lobe epilepsy.     

Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study

In this study the regional cerebral glucose utilization and the neuropsychological performance of patients with amyotrophic lateral sclerosis (ALS) was investigated. Special attention was given to neuropsychological tests thought to mirror frontal lobe dysfunction. The regional cerebral glucose utilization was studied in 18 patients using high-resolution positron emission tomography. Clinically all patients displayed upper and lower motor neurone signs. In ALS patients glucose metabolism was significantly reduced in the frontal and in the entire cortex compared with controls; no changes were seen in the cerebellum. Comprehensive neuropsychological assessment of ALS patients compared to a pair matched control group revealed mild frontal dysfunction which in part significantly correlated with reduced glucose metabolism in the cortex and subcortical structures. We conclude that in patients with ALS, glucose consumption is decreased in parts of the brain other than the motor cortex accompanied by mild neuropsychological deficits based on the tests employed in this study.     

Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography.

Alterations in a variety of neurotransmitter systems have been identified in experimental models of epilepsy and in brain tissue from patients with intractable temporal lobe seizures. The availability of new high-affinity radioligands permits the study of some neuroreceptors in vivo with positron emission tomography (PET). We previously characterized the in vivo binding of 11C-carfentanil, a potent and selective mu opiate receptor agonist, and described increases in 11C-carfentanil binding in the temporal neocortex of patients with unilateral temporal lobe epilepsy. These studies have been extended to 11C-diprenorphine, which labels mu, kappa, and delta opiate receptor subtypes. Paired measurements of opiate receptor binding were performed with PET using 11C-carfentanil and 11C-diprenorphine in patients with unilateral temporal lobe seizures. Carfentanil binding, reflecting changes in mu opiate receptors, was increased in the temporal neocortex and decreased in the amygdala on the side of the epileptic focus. Diprenorphine binding, reflecting mu as well as non-mu opiate subtypes, was not significantly different among regions in the focus and nonfocus temporal lobes. Regional glucose metabolism, measured using 18F-2-fluoro-2-deoxyglucose, was decreased in the mesial and lateral aspects of the temporal lobe ipsilateral to the epileptogenic focus. The variation in pattern of carfentanil and diprenorphine binding supports a differential regulation of opiate subtypes in unilateral temporal lobe epilepsy.     

Temporal lobe epilepsy presenting as panic attacks: detection of interictal hypometabolism with positron emission tomography.

Cerebral glucose metabolism was studied using positron emission tomography (PET) in a 13-year-old girl with a history of panic attacks that were thought to be of psychiatric origin. Positron emission tomography imaging revealed marked right temporal lobe hypometabolism and magnetic resonance imaging (MRI) detected T2 changes consistent with right mesial temporal sclerosis. Electroencephalogram (EEG) studies 3 years later confirmed a primary diagnosis of right temporal lobe epilepsy. As shown by this case and one other, PET and MRI imaging of patients with panic disorder who are thought to have epilepsy may be helpful in leading to definitive electrographic studies that confirm temporal lobe epilepsy as the primary diagnosis.     

Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an electrophysiologic and volumetric study

PURPOSE: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE. METHODS: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T(1)-weighted three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects. RESULTS: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC-Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec-Hip coupling. CONCLUSIONS: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.     

Different seizure-onset patterns in mesiotemporal lobe epilepsy have a distinct interictal signature

Objective

Experimental research demonstrated that distinct underlying mechanisms go along with different seizure-onset patterns on EEG. These different mechanisms may reflect different tissue abnormalities which, we hypothesize, could also be reflected in morphological differences in the interictal epileptic and background EEG activity.

Alpha-methyl-l-tryptophan positron emission tomography in epilepsy with cortical developmental malformations

Preliminary studies suggest that alpha[(11)C]methyl-l-tryptophan positron emission tomography can detect the epileptic focus within malformations of cortical development. We determined the sensitivity and specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying epileptic focus in children with intractable, neocortical epilepsy with and without malformations of cortical development. Seventy-three epileptic children were classified into lesional and nonlesional groups, and compared regarding focal increased alpha-[(11)C]methyl-l-tryptophan uptake. The sensitivity and specificity of focal increased alpha-[(11)C]methyl-l-tryptophan uptake, using intracranial electroencephalogram localization of seizure onset as the standard, were compared between lesional and nonlesional groups. The specificity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography for detecting seizure onset lobe was equally high in lesional (97%) and nonlesional groups (100%), whereas sensitivity was higher in the lesional than the nonlesional group (47% versus 29%; P = 0.047). The incidence of alpha-[(11)C]methyl-l-tryptophan uptake abnormality was higher in the lesional than the nonlesional group (P < 0.01). Alpha-[(11)C]methyl-l-tryptophan positron emission tomography localized and visualized epileptogenic regions in 25% of patients with nonlocalizing magnetic resonance imaging. Although overall sensitivity of alpha-[(11)C]methyl-l-tryptophan positron emission tomography in identifying neocortical epileptic focus is modest, specificity is extremely high. When an alpha-[(11)C]methyl-l-tryptophan focus is detected, it likely represents the epileptogenic region to be resected.     

Thyrotoxic autoimmune encephalopathy: a repeat positron emission tomography study

Thyroid related autoantibodies have been related to the development of encephalopathy, known as Hashimoto's encephalopathy. However, their relation with the encephalopathy occurring in patients with Graves' disease has not been well established. The case is reported of a 51 year old woman presenting with subacute progressive dementia with evidence of hyperthyroidism. She had Graves' disease associated with high titres of thyroid related autoantibodies. Her encephalopathy was not improved by antithyroid drugs, but promptly responded to corticosteroid treatment, and stabilised with a gradual reduction of thyroid related autoantibody titres. Brain positron emission tomography initially showed a diffuse and multifocal cerebral hypometabolism with subsequent normalisation on her clinical recovery, which was consistent with the acute and reversible cerebral inflammation probably mediated by autoimmune mechanisms.     

Glucose and [11C]flumazenil positron emission tomography abnormalities of thalamic nuclei in temporal lobe epilepsy

OBJECTIVES: To analyze interictal patterns of thalamic nuclei glucose metabolism and benzodiazepine receptor binding in patients with medically intractable temporal lobe epilepsy (TLE) using high-resolution 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET. BACKGROUND: Structural and glucose metabolic abnormalities of the thalamus are considered important in the pathophysiology of TLE. The differential involvement of various thalamic nuclei in humans is not known. METHODS: Twelve patients with TLE underwent volumetric MRI, FDG and FMZ PET, and prolonged video-EEG monitoring. Normalized values and asymmetries of glucose metabolism and FMZ binding were obtained in three thalamic regions (dorsomedial nucleus [DMN], pulvinar, and lateral thalamus [LAT]) defined on MRI and copied to coregistered, partial-volume-corrected FDG and FMZ PET images. Hippocampal and amygdaloid FMZ binding asymmetries and thalamic volumes also were measured. RESULTS: The DMN showed significantly lower glucose metabolism and FMZ binding on the side of the epileptic focus. The LAT showed bilateral hypermetabolism and increased FMZ binding. There was a significant correlation between the FMZ binding asymmetries of the DMN and amygdala. The PET abnormalities were associated with a significant volume loss of the thalamus ipsilateral to the seizure focus. CONCLUSIONS: Decreased [11C]flumazenil (FMZ) binding and glucose metabolism of the dorsomedial nucleus (DMN) are common and have strong lateralization value for the seizure focus in human temporal lobe epilepsy. Decreased benzodiazepine receptor binding can be due to neuronal loss, as suggested by volume loss, but also may indicate impaired gamma-aminobutyric acid (GABA)ergic transmission in the DMN, which has strong reciprocal connections with other parts of the limbic system. Increased glucose metabolism and FMZ binding in the lateral thalamus could represent an upregulation of GABA-mediated inhibitory circuits.     

Temporoparietal cortex in aphasia. Evidence from positron emission tomography

Forty-four aphasic patients were examined with (F18)-fluorodeoxyglucose positron emission tomography in a resting state to determine whether consistent glucose metabolic abnormalities were present. Ninety-seven percent of subjects showed metabolic abnormalities in the angular gyrus, 89% in the supramarginal gyrus, and 87% in the lateral and transverse superior temporal gyrus. Pearson product moment correlations were calculated between regional metabolic measures and performance on the Western Aphasia Battery. No significant correlations were found between the Western Aphasia Battery scores and right hemisphere metabolic measures. Most left hemisphere regions correlated with more than one score from the Western Aphasia Battery. Temporal but not frontal regions had significant correlations to the comprehension score. The left temporoparietal region was consistently affected in these subjects, suggesting that common features in the aphasias were caused by left temporoparietal dysfunction, while behavioral differences resulted from (1) the extent of temporoparietal changes, and (2) dysfunction elsewhere in the brain, particularly the left frontal and subcortical areas.