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Long-term amygdala kindling in rats as a model for the study of interictal emotionality in temporal lobe epilepsy.

Temporal lobe epileptics often experience profound interictal (i.e. between seizure) emotional disturbances, such as fear, anxiety, and depression. Although the presence of this interictal emotionality has been well documented, little progress has been made in identifying its precise nature and cause because it is not amenable to experimental analysis in clinical populations. Accordingly, there is much to gain by studying the fundamental nature and neural basis of interictal emotionality using animal models. Kindling is a widely studied animal model of temporal lobe epilepsy in which daily electrical stimulation of certain brain regions results in the gradual progression and intensification of limbic motor seizures. Several investigators have found that partial and short-term kindling produce robust changes in emotional behavior in both cats and rats. Recently, our laboratory has developed a new model to study interictal emotionality using long-term kindling in rats. These long-term kindled rats display profound changes in fearful and defensive behavior which last for at least two months after the final stimulation. We are now beginning to use this model to study the neural mechanisms underlying the development and expression of interictal emotionality.

Amygdala↗

MRI in the presurgical evaluation of patients with frontal lobe epilepsy and children with temporal lobe epilepsy: pathologic correlation and prognostic importance.

We performed magnetic resonance imaging (MRI) using a high-field strength magnet (1.5 T) in two series of 53 patients with intractable partial epilepsy of frontal lobe or temporal lobe origin who subsequently received ablative surgery for their seizure disorder. In the first series of patients the pathologic correlation and prognostic importance of an MRI-identified lesion in the frontal lobe were assessed. Twenty-five percent of the patients with negative MRI studies and 67% of patients with neuroimaging abnormalities restricted to the frontal lobe, were seizure-free at a minimum duration of follow-up of 1 year. None of the patients with a multilobar MRI-detected abnormality was seizure-free postoperatively. In the second study the sensitivity and specificity of MRI-based hippocampal volumetry was determined in pediatric patients with partial epilepsy of temporal lobe origin unrelated to foreign-tissue pathology. Hippocampal formation atrophy in the epileptic temporal lobe was identified in 63% of patients. The sensitivity and specificity of hippocampal volumetry was 100% in patients with mesial temporal sclerosis. The presence of an MRI-detected epileptogenic lesion in the frontal lobe and hippocampal formation atrophy in the temporal lobe may correlate with the underlying pathology and affect the identification of potential candidates for epilepsy surgery.

Adolescent↗

"Magnetic resonance imaging negative positron emission tomography positive" temporal lobe epilepsy: FDG-PET pattern differs from mesial temporal lobe epilepsy.

PURPOSE: Some patients with temporal lobe epilepsy (TLE) lack evidence of hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would have a different pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with a lateral temporal neocortical rather than mesial focus. PROCEDURES: Thirty consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well-lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and 24 HS+ve patients. Both groups were compared using statistical parametric mapping (SPM), directly and with FDG-PET from 20 healthy controls. RESULTS: Both groups showed lateralized temporal hypometabolism compared to controls. In HS+ve, this was antero-infero-mesial (T = 17.13); in HS-ve the main clustering was inferolateral (T = 17.63). When directly compared, HS+ve had greater hypometabolism inmesial temporal/hippocampal regions (T = 4.86); HS-ve had greater inferolateral temporal hypometabolism (T = 4.18). CONCLUSIONS: These data support the hypothesis that focal hypometabolism involves primarily lateal neocortical rather than mesial temporal structures in 'MRI-negative PET-positive TLE.'

Adult↗

The significance of corpora amylacea in mesial temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) associated with mesial temporal sclerosis (MTS), mesial TLE (MTLE), is the commonest medically refractory adult epilepsy syndrome. Corpora amylacea (CoA) have been shown to be a marker of MTS. We compared 9 patients with MTS who had dense deposition of CoA in their hippocampi with 25 patients with MTS who did not have CoA. The patients with CoA were significantly older and they showed a trend towards having a significantly longer duration of epilepsy. The postoperative seizure outcome at 2 years was not different in the 2 groups. Our results could indicate the progressive nature of the pathology of MTS, probably indicating excitotoxic damage due to recurrent seizures, but they need to be verified by clinicopathological correlation among a larger number of patients with MTLE.

Adult↗

Alumina gel injections into the temporal lobe of rhesus monkeys cause complex partial seizures and morphological changes found in human temporal lobe epilepsy.

The goal of the present study was to determine whether alumina gel injections into temporal lobe structures cause complex partial seizures (CPS) and pathological changes observed in human temporal lobe epilepsy. Rhesus monkeys with alumina gel injections in the amygdala, perirhinal and entorhinal cortices, or Ammon's horn and dentate gyrus all initially displayed focal pathological electroencephalographic (EEG) slowing limited to the site of injection. After clinical seizures developed, they also displayed widespread pathological EEG slowing over both hemispheres, interictal and ictal epileptiform EEG abnormalities limited to the mesial-inferior temporal lobe on the side of injection, and different degrees of spread to other ipsilateral and contralateral structures. Noninjected control and nonepileptic monkeys with injections into the middle and inferior temporal gyri displayed no hippocampal neuronal loss or mossy fiber sprouting. When alumina gel was injected into the amygdala, CPS began within 3-6 weeks and degeneration of neurons and gliosis occurred in the perirhinal cortex or the hippocampus, with consequent sprouting of mossy fibers in the dentate gyrus. Dispersion of the granule cell layer was also observed. Other monkeys with alumina gel in the perirhinal and entorhinal cortices developed CPS within 2-3 weeks after the injections and displayed mossy fiber sprouting only after 4 weeks after the injections. Alumina gel in Ammon's horn and the dentate gyrus also induced CPS, but mossy fiber sprouting was limited to sites immediately adjacent to the injection, probably because none survived more than 4 weeks after the injections. This nonhuman primate model of CPS displayed similar anatomical, behavioral, and EEG features as observed in human temporal lobe epilepsy and provides opportunities to analyze the chronological sequence of epileptogenesis and to test potential therapies.

Aluminum Oxide↗

Seizure-related outcome after corticoamygdalohippocampectomy in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis evaluated by magnetic resonance imaging alone.

OBJECT: The authors conducted a study to assess the efficacy of surgery in patients who underwent magnetic resonance (MR) imaging alone for localization of foci in temporal lobe epilepsy (TLE). METHODS: One hundred patients (43 men, 57 women) with a clinical diagnosis of TLE were prospectively studied (mean age 28 +/- 9 years [+/- standard deviation {SD}]). All patients underwent high-resolution MR imaging, and in all unilateral mesial temporal sclerosis (MTS) was diagnosed by visual inspection. All patients underwent interictal preoperative electroencephalography (EEG) and in 87 patients pre- and 1-year postoperative neuropsychological testing was performed. Both EEG and neuropsychological examinations were conducted in a blinded fashion, and these data were not taken into account during the surgery-related decision-making process. All patients underwent a corticoamygdalohippocampectomy at the side of the MTS. Surgery-related outcome was rated as Class I (seizure free or simple partial seizures only) or Class II (> or = 90% improvement). The follow-up period ranged from 18 to 48 months (mean 24 +/- 5 months [+/-SD]). No patient underwent prolonged video-EEG monitoring, Wada testing, positron emission tomography, or single-photon emission computerized tomography. In eighty-nine patients Class I results were achieved, and 11 Class II results were achieved postoperatively. There was no mortality in this series. Except for in two patients who underwent surgery in the dominant temporal lobe, there was no postoperatively cognitive decline. In these two patients verbal memory decline occurred, which was associated with posterior temporal cortical damage, demonstrated postoperatively on MR imaging. Twenty-five percent of the patients experienced improved memory function related to the nonoperated side, and 54% experienced a 10% gain in general intelligence quotient status. CONCLUSIONS: In patients with clinically suspected TLE, MR imaging alone is able to localize temporal lobe foci correctly. Ruling out pseudoseizures remains the only indication for prolonged video-EEG recordings in this group of patients.

Adult↗

Hyperprolactinemia and temporal lobe epilepsy in a woman: concomitant and persistent prolactin suppression and temporal lobe epilepsy relief.

It has been reported that hyperprolactinemia may be associated with increased temporal lobe activity. Coexisting hyperprolactinemia (97.5 +/- 3.2 ng/ml) related to a pituitary tumefaction (8 mm) and Temporal Lobe Epilepsy (TLE), were observed in a 37-year-old woman. Carbamazepin (CBZ) therapy induced a marked improvement in TLE symptoms and EEG recordings, but did not influence hyperprolactinemia and related symptoms. Long-lasting (27 months) normoprolactinemia (19.4 +/- 0.6 ng/ml) and TLE relief were achieved on a dopamine (DA) agonist medication, e.g. pergolide mesylate, 25-50 micrograms/day given over 8 months, and persisted as long as 27 months after drug withdrawal. Posttreatment CT scans showed progressive shrinkage of the pituitary tumor (2 mm) associated with an empty-sella. It is proposed that, whenever TLE and hyperprolactinemia coexist, therapy with a DA agonist such as pergolide mesylate, resulting in normoprolactinemia, may be beneficial in TLE control.

Adult↗

Temporal lobe epilepsy and neuro-ophthalmology. Ophthalmological findings in 74 temporal lobe resected patients.

A survey is presented of the ophthalmological findings in 74 patients with drug-resistant temporal lobe epilepsy, who underwent unilateral anterior temporal lobectomy 1960-1969 at Rigshospitalet, Copenhagen. At follow-up, 1970-1971, one to ten years following the operation, 81% of the patients had no or only few seizures. Preoperatively 11% of the patients suffered from strabismus as compared to an expected frequency of 5%, but this trend just falls short of statistical significance. The visual acuity remained unchanged in all patients following the operation. Preoperatively a visual field defect was observed in 2 patients. At follow-up 51 patients had homonymous hemianopias, in 38 of them this was limited to the upper quadrants, and in 13 patients also included the lower quandrants, but was characterized as a total homonymous hemianopia in only 6 patients. The presence and extent of the visual field defects were correlated to surgical results, age at onset of epilepsy, age at operation, preoperative duration of epilepsy, presence of grand mal, preoperative complications, and neuropathological findings, but without observing any statistically significant conclusions. On the other hand, the extent of the postoperative visual field defect was significantly influenced by the side of the operation, with more and larger defects following right-sided lobectomies. In the 51 patients with postoperative hemianopias, this defect was either unobserved by the patient or regarded as a considerably less important handicap than the frequent and socially invalidating preoperative seizures...

Adolescent↗

Presurgical evaluation of temporal lobe epilepsy using interictal temporal spikes and positron emission tomography.

OBJECTIVE: Our goal was to determine the role of fludeoxyglucose F 18-positron emission tomography (18FDG-PET) and interictal temporal spikes in lateralizing the epileptogenic region in patients who (1) were diagnosed as having temporal lobe epilepsy based on clinical symptoms and exclusively temporal interictal spikes and (2) did not have a structural lesion on magnetic resonance imaging. DESIGN: This was a retrospective study of 40 consecutive patients fulfilling the above criteria who underwent 18FDG-PET scanning. A firm electrophysiologic diagnosis and 1 complete year of postsurgical follow-up, where applicable, were required. Outcome measures included surgical outcome and final electrophysiologic diagnosis. RESULTS: Unilateral, interictal temporal spikes (ITS) were present in 33 (82.5%) of 40 patients. Seven patients (17.5%) had bitemporal, independent spikes. Thirty-one (77.5%) of 40 patients had unilateral temporal hypometabolism (TH). Twenty-eight (70%) patients had concordant TH and ITS. One year after surgery, 31 of 33 patients with unilateral ITS were greatly improved; two of five who had bitemporal ITS showed similar improvement. In 28 patients, unilateral TH and unilateral ITS were concordant. The paired result always concurred with the final neurophysiologic assessment. Surgical outcome between patients with 18FDG-PET showing unilateral TH (26 of 30 greatly improved) and those not showing unilateral TH (six of eight greatly improved) was not significantly different. CONCLUSION: In temporal lobe epilepsy not associated with a mass lesion, unilateral ITS are reliable lateralizing features and suggest a good surgical outcome. Use of 18FDG-PET provides corroborative lateralizing information but 18FDG-PET that fails to show unilateral TH does not preclude a good surgical outcome.

Action Potentials↗

An MRI-based parcellation method for the temporal lobe.

The temporal lobe has long been a focus of attention with regard to the underlying pathology of several major psychiatric illnesses. Previous postmortem and imaging studies describing regional volume reductions or perfusion defects in temporal subregions have shown inconsistent findings, which are in part due to differences in the definition of the subregions and the methodology of measurement. The development of precise reproducible parcellation systems on magnetic resonance images may help improve uniformity of results in volumetric MR studies and unravel the complex activation patterns seen in functional neuroimaging studies. The present study describes detailed guidelines for the parcellation of the temporal neocortex. It parcels the entire temporal neocortex into 16 subregions: temporal pole, heschl's gyrus, planum temporale, planum polare, superior temporal gyrus (rostral and caudal), middle temporal gyrus (rostral, intermediate, and caudal), inferior temporal gyrus (rostral, intermediate, and caudal), occipitotemporal gyrus (rostral and caudal), and parahippocampal gyrus (rostral and caudal). Based upon topographic landmarks of individual sulci, every subregion was consecutively traced on a set of serial coronal slices. In spite of the huge variability of sulcal topography, the sulcal landmarks could be identified reliably due to the simultaneous display of three orthogonal (transaxial, coronal, and sagittal) planes, triangulated gray matter isosurface, and a 3-D-rendered image. The reliability study showed that the temporal neocortex could be parceled successfully and reliably; intraclass correlation coefficient for each subregion ranged from 0.62 to 0.99. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in the temporal subregions that might reflect underlying neuropathological processes in psychiatric illnesses such as schizophrenia.

Adolescent↗

Characteristics of temporal lobe epilepsy with mesial temporal sclerosis, with special reference to psychotic episodes.

This study investigates the histories and the clinical course of 111 patients who had nonlesional temporal lobe epilepsy. We compared 61 patients with unilateral hippocampal sclerosis (UHS group) and 50 patients with minimal change (MRI negative group) assessed on the basis of MRI. In agreement with previous reports, we confirmed statistically that patients in the UHS group strongly tended to have had febrile convulsive status during early childhood or infancy and that habitual seizures tended to begin at a younger age than the other subset of nonlesional temporal lobe epilepsy. Strikingly, episodes of psychoses, especially postictal psychoses, occurred significantly more often in the UHS group than in the MRI negative group. Additional involvement of temporal neocortex further augmented this association. We stress the role of mesial temporal pathology, and its linkage to the temporal neocortex, in the genesis of postictal psychoses.

Adult↗

Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy.

Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABA(A) receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABA(A) receptor expression and function has an essential role in the process of epileptogenesis.

Animals↗

Gamma-aminobutyric acid uptake is decreased in the hippocampus in a genetic model of human temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most commonly occurring and most intractable forms of seizure disorders in humans. The fundamental mechanisms underlying the pathogenesis of the disorder have, however, not yet been elucidated. El is an inbred mouse strain with genetic predisposition to epileptic seizures. The El mouse epilepsy shares its main features with TLE in humans and is considered to be an excellent model of the latter. We report a marked decrease in the uptake of gamma-aminobutyric acid (GABA) in the hippocampus of El mice. The data favor the involvement of GABA and the hippocampus in the mechanisms of TLE and suggest a genetic basis for the altered GABA uptake. This is the first report suggesting the possibility of a hereditary defect of a neurotransmitter function in TLE.

Animals↗

A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) has a multifactorial etiology involving developmental, environmental, and genetic components. Here, we report a voltage-gated potassium channel gene mutation found in a TLE patient, namely a Kv4.2 truncation mutation. Kv4.2 channels, encoded by the KCND2 gene, mediate A currents in the brain. The identified mutation corresponds to an N587fsX1 amino acid change, predicted to produce a truncated Kv4.2 protein lacking the last 44 amino acids in the carboxyl terminal. Electrophysiological analysis indicates attenuated K+ current density in cells expressing this Kv4.2-N587fsX1 mutant channel, which is consistent with a model of aberrant neuronal excitability characteristic of TLE. Our observations, together with other lines of evidence, raise the intriguing possibility of a role for KCND2 in the etiology of TLE.

Action Potentials↗