SEARCH · PubMed Health

Results for “TLE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed2001

Neuronal hypertrophy in the neocortex of patients with temporal lobe epilepsy.

The underlying cause of neocortical involvement in temporal lobe epilepsy (TLE) remains a fundamental and unanswered question. Magnetic resonance imaging has shown a significant loss in temporal lobe volume, and it has been proposed that neocortical circuits are disturbed functionally because neurons are lost. The present study used design-based stereology to estimate the volume and cell number of Brodmann's area 38, a region commonly resected in anterior temporal lobectomy. Studies were conducted on the neocortex of patients with or without hippocampal sclerosis (HS). Results provide the surprising finding that TLE patients have significant atrophy of neocortical gray matter but no loss of neurons. Neurons are also significantly larger, dendritic trees appear sparser, and spine density is noticeably reduced in TLE specimens compared with controls. The increase in neuronal density we found in TLE patients is therefore attributable to large neurons occupying a much smaller volume than in normal brain. Neurons in the underlying white matter are also increased in size but, in contrast to other reports, are not significantly elevated in number or density. Neuronal hypertrophy affects HS and non-HS brains similarly. The reduction in neuropil and its associated elements therefore appears to be a primary feature of TLE, which is not secondary to cell loss. In both gray and white matter, neuronal hypertrophy means more perikaryal surface area is exposed for synaptic contacts and emerges as a hallmark of this disease.

Adolescent↗

PubMed2001

[Clinical study on epileptic aura in children with temporal lobe epilepsy].

We studied the clinical characteristics of epileptic aura with temporal lobe epilepsy (TLE) in children, by retrospectively reviewing medical records of 33 patients whose first seizures developed under 15 years of age. The diagnosis of TLE was made by interictal EEG and head MRI/SPECT, both of which demonstrated a temporal lesion. The patients were classified into 24 with mesial TLE syndrome, 3 with a temporal lobe tumor, 3 with temporal lobe dysplasia and 3 with other causes. The epileptic aura was not recognized in 5 patients (15%). The age at onset of aura ranged from 4 to 10 years with a median age at 7. In patients older than 10, it was always followed by impairment of consciousness. It was manifested with nausea in 14 patients (42%), vertigo, a sense of fear, palpitation and heating sensation on the back in three patients (9%) each. Thus, clinical manifestations of epileptic aura in children with TLE were largely identical to those of adult patients. Detailed history taking about the aura may provide a clue to the diagnosis of TLE even in children.

Adolescent↗

PubMed2003

Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus.

Changes in the expression of ion channels, contributing to altered neuronal excitability, are emerging as possible mechanisms in the development of certain human epilepsies. In previous immature rodent studies of experimental prolonged febrile seizures, isoform-specific changes in the expression of hyperpolarization-activated cyclic nucleotide-gated cation channels (HCNs) correlated with long-lasting hippocampal hyperexcitability and enhanced seizure susceptibility. Prolonged early-life seizures commonly precede human temporal lobe epilepsy (TLE), suggesting that transcriptional dysregulation of HCNs might contribute to the epileptogenic process. Therefore, we determined whether HCN isoform expression was modified in hippocampi of individuals with TLE. HCN1 and HCN2 expression were measured using in situ hybridization and immunocytochemistry in hippocampi from three groups: TLE with hippocampal sclerosis (HS; n = 17), epileptic hippocampi without HS, or non-HS (NHS; n = 10), and autopsy material (n = 10). The results obtained in chronic human epilepsy were validated by examining hippocampi from the pilocarpine model of chronic TLE. In autopsy and most NHS hippocampi, HCN1 mRNA expression was substantial in pyramidal cell layers and lower in dentate gyrus granule cells (GCs). In contrast, HCN1 mRNA expression over the GC layer and in individual GCs from epileptic hippocampus was markedly increased once GC neuronal density was reduced by >50%. HCN1 mRNA changes were accompanied by enhanced immunoreactivity in the GC dendritic fields and more modest changes in HCN2 mRNA expression. Furthermore, similar robust and isoform-selective augmentation of HCN1 mRNA expression was evident also in the pilocarpine animal model of TLE. These findings indicate that the expression of HCN isoforms is dynamically regulated in human as well as in experimental hippocampal epilepsy. After experimental febrile seizures (i.e., early in the epileptogenic process), the preserved and augmented inhibition onto principal cells may lead to reduced HCN1 expression. In contrast, in chronic epileptic HS hippocampus studied here, the profound loss of interneuronal and principal cell populations and consequent reduced inhibition, coupled with increased dendritic excitation of surviving GCs, might provoke a "compensatory" enhancement of HCN1 mRNA and protein expression.

Adolescent↗

PubMed2005

Metabolite phantom correction of the nonuniform volume-selection profiles in MR spectroscopic imaging: application to temporal lobe epilepsy.

BACKGROUND AND PURPOSE: In MR spectroscopic imaging (MRSI), the volume-selection profiles of metabolites differ from each other. These differences cause variations in metabolite intensities, which are particularly prominent when the hippocampi are evaluated. We hypothesize that the errors arising from these effects cause notable artifact when temporal lobe epilepsy (TLE) is lateralized with MRSI. METHODS: We examined a metabolite phantom, control subjects, and patients with TLE by using MRSI. We calculated the error arising from the different volume-selection profiles of metabolites in vitro and evaluated this correction in the examination of the control subjects and in the lateralization of epilepsy in the patients. RESULTS: Without a correction, a considerable error in the metabolite content existed, even deep inside the spectroscopic volume of interest. The result was false asymmetry (P < .008) in the hippocampi of control subjects. Among the 11 patients, TLE was correctly lateralized in three only after the correction was made, and in one, TLE was incorrectly lateralized. CONCLUSION: The volume-selection profiles of N-acetylaspartate, choline, and creatine differ enough to cause a significant error, even in the metabolite ratios, when patients with TLE are examined with MRSI. We propose a simple phantom method to correct for this error without a need to modify the pulse sequence.

Adolescent↗

PubMed2005

5-HT 1A receptors are reduced in temporal lobe epilepsy after partial-volume correction.

UNLABELLED: Preclinical studies suggest that serotonin 1A receptors (5-HT 1A) play a role in temporal lobe epilepsy (TLE). Previous PET studies reported decreased 5-HT 1A binding ipsilateral to epileptic foci but did not correct for the partial-volume effect (PVE) due to structural atrophy. METHODS: We used PET with 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY), a 5-HT 1A receptor antagonist, to study 22 patients with TLE and 10 control subjects. In patients, 18F-FDG scans also were performed. An automated MR-based partial-volume correction (PVC) algorithm was applied. Psychiatric symptoms were assessed with the Beck Depression Inventory Scale. RESULTS: Before PVC, significant (uncorrected P < 0.05) reductions of 18F-FCWAY binding potential (BP) were detected in both mesial and lateral temporal structures, mainly ipsilateral to the seizure focus, in the insula, and in the raphe. Group differences were maximal in ipsilateral mesial temporal regions (corrected P < 0.05). After PVC, differences in mesial, but not lateral, temporal structures and in the insula remained highly significant (corrected P < 0.05). Significant (uncorrected P < 0.05) BP reductions were also detected in TLE patients with normal MR images (n = 6), in mesial temporal structures. After PVC, asymmetries in BP remained significantly greater than for glucose metabolism in hippocampus and parahippocampus. There was a significant inverse relation between the Beck Depression score and the ipsilateral hippocampal BP, both before and after PVC. CONCLUSION: Our study shows that in TLE patients, reductions of 5-HT 1A receptor binding in mesial temporal structures and insula are still significant after PVC. In contrast, partial-volume effects may be an important contributor to 5-HT 1A receptor-binding reductions in lateral temporal lobe. Reduction of 5-HT 1A receptors in the ipsilateral hippocampus may contribute to depressive symptoms in TLE patients.

Adult↗

PubMedDate not supplied

[Impact of experience on improving the surgical outcome in temporal lobe epilepsy].

INTRODUCTION: Recently, we have published the results of a first surgical series of patients with temporal lobe epilepsy (TLE). We describe a posterior series of patients intervened of TLE, we compare the functional results with the previous series and we finally analyze the causes of changes. PATIENTS AND METHODS: We studied the first 22 consecutive patients surgically intervened of TLE with a minimum post-surgery follow-up of 2 years. Patients showing I and II Engel's grade were used as gold standard for evaluation of pre-surgical complementary studies. RESULTS: We have obtained better functional results: 91% patients showing Engel's grade I, 9% showing grade II and neither III nor IV grades were obtained. Pre-surgical studies changed in comparison with the previous report. The most improving change was observed in video-EEG with foramen-ovale electrodes (FOE) (37%), scalp EEG (26.6%), interictal SPECT (11.7%) and MRI (11.7%). Video-EEG with FOE was the study than showed greater concordance with epileptic focus (95.5%), followed by EEG (86.4%). In 35% of cases, MRI was normal or without valid data for correct localization of focus. CONCLUSIONS: Video-EEG with FOE and TLE surgery are safety methods, which results improve with the experience. Normal or not informative MRI do not should a priori reject those patients with drug-resistant TLE from surgery.

Adolescent↗

PubMed2004

Diagnosis and treatment of temporal lobe epilepsy.

Of the 1,200,000 Americans with partial epilepsy, temporal lobe epilepsy (TLE) occurs in more than 400,000. Temporal lobe seizures are usually stereotypic in their symptoms and duration. A typical sequence is an aura followed by arrest of motor behavior, blank stare, and automatisms. Patients with TLE often show impairments in attention, memory, mental processing speed, executive functions, mood, personality, and drive-related behaviors. Interictal depression occurs in approximately one third of TLE patients. TLE is diagnosed by a history of characteristic partial seizure symptoms. The diagnosis is confirmed by the capture of a typical episode during an electroencephalogram (EEG) or video-EEG, with epileptiform activity over one or both temporal regions. Video-EEG monitoring has revolutionized diagnosis and should be considered in patients in whom diagnosis is uncertain. TLE is treated with medications, resective surgery, and vagus nerve stimulation. Epilepsy surgery should be considered in all patients with refractory partial epilepsy.

Epilepsy, Temporal Lobe↗

PubMed2006

Degree of hippocampal atrophy is related to side of seizure onset in temporal lobe epilepsy.

BACKGROUND AND PURPOSE: Temporal lobe epilepsy (TLE) is associated with pathologic changes in hippocampal physiology and morphology. Our aim was to quantify volume reduction of the right and left hippocampus in patients with TLE and to investigate whether the degree of hippocampal atrophy is related to the side of seizure onset. METHODS: The volume of the right and left hippocampus was estimated for 50 controls and 101 patients with TLE, by applying the unbiased Cavalieri method on MR images. RESULTS: Pairwise comparisons, within a multivariate analysis of variance and adjusted by using the Bonferroni correction, revealed that both right and left hippocampal volumes were, on average, significantly smaller in patients with right-sided seizure onset (R-patients) relative to those of controls (P < .001 and P = .04, respectively). Furthermore, left hippocampal volume was significantly smaller in patients with left-sided seizure onset (L-patients) compared with controls (P < .001), but the right-sided hippocampal volume was not significantly smaller (P = .71). Moreover, a correlation analysis revealed that the strong linear association between the right and left hippocampal volumes existing in the control population (r = 0.73) is partially lost in patients with TLE (r < or = 0.48), and this loss in correlation appears to be more pronounced in L-patients than in R-patients. CONCLUSION: Our MR imaging results suggest that although the major damage in patients with TLE is located in the hippocampus ipsilateral to the side of seizure onset, R-patients are more likely to have bilateral hippocampal volume reduction. These findings support the hypothesis that cerebral hemispheres may not only differ in their functionality organization but also in their vulnerability to a neurologic insult.

Adult↗

PubMed1981

Affinity chromatography of Streptomyces erythreus trypsin-like enzyme on Japanese quail ovomucoid.

For simple, rapid purification of Streptomyces erythreus trypsin-like enzyme (TLE), we examined affinity chromatography with quail ovomucoid (QO) as a ligand of an affinity matrix. We prepared two affinity matrices by the cyanogen bromide method and the oxirane coupling method, and compared their binding efficiencies for TLE using frontal affinity chromatography. The affinity matrix in which QO was immobilized by the cyanogen bromide method showed 30% binding efficiency. However, another matrix, in which QO was immobilized by the oxirane coupling method with the lysine residue of the reactive site blocked by citraconylation, showed 92% binding efficiency. The results suggest that some biologically inactive QO was formed during the coupling reaction by the cyanogen bromide method. When we purified TLE from S. erythreus culture broth by affinity chromatography on QO-Sepharose, TLE was purified about 1,100-fold by affinity chromatography, and was further purified by DEAE-Sephadex A-25 column chromatography to homogeneity. The overall yield of TLE activity was higher than 90%. Thus, we were able to greatly improve previous purification procedures.

Animals↗

PubMed1993

[MRI hippocampal volumetric measurements in benign childhood epilepsy with centrotemporal spike(s) and temporal lobe epilepsy of childhood onset].

Benign childhood epilepsy with centrotemporal spike(s) (BCECT) is characterized by rolandic discharges (RD) on EEG. As the origin of RD, the lower rolandic cortex was proposed by Lombroso, but recently the hippocampus was proposed by some reports, based on the character of RD or the pharmacological effects of anticonvulsants. On the other hand, MRI hippocampal volumetric measurements revealed the relationship between the hippocampal atrophy and EEG foci in intractable temporal lobe epilepsy (TLE) of adults, but there are a few reports of the hippocampal volumetric study in children. Therefore, in this paper, we reported about MRI hippocampal volumetric measurements in BCECT and TLE of childhood onset. The statistical examination was performed by t-test. MRI hippocampal volumetric measurements were performed in 27 cases with BCECT (6-19 years, 9.9 +/- 2.7 years, 11 males, 16 females), 22 cases with TLE (5-22 years, 12.9 +/- 5.5 years, 15 males, 7 females) and 17 normal control subjects (6-15 years, 10.4 +/- 2.7 years, 10 males, 7 females). The age was not significantly different among the 3 groups. The clinical course of TLE group was significantly longer than BCECT group, but the onset age of epilepsy was not significantly different between the 2 groups. The hippocampal volume and the right-side minus left-side volume were not significantly different in 3 groups, but these values of TLE were more scattered than the others. There was no abnormal signal intensity in hippocampus on MRI, or no specific abnormality in the surrounding structures in 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1996

Quantification of serial tumor glucose metabolism.

UNLABELLED: We developed a method to improve the quantitative precision of FDG-PET scans in cancer patients. The total-lesion evaluation method generates a correlation coefficient (r) constrained Patlak parametric image of the lesion together with three calculated glucose metabolic indices: (a) the total-lesion metabolic index ("KT-tle", ml/min/lesion); (b) the total-lesion voxel index ("VT-tle", voxels/lesion); and (c) the global average metabolic index ("KV-tle", ml/min/voxel). METHODS: The glucose metabolic indices obtained from conventional region of interest (ROI) and multiplane evaluation were used as standards to evaluate the accuracy of the total-lesion evaluation method. Computer simulations and four patients with metastatic melanoma before and after chemotherapy were studied. RESULTS: Computer simulations showed that the total-lesion evaluation method has improved precision (% s.d. < 0.6%) and accuracy (approximately 10% error) compared with the conventional ROI method (% s.d. approximately 5%; approximately 25% error). The KT-tle and VT-tle indices from human FDG-PET studies using the total-lesion evaluation method showed excellent correlations with the corresponding values obtained from the conventional ROI methods and multiplane evaluation (r approximately 1.0) and CT lesion volume measurements. CONCLUSION: This method is a simple but reliable way to quantitatively monitor tumor FDG uptake. The method has several advantages over the conventional ROI method: (a) less sensitive to the ROI definition, (b) no need for image registration of serial scan data and (c) includes tumor volume changes in the global tumor metabolism.

Computer Simulation↗

PubMed1997

Hippocampal loss of tenascin boundaries in Ammon's horn sclerosis.

Ammon's horn sclerosis (AHS) is a common finding in patients with temporal lobe epilepsy (TLE). In addition to selective neuronal cell loss and axonal reorganization, AHS is also characterized by a striking astroglial reaction. However, the functional significance of reactive astrogliosis in the pathogenesis of TLE remains to be determined. Reactive astrocytes produce a variety of cell adhesion molecules and other extracellular matrix (ECM) components with potential effects on axonal growth, axonal branching, and neosynaptogenesis in the central nervous system (CNS). In the present study we describe the distribution of the ECM glycoprotein tenascin/cytotactin (TN-C) in 44 human hippocampal specimens from patients with TLE. The distribution of TN-C immunoreactivity was evaluated with the anti-human TN-C monoclonal antibody K8 by densitometrical analysis, and TN-C protein levels were detected by immunoblotting. In the normal human hippocampus, there were distinctive boundaries between areas of high and low TN-C expression. These border zones demarcated areas with major synaptic input, i.e., the dentate gyrus molecular layer (DG-ML) and the gray matter of the Ammon's horn. TN-C and the neurite growth-associated protein GAP-43 exhibited a complementary pattern of distribution. Densitometric and protein biochemical analysis showed a significant, 4.3-fold increase of TN-C in the hippocampus of TLE patients with AHS compared with normal hippocampus obtained at autopsy. This increase in TN-C immunoreactivity was accompanied by a loss of TN-C boundaries and closely correlated with the extent of reactive gliosis, as indicated by immunoreactivity for glial fibrillary acidic protein. Furthermore, a striking colocalization between TN-C and GAP-43 was observed in the DG-ML of patients with AHS. These observations raise the intriguing possibility of pathogenetically relevant glio-neuronal interactions in human TLE.

Antibody Specificity↗

PubMed1997

[Glutamatergic excitatory receptors and temporal lobe epilepsy].

Despite a considerable wealth of data, the mechanisms responsible for the generation of epileptic bursts in temporal lobe epilepsy (TLE) remain a mystery. Recently, research and therapy have focused on impairment of GABAergic inhibition in epilepsy. Several lines of evidence support this approach: 1-GABA is the main inhibitory neurotransmitter in the neuronal structures involved in TLE. 2-Enhancers of GABAergic inhibition (such as benzodiazepines or barbiturates) are commonly used as antiepileptic drugs. 3-Interictal discharges can be obtained following the pharmacological blockade of GABAA receptors. Since the axiom at the basis of epilepsy research states that the balance between inhibition and excitation is tipped toward excitation, we have addressed the following question: where are the loci most likely to be involved in such imbalance? We have limited our investigation to the excitatory side of the story. The main glutamatergic excitatory receptors (AMPA and NMDA) involved in TLE and their properties will be first addressed. We will focus on the excitatory synapses most likely involved in epileptogenesis. We have then specifically studied the effects of redox reagents on NMDA receptor-dependent epileptiform activity in a chronic animal model of TLE, the kainic acid lesioned rat hippocampus. We report that oxidizing drugs abolish evoked epileptiform discharges via a decrease by 50 p. 100 of NMDA receptor-mediated responses without affecting synaptic plasticity and thus memory and learning. The dormant cell hypothesis (i.e. the disconnection of inhibitory interneurons from their excitatory afferents) was also tested. We report that interneurons are not dormant in TLE and fire bursts of action potentials during spontaneous or evoked paroxismal activity.

Animals↗

PubMed2000

Is ictal recording mandatory in temporal lobe epilepsy? Not when the interictal electroencephalogram and hippocampal atrophy coincide.

OBJECTIVE: To investigate the concordance between scalp electroencephalogram (EEG) lateralization and side of hippocampal atrophy in patients with temporal lobe epilepsy (TLE). METHODS: We studied 184 consecutive patients with TLE without lesions other than those compatible with mesial temporal sclerosis. In this study, we studied specifically hippocampal atrophy and the results of scalp EEG investigation. Patients were classified according to the localization of interictal epileptiform discharges as unilateral, bilateral asymmetric, and bilateral symmetric. The EEG seizure onsets were also classified separately as unilateral, bilateral asymmetric, and bilateral symmetric. The hippocampal atrophy was determined by volumetric measurements using high-resolution magnetic resonance imaging (MRIVol). RESULTS: Only 3% of patients had discordance between the ictal and interictal EEG lateralizations; however, none of these had unilateral interictal EEG abnormalities. Interictal EEGs were considered unilateral in 62.0% of patients, bilateral asymmetric in 31.5%, and bilateral symmetric in 6.5%. Ictal EEGs were considered unilateral in 63.5% of patients, bilateral asymmetric in 30.0%, and bilateral symmetric in 6.5%. The MRIVol showed unilateral hippocampal atrophy in 60.9% of patients, bilateral asymmetric hippocampal atrophy in 19.0%, symmetric hippocampal atrophy in 3.8%, and normal volumes in 16.3%. There was a significant concordance between MRIVol lateralization and both interictal and ictal EEG lateralization (P<.001). All patients with unilateral hippocampal atrophy had concordant interictal and ictal EEG lateralization. Six (18.2%) of the 33 patients with bilateral asymmetric hippocampal atrophy had MRI lateralization discordant with EEG lateralization. CONCLUSIONS: We found a strong concordance between EEG and MRIVol lateralization in patients with TLE. Unilateral hippocampal atrophy predicted ipsilateral interictal epileptiform abnormalities and ipsilateral seizure onsets with no false lateralization. Previous studies in addition to the present series support that a concordant outpatient EEG evaluation in patients with TLE and unilateral hippocampal atrophy would obviate the need for inpatient EEG monitoring.

Adult↗

PubMed2005

Bilateral limbic diffusion abnormalities in unilateral temporal lobe epilepsy.

Diffusion tensor magnetic resonance imaging can acquire quantitative information on the microstructural integrity of white matter structures and depict brain connectivity in vivo based on the behavior of water diffusion. Diffusion tensor imaging-derived tractography has been used for virtual dissection of the fornix and cingulum in healthy subjects, but not in patients with temporal lobe epilepsy (TLE). Eight patients with medically intractable TLE and unilateral mesial temporal sclerosis and nine healthy control subjects were imaged using diffusion tensor imaging. Fiber tracking was performed to delineate the fornix and cingulum, which were quantitatively analyzed. Bilateral symmetrical reduction in fractional anisotropy was observed in the fornix of patients with TLE, together with an increase in water mobility perpendicular to the axis of the fibers. The findings in the cingulum are similar to those of the fornix with the exception of significantly increased bulk diffusivity in the latter. We observed strikingly symmetrical bilateral abnormalities of axonal integrity in the fornix and cingulum in a series of patients with unilateral mesial temporal sclerosis. Our findings suggest that TLE with unilateral mesial temporal sclerosis is associated with bilateral limbic system pathology.

Adult↗

PubMed2001

Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy.

A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin-immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE.

Adolescent↗

PubMed2006

Hippocampal neurodegeneration, spontaneous seizures, and mossy fiber sprouting in the F344 rat model of temporal lobe epilepsy.

The links among the extent of hippocampal neurodegeneration, the frequency of spontaneous recurrent motor seizures (SRMS), and the degree of aberrant mossy fiber sprouting (MFS) in temporal lobe epilepsy (TLE) are a subject of contention because of variable findings in different animal models and human studies. To understand these issues further, we quantified these parameters at 3-5 months after graded injections of low doses of kainic acid (KA) in adult F344 rats. KA was administered every 1 hr for 4 hr, for a cumulative dose of 10.5 mg/kg bw, to induce continuous stages III-V motor seizures for >3 hr. At 4 days post-KA, the majority of rats (77%) exhibited moderate bilateral neurodegeneration in different regions of the hippocampus; however, 23% of rats exhibited massive neurodegeneration in all hippocampal regions. All KA-treated rats displayed robust SRMS at 3 months post-KA, and the severity of SRMS increased over time. Analyses of surviving neurons at 5 months post-KA revealed two subgroups of rats, one with moderate hippocampal injury (HI; 55% of rats) and another with widespread HI (45%). Rats with widespread HI exhibited greater loss of CA3 pyramidal neurons and robust aberrant MFS than rats with moderate HI. However, the frequency of SRMS (approximately 3/hr) was comparable between rats with moderate and widespread HI. Thus, in comparison with TLE model using Sprague-Dawley rats (Hellier et al. [1998] Epilepsy Res. 31:73-84), a much lower cumulative dose of KA leads to robust chronic epilepsy in F344 rats. Furthermore, the occurrence of SRMS in this model is always associated with considerable bilateral hippocampal neurodegeneration and aberrant MFS. However, more extensive hippocampal CA3 cell loss and aberrant MFS do not appear to increase the frequency of SRMS. Because most of the features are consistent with mesial TLE in humans, the F344 model appears ideal for testing the efficacy of potential treatment strategies for mesial TLE.

Animals↗

PubMed1997

Temporal lobe epilepsy: correlation of proton magnetic resonance spectroscopy and 18F-fluorodeoxyglucose positron emission tomography.

Proton magnetic resonance spectroscopy (MRS) has demonstrated reduction of N-acetylaspartate (NAA) in the epileptogenic temporal lobe. However, the correlation of NAA reduction with cerebral metabolic abnormalities is unknown in temporal lobe epilepsy (TLE). Proton MRS and 18F-fluorodeoxyglucose positron emission tomography (FDG/PET) were used to study 12 unilateral TLE patients with medically intractable seizures and 26 age-matched healthy volunteers. The epileptogenic temporal lobe of each patient was determined by both electroencephalography and FDG/PET. The NAA/choline-plus-creatine (NAA/(Cho+Cr)) ratio correlated significantly with the interictal glucose metabolism (r = 0.54, P < 0.01) in 12 TLE patients. The mean NAA/(Cho+Cr) ratio in the epileptogenic temporal lobe was significantly less than that in the contralateral side (P < 0.01), and less than that in normal control temporal lobes (P < 0.0001). These results suggest that quantitative MRS abnormalities reflect underlying metabolic pathology in TLE.

Adult↗