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PubMed1987

Hyperreligiosity in temporal lobe epilepsy: redefining the relationship.

Seventy-six subjects with the primary diagnosis of complex partial seizures with a unilateral temporal lobe focus were examined for the presence of hyperreligiosity. Fifty-one subjects had a left temporal lobe seizure focus and 25 had a right temporal lobe seizure focus. In addition to the temporal lobe epilepsy (TLE) groups, two reference groups were also examined. The first consisted of 31 subjects with primary generalized seizures. The second control group consisted of 27 subjects with documented pseudoseizures and no objective evidence of recurrent epileptic seizures. In all cases, the documentation of seizures or pseudoseizures as well as the localization of the seizure focus was accomplished through simultaneous videotaped recording of the 16-channel scalp EEG tracing and the concurrent overt behavior during the ictal phase. The results of this study fail to support the hypothesis that individuals with TLE are characteristically hyperreligious during the interictal state. There were no significant group differences between the left vs. the right TLE groups, nor were there any significant group differences between the two TLE groups vs. the two comparison groups.

Brain↗

PubMed1996

[Magnetic resonance imaging of temporal lobe epilepsy].

MR has gained more and more importance in the evaluation of patients with temporal lobe epilepsy (TLE). Until recently, hippocampal sclerosis (which is the most frequent cause of temporal lobe epilepsy, accounting for 50-70% of the cases) could not be identified reliably. Using optimized magnetic resonance imaging techniques, hippocampal sclerosis can now be evidenced in a large proportion of patients with TLE. Tumors (10-15%), developmental abnormalities (5-7%), vascular malformations (mostly cavernous angiomas, 1-5%), and traumatic scars (5-10%) represent the other structural lesions associated with TLE. Studies of large series of patients with intractable epilepsy or with varying severity have shown that in only 8.5% and 20%, respectively, a specific imaging abnormality was not found. Specific MR sequences increase the diagnostic value of MR (coronal images perpendicular to the axis of the hippocampal formations, three-dimensional T1 weighted images, inversion recovery images, volumetry or more specific processes such as T1 and T2 relaxometry or spectroscopy). MR also helps guide placement of intra-cerebral and subdural electrodes in surgically relevant cases. All these results have given greater importance to MR in the definition of the epileptic syndrome of TLE and should probably be integrated in the criteria of international classifications.

Adult↗

PubMed2026

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE↗

PubMed1984

Behavioral disorders in multiple sclerosis, temporal lobe epilepsy, and amyotrophic lateral sclerosis. An epidemiologic study.

Certain CNS diseases can produce specific behavioral abnormalities. We used a computer search technique to identify all inpatients at Strong Memorial Hospital, Rochester, NY, who had received diagnoses of multiple sclerosis (MS), temporal lobe epilepsy (TLE), and amyotrophic lateral sclerosis (ALS) between 1965 and 1978. We found 368 patients with MS, 402 patients with TLE, and 124 patients with ALS. These groups were matched against the Monroe County (New York) Psychiatric Register to determine patterns of behavioral pathology. Prevalence rates for psychiatric contact were not significantly different between MS and TLE (19.3% v 22.9%), but both were higher than the prevalence rate for ALS (4.8%). When behavioral patterns were assessed, patients with MS demonstrated a significantly higher rate of depressed affective disorders (61.97% of register matches) than patients with the other two diseases. Multiple sclerosis may present a neurologic model for mood disturbance.

Amyotrophic Lateral Sclerosis↗

PubMed1986

Reproductive endocrine disorders in women with partial seizures of temporal lobe origin.

Of 50 consecutive women with partial seizures of temporal lobe origin (temporal lobe epilepsy [TLE]) evaluated for reproductive dysfunction, 28 had menstrual problems. Of those, 19 had reproductive endocrine disorders. Polycystic ovarian syndrome and hypogonadotropic hypogonadism occurred significantly more often in women with TLE than in the general female population. Polycystic ovarian syndrome was associated with predominantly left-sided lateralization of interictal epileptic discharges; hypogonadotropic hypogonadism was more commonly found with right-sided discharges. Hyposexuality occurred more often in women with predominantly right-sided interictal epileptic discharges and was associated with low serum luteinizing hormone levels. There are several possible interpretations: epileptic discharges in medial temporal limbic structures may disrupt hypothalamic regulation of pituitary gonadotropin secretion; anovulatory cycles of reproductive endocrine disorders may promote the development of epileptic discharges; and TLE and some associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of the brain and the reproductive system.

Adult↗

PubMed2000

Postoperative changes in cerebral metabolism in temporal lobe epilepsy.

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452

Adult↗

PubMed2000

The Memory Assessment Scales and lateralized temporal lobe epilepsy.

We report Memory Assessment Scales (MAS) performance in 101 patients with unilateral temporal lobe epilepsy (TLE; left, n = 51; right, n = 50) with left cerebral language dominance. A significant multivariate group effect was present for the major summary indices (Verbal Memory, Visual Memory, and Global Memory, p < .04). Univariate analyses revealed no significant differences for either the Global Memory or Verbal Memory summary scores, although a significant group difference was present for Visual Memory (p < .04). The Verbal Memory-Visual Memory discrepancy score was significantly different between right and left TLE groups (p < .004). Verbal Memory scores were at least 14 points lower than Visual Memory scores in 34 patients (left = 20, 59%; right = 14, 41%). Visual Memory scores were at least 14 points lower than Verbal Memory performance in 20 patients (left = 5, 25%; right = 15, 75%). Diagnostic efficiency statistics show higher sensitivity but lower specificity in group classification for left TLE patients. These data suggest that the MAS is sensitive to material-specific memory deficits associated with a unilateral temporal lobe seizure focus. However, over one-third of the patients (19/54) with at least a 14-point Verbal Memory-Visual Memory discrepancy were classified incorrectly. The MAS, like other material-specific memory measures, should be interpreted within the context of other clinical findings.

Adult↗

PubMed2005

Cystatin C expression is associated with granule cell dispersion in epilepsy.

Human temporal lobe epilepsy (TLE) is associated with cellular alterations (eg, hilar cell death, neurogenesis, and granule cell dispersion) in the dentate gyrus but their underlying molecular mechanism are not known. We previously demonstrated increased expression of cystatin C, a protease inhibitor linked to both neurodegeneration and neurogenesis, during epileptogenesis in the rat hippocampus. Here, we investigated cystatin C expression in the dentate gyrus in chronic epilepsy and its association with neuronal loss and neurogenesis. In both rats with epilepsy and human patients with TLE, cystatin C expression was increased in glial cells in the molecular layer of the dentate gyrus, being most prominent in cases with granule cell dispersion. In patients with TLE, high cystatin C expression associated with greater numbers of polysialylated neural cell adhesion molecule-positive newborn cells in the molecular layer, although the overall number was decreased, indicating that the newborn cells migrate to abnormal locations in the epileptic dentate gyrus. These data thus demonstrate that cystatin C expression is altered during the chronic phase of epilepsy and suggest that cystatin C plays a role in network reorganization in the epileptic dentate gyrus, especially in granule cell dispersion and guidance of migrating newborn granule cells.

Adolescent↗

PubMed1997

Increased apolipoprotein E epsilon 4 in epilepsy with senile plaques.

Inheritance of the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and is associated with increased deposition of beta-amyloid (A beta) in AD, Down's syndrome, and normal aging. A beta deposition in the form of senile plaques (SPs) has recently been described in patients with temporal lobe epilepsy (TLE). We studied the relationship between ApoE epsilon 4 genotype and the deposition of A beta in temporal lobe tissue from patients who underwent temporal lobectomy for intractable epilepsy. TLE patients with SPs had a 70% ApoE epsilon 4 carrier frequency compared with a 27% carrier frequency among age-matched TLE controls without SPs. Our data suggest that the association between ApoE epsilon 4 and intracerebral A beta accumulation is not unique to the elderly or to those with dementia, and may be a feature of conditions in which there is both an ApoE epsilon 4 allele and over-production of A beta precursor protein, and, presumably, A beta.

Amyloid beta-Peptides↗

PubMed1997

Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: a series of 100 patients.

Surgery is a safe and effective treatment for drug-resistant temporal lobe epilepsy (TLE). However, bilateral electroencephalographic (EEG) abnormalities are frequently present, making presurgical lateralization difficult. New magnetic resonance (MR) techniques can help; proton magnetic resonance spectroscopic imaging (MRSI) can detect and quantify focal neuronal damage or dysfunction based on reduced signals from the neuronal marker N-acetylaspartate, and magnetic resonance imaging (MRI)-based measurements of amygdala-hippocampal volumes (MRIVol) can improve the detection of atrophy of these structures. We performed proton MRSI and MRIVol in 100 consecutive patients with medically intractable TLE to determine how well these techniques agreed with the lateralization by extensive EEG investigation. We found that the EEG, MRSI, and MRIVol findings were highly concordant. The MRSI was abnormal in 99 of 100 patients (bilateral in 54%). The MRIVol was abnormal in 86 of 98 patients (bilateral in 28%). We obtained lateralization in 83% of patients using MRIVol alone, in 86% using MRSI alone, and in 90% by combining MRSI and MRIVol (vs 93% lateralization by EEG). MRSI was abnormal in 12 patients with normal MRIVol. The combination of proton MRSI and MRIVol can lateralize TLE accurately and noninvasively in the great majority of patients. By reducing reliance on EEG, these imaging techniques could reduce prolonged presurgical evaluation and make seizure surgery available to more patients.

Adult↗

PubMed2004

Impaired associative memory in temporal lobe epilepsy subjects after lesions of hippocampus, parahippocampal gyrus, and amygdala.

There has been growing interest in the differential role of medial temporal lobe structures in learning and memory. The goal of the present study was to clarify how lesions of hippocampus, parahippocampal gyrus, and amygdala interfere with associative learning and memory. Thirty subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 30 matched healthy control subjects. A set of neuropsychological test measures and an associative learning task requiring the learning and recall of objects and faces were administered. The lesions of hippocampus, parahippocampal gyrus, amygdala, and fusiform gyrus of TLE subjects were determined by three-dimensional magnetic resonance imaging (3-D MRI) volumetric assessment. The results indicate that TLE subjects with combined large hippocampal lesions, large parahippocampal gyrus (i.e., perirhinal/entorhinal) lesions, and large amygdala lesions learned and recalled the associative task significantly worse than control subjects or subjects with small lesions of the hippocampus, parahippocampal gyrus, and amygdala. Regression analysis revealed that larger lesions of the parahippocampal gyrus (i.e., perirhinal/entorhinal cortices) were significantly related to increasing deficits on the task, and that hippocampal and amygdala lesion size did not significantly improve the prediction. Our results suggest that perirhinal and entorhinal cortices may contribute predominantly to the associative learning and recall of objects and faces.

Adult↗

PubMed2007

Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model.

In the study of temporal lobe epilepsy (TLE) the characterization of genes expressed in the hippocampus is of central importance for understanding their roles in epileptogenic mechanisms. Although several large-scale studies on TLE gene expression have been reported, precise assignment of individual genes associated with this syndrome is still debatable. Here we investigated differentially expressed genes by comparison of mRNAs from normal and epileptic rat hippocampus in the pilocarpine model of epilepsy. For this we used a powerful EST sequencing methodology, ORESTES (Open Reading frame Expressed Sequence Tags), which generates sequence datasets enriched for mRNAs open reading frames (ORFs) rather than simple 5' and 3' ends of mRNAs. Analysis of our sequences shows that ORESTES readily enables the identification of epilepsy associated ORFs. PFAM analysis of protein motifs present in our ORESTES epilepsy database revealed diverse important protein family domains, such as cytoskeletal, cell signaling and protein kinase domains, which could be involved in processes underlying epileptogenesis. More importantly, we show that the expression of homer 1a, known to be coupled to mGluR and NMDA synaptic transmission, is associated with pilocarpine induced status epilepticus (SE). The combined use of the pilocarpine model of epilepsy with the ORESTES technique can significantly contribute to the identification of specific genes and proteins related to TLE. This is the first study applying a large-scale method for rapid shotgun sequencing directed to ORFs in epilepsy research.

Animals↗

PubMed2001

A fast FLAIR dual-echo technique for hippocampal T2 relaxometry: first experiences in patients with temporal lobe epilepsy.

To evaluate the use of cerebrospinal fluid (CSF) signal nulling in MR T2 measurements of the hippocampus in normal control subjects and patients with temporal lobe epilepsy (TLE), dual-echo acquisitions covering the whole brain were used. T2 relaxation times were estimated in 12 standard Eurospin II MR test objects and in the hippocampi of 10 control subjects, using T2 maps constructed from conventional spin-echo (CSE), fast spin-echo (FSE), and fast FLAIR (FF) dual-echo sequences on a 1.5-T MR scanner. Hippocampal T2 values (HCT2) were measured on contiguous coronal 5-mm slices throughout the antero-posterior extent of each hippocampus in the 10 controls and 12 TLE patients, using both CSE and FF. Scan-rescan reproducibility in Eurospin II standard MR test objects was high for all sequences. There was a good correlation between T2 values from CSE, FF, and FSE sequences in test objects and in control hippocampi. In controls, the coefficient of variation of mean HCT2 values differed between slice positions, but was lowest for FF, followed by CSE data. The intrarater coefficient of reliability between repeated measurements in control subjects was lowest for FF HCT2, at 2.3%. The interrater coefficient of reliability for CSE HCT2 measurements in controls (4.8%) was slightly lower than the interrater coefficient for FF HCT2 (5.4%). HCT2 measurement with both CSE and FF identified abnormal values in the same 10 hippocampi of 12 patients. Hippocampal dual-echo T2 relaxometry using CSF nulling is reliable in control subjects, and identifies the abnormal hippocampi in patients with TLE. The increases in hippocampal T2 signal demonstrated using FF HCT2 measurements are unlikely to be partial volume effects from CSF.

Adult↗

PubMed1992

Preparation of a protein-free total brain white matter lipid fraction: characterization of liposomes.

A method of preparing a total lipid extract (TLE), free of protein, by extracting brain white matter with tetrahydrofuran is presented. The optimal conditions of extraction were found to be 50 ml of THF per gram of lyophilized tissue, though fresh tissue can also be used if larger volumes of solvent are employed. The method allowed, in a short time and in a single step, a yield of TLE of 50% on a dry weight basis. Its analytical characterization revealed a qualitative and quantitative composition very similar to the lipid composition of CNS myelin, including all the phospholipid and galactolipid species, cholesterol and gangliosides, but it contained only traces (0.1%) of protein. TLE has been used to prepare liposomes, either multilamellar (MLVs) or unilamellar (LUVs, SUVs), characterized by freeze-fracture electron microscopy. A multilayered, heterogeneous population of liposomes is observed in the MLVs preparation. When these samples were submitted to a freezing and thawing procedure the resulting liposomes were single-walled, and their intravesicular volume was increased. They were quite impermeable to the monovalent cation 86Rb+ and, by contrast, rather permeable to 45Ca+ +. Their complex lipid composition, together with their permeability properties and their response to ionophores, make them very useful to study protein-lipid interactions occurring within the myelin membrane as well as the functional properties of myelin proteins in reconstitution experiments.

Animals↗

PubMed2006

Proteomic analysis and comparison of the biopsy and autopsy specimen of human brain temporal lobe.

The proteomic study on human temporal lobe can help us to understand the physiological function of CNS in normal as well as in pathological state. Proteomic tools are potent for the assessment of protein stability post mortem. In this pilot study, the human temporal lobe biopsy specimen with chronic pharmacoresistant temporal lobe epilepsy (TLE) and autopsy specimen in control were separated by 2-DE. Using MALDI-TOF-MS and MS/MS, 375 protein spots were identified which were the products of 267 genes. Six down-regulated and 23 up-regulated protein spots in the autopsy specimen were ascertained after the gel image analysis with the ImageMaster software. A number of proteins that include neurotransmitter metabolic and glycolytic enzymes, cytoprotective proteins and cytoskeleton were found decreased while the precursor of apolipoprotein A-I increased in the TLE brain. We tried several methods to prepare the protein samples and found that DNase and RNase treatment, ultracentrifugation and Amersham clean-up kit purification can improve gel separation quality. This work optimized the sample preparation method and constructed a primary protein database of human temporal lobe and found some proteins with remarkable level change probably involved in the post-mortem process and chronic pharmacoresistant TLE pathogenesis.

Autopsy↗

PubMed1997

The role of the temporal lobes in recognizing visuospatial materials: remembering versus knowing.

Recognition memory for abstract visuospatial designs was assessed in unilateral temporal lobe epilepsy (TLE) patients and normal controls using a remember/know recognition paradigm. Subjects assigned "remember" judgments to recognized items for which they could recall the study presentation, and "know" judgments to items recognized on the basis of familiarity without conscious recollection of the study episode. In Experiment 1 normal controls and left TLE patients gave more "know" than "remember" recognition judgments for visuospatial materials. Right TLE subjects, however, showed the opposite response pattern. Experiment 1a demonstrated that this dissociation between left and right temporal patients occurred in both presurgery and postsurgery patients. In Experiment 2 recognition was assessed following encoding conditions in which subjects answered questions about either the number of lines in the designs or the appropriateness of verbal labels for presented stimuli. The previous pattern of "know" and "remember" responses was replicated for all groups in the line count condition, but was reversed for normal controls in the label condition. These results are interpreted within a theoretical framework in which "remember" responses are based on the contribution of distinctiveness of individual items to recognition whereas "know" judgements reflect perceptual fluency.

Adult↗

PubMed2000

The Frontal Lobes, Epilepsy, and Behavior.

The frontal lobes have been overshadowed by the temporal lobes in the vast literature addressing the neurobehavioral and psychological perspectives of epilepsy. The purpose of this review is to summarize contemporary anatomicobehavioral correlations and to highlight the frontal lobe contributions to the neurology, neuropsychology, and neuropsychiatry of epilepsy, in general, and to temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE), in particular. Much evidence has accumulated suggesting that focal epileptogenic tissue may have effects on distant neural systems. Data supporting the case that the frontal regions are preferentially affected in TLE are presented. Emphasis is placed on the results of numerous functional imaging studies demonstrating correlations between frontal hypoperfusion and cognitive or mood impairments in patients with TLE.

Journal Article↗

PubMed2001

Depression and Anxiety in Patients with Epilepsy.

The aim of this investigation was to study the interaction between depression/anxiety and epilepsy. One hundred fifty individuals with partial epilepsy, 70 with idiopathic generalized epilepsy, and 100 controls were administered two self-rating mood questionnaires (Zung and Stai) for the evaluation of depression and anxiety, respectively. The group with epilepsy was much more severely impaired than the controls according to both mood questionnaires; the patients with partial epilepsy, especially those with temporal lobe epilepsy (TLE), were more depressed and anxious than the patients with generalized epilepsy. The group with left TLE appeared to have the highest levels of depression and anxiety. The final results of our study confirmed that some mood disorders are common throughout the epilepsy population, especially in patients with left TLE. No correlation was noted between the frequency of seizures and onset of epilepsy and the results of the mood questionnaires. Moreover, no differences were found in depression and anxiety between males and females among both left focus and right focus epilepsy patients.

Journal Article↗