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PubMed2001

Prevalence of Psychopathology in Dutch Epilepsy Inpatients: A Comparative Study.

The purpose of this study was to determine the prevalence of psychiatric disorders in Dutch patients with epilepsy in comparison with epidemiological data on a representative sample of the Dutch population. The Composite International Diagnostic Interview (CIDI) was used to determine the prevalence of psychiatric disorders in 209 epilepsy patients and compared with findings in the general Dutch population. The prevalence in temporal lobe epilepsy (TLE) and extra-temporal lobe epilepsy (extra-TLE) was also compared. Psychiatric disorders most frequently found in patients with epilepsy were anxiety and mood disorders. The last-year prevalence of these disorders was 25% for anxiety disorders and 19% for mood disorders. Compared with the general Dutch population, the prevalence of these disorders was significantly higher in epilepsy. No differences were found between patients with TLE and extra-TLE. It can be concluded that patients with epilepsy admitted to a tertiary epilepsy center suffer more often from mood and anxiety disorders than the general population.

Journal Article↗

PubMed1998

Neuronal cyclin expression in the hippocampus in temporal lobe epilepsy.

This study used immunocytochemistry to explore the expression of cyclins A, B, D, and E and the apoptosis-associated Bax protein in hippocampal subfields of 35 lobectomy specimens with medial temporal lobe sclerosis removed for the treatment of temporal lobe epilepsy (TLE), 2 age-matched controls, and 2 elderly patients suffering from drug-responsive epilepsy. Cyclins A and D were not detected at all in neuronal nuclei. Cyclin E was only rarely detected in neuronal nuclei in drug-controlled and TLE groups and in controls. Cyclin B was expressed in significantly more neuronal nuclei in the hippocampi in TLE than in the other groups studied. The nuclear expression of these proteins suggested that neurons had reentered the cell division cycle and reached the G2 phase. The nuclear expression of cyclin B in the hippocampus from these patients was accompanied by neuronal cytoplasmic expression of the death-related Bax protein. We interpret these neuronal findings as evidence of cell cycle disturbances and a possible apoptotic mechanism of hippocampal neuronal cell death in TLE.

Adult↗

PubMed2004

Preoperative clinical evaluation, outline of surgical technique and outcome in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy. The mechanisms of epileptogenesis and seizure semiology of the mesial and neocortical temporal lobe epilepsy are discussed. The evaluation and selection of patients for TLE surgery requires team work: the different clinical aspects of neuropsychological evaluation, magnetic resonance and functional imaging (positron emission tomography, single photon emission computed tomography and magnetoenephalography) are reviewed. In our programme of epilepsy surgery at Kuopio University Hospital, Finland, we have performed 230 temporal resections from 1988 until 2002. Preoperative diagnostic EEG-videotelemetry often required intracranial monitoring and it has proved to be safe and efficient. The indications and technique for tailored temporal lobe resection with amygdalohippocampectomy used in our institution, as well as the complications, are described. Our analysis of outcome after temporal lobe surgery included 140 consecutive adult patients between 1988 and 1999; one year after the operation in unilateral TLE the Engel I-II outcome was observed in 68% of the patients. Outcome of surgery improved significantly after introduction of the standardised MR imaging protocol from 1993; 74% of patients with unilateral TLE achieved Engel I-II outcome.

Electroencephalography↗

PubMed1978

Substance P: binding to lipids in the brain.

1. Substance P (SP) could be extracted from brain homogenates with chloroform-methanol by a method which extracts all lipids. 2. SP could be transferred form this total lipid extract (TLE) into an aqueous solution at low pH values (2.0--3.0). 3. At higher pH values (5.5) SP could be transferred from an aqueous phase into an organic phase (chloroform:methanol, 2:1) and recombined with TLE (which was previously freed from endogenous SP) contained in this phase. The binding capacity of TLE for SP exceeded by far the amount of endogenous SP bound originally in the brain extracts. 4. Among the lipids present in TLE, phosphatidylserine was able to bind and release SP in a pH dependent manner. 5. It is suggested that SP bound to phosphatidylserine is the storage form of SP in the brain. The mechanisms by which it is released are still unknown. The possibility that the SP-receptor is also a phospholipid is considered.

Animals↗

PubMed1994

Tsukuba high- and low-emotional strains of rats (Rattus norvegicus): an overview.

This report compiles the results of a series of studies on the Tsukuba High- and Low-Emotional strains (THE and TLE) of rats (Rattus norvegicus) established at the University of Tsukuba, Japan. The THE and TLE strains have been selected, respectively, for low and high activity in a runway test. During the course of selection, defecation has increased in the THE strain and decreased in the TLE strain. These strain differences were not affected by maternal influences, early experience, or psychotropic drugs. THE rats were consistently inactive in all novel situations examined, while TLEs were very active. The level of spontaneous activity, however, was similar between the two strains. It was remarkable that THE rats showed more burrowing activity than TLE animals, whereas the latter displayed more aggression than the former. Differences in learning ability, concentration of neural transmitters, and social behavior were examined.

Animals↗

PubMed1998

Monoamine oxidase B single-photon emission tomography with [123I]Ro 43-0463: imaging in volunteers and patients with temporal lobe epilepsy.

Imaging of monoamine oxidase of subtype B (MAO B) is of interest in various neurological diseases. In the past non-invasive assessment of MAO B has only been possible with positron emission tomography (PET) ligands. Given the limited availability of PET, a single-photon emission tomography (SPET) ligand would be desirable. In this study SPET imaging with the new MAO B inhibitor [123I]Ro 43-0463 was performed in five volunteers and nine patients with temporal lobe epilepsy (TLE). In two volunteers a second study was performed 12 h following blockade with deprenyl. In the TLE patients the tracer was administered as bolus (n = 4) or as prolonged infusion (n = 5). The regional uptake pattern correlated well with the known distribution of MAO B. In the two blocking studies ligand uptake was substantially reduced compared with baseline. In the TLE patients increased uptake was found in the ipsilateral mesial temporal lobe and, surprisingly, in the ipsilateral putamen. This study indicates the potential of the new SPET ligand [123I]Ro 43-0463 to map MAO B concentration in the human brain. The new finding of increased MAO B in the putamen of TLE patients needs further studies to elucidate its exact pathophysiology.

Adult↗

PubMed2001

Inter-modality comparisons of seizure focus lateralization in complex partial seizures.

Anterior temporal lobectomy offers a high chance of seizure-free outcome in patients suffering from drug-refractory complex partial seizure (CPS) originating from the temporal lobe. Other than EEG, several functional and morphologic imaging methods are used to define the spatial seizure origin. The present study was undertaken to compare the merits of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), magnetic resonance imaging (MRI) and single-voxel proton MR spectroscopy (MRS) for the lateralization of temporal lobe seizure foci. The clinical charts and imaging data of 43 consecutive CPS patients were reviewed. Based on surface EEG, 31 patients were classified with temporal lobe epilepsy (TLE; 25 lateralized, 6 not lateralized) and 12 with non-temporal lobe epilepsy. All were examined by FDG-PET, MRS and MRI within 6 weeks. FDG-PET and MRI were interpreted visually, while the N-acetyl-aspartate to creatine ratio was used for MRS interpretation. One FDG-PET scan was invalid due to seizure activity post injection. The MR spectra could not be evaluated in five cases bilaterally and three cases unilaterally for technical reasons. A total of 15 patients underwent anterior temporal lobectomy. All showed a beneficial postoperative outcome. When the proportions of agreement between FDG-PET (0.77), MRI (0.58) and MRS (0.56) and surface EEG in TLE cases were compared, there were no significant differences (P>0.10). However, FDG-PET showed a significantly higher agreement (0.93) than MRI (0.60; P=0.03) with the side of successful temporal lobectomy. The concordance of MRS with the side of successful temporal lobectomy was intermediate (0.75). When the results of functional and morphologic imaging were combined, no significant differences were found between the rates of agreement of FDG-PET/MRI and MRS/MRI with EEG (0.80 vs 0.68; P=0.50) and with the side of successful temporal lobectomy (0.87 vs 0.92; P=0.50) in TLE cases. However, MRS/MRI showed significantly more lateralized temporal lobe abnormalities in non-temporal lobe epilepsy cases than FDG-PET/MRI (0.90 vs. 0.17; P<0.01). Although FDG-PET seems to be the most reliable and stable method for this purpose, we conclude that in TLE cases it may be justified to perform MRS, which is less expensive, faster and has no radiation exposure, in combination with MRI before FDG-PET, since FDG-PET offers little additional diagnostic information if MRS and MRI indicate the same seizure focus lateralization.

Adolescent↗

PubMed2003

Cellular pathology of amygdala neurons in human temporal lobe epilepsy.

The amygdala complex substantially contributes to the generation and propagation of focal seizures in patients suffering from temporal lobe epilepsy (TLE). A cellular substrate for increased excitability in the human amygdala, however, remains to be identified. Here, we analyzed the three-dimensional morphology of 264 neurons from different subregions of the amygdaloid complex obtained from 17 "en bloc" resected surgical specimens using intracellular Lucifer Yellow (LY) injection and confocal laser scanning microscopy. Autopsy samples from unaffected individuals ( n=3, 20 neurons) served as controls. We have identified spine-laden, spine-sparse and aspinous cells in the lateral, basal, accessory basal and granular nuclei. Semiquantitative analysis points to significant changes in neuronal soma size, number of dendrites and spine densities in specimens from epilepsy patients compared to controls. Neuronal somata in the epilepsy group were smaller compared to controls ( P<0.01), neurons had fewer first-order dendrites ( P<0.01), whereas the maximum density of spines per dendritic segment in these cells was increased in TLE patients ( P<0.01). There were also dendritic alterations such as focal constrictions or spine bifurcations. These changes were consistent between amygdaloid subregions. The dendritic morphology of amygdaloid neurons in TLE patients points to substantial changes in synaptic connectivity and would be compatible with altered neuronal circuitries operating in the epileptic human amygdala. Although the morphological alterations differ from those described in hippocampal subregions of a similar cohort of TLE patients, they appear to reflect a characteristic pathological substrate associated with seizure activity/propagation within the amygdaloid complex.

Adult↗

PubMed1999

Bilateral reductions of hippocampal volume, glucose metabolism, and wada hemispheric memory performance are related to the duration of mesial temporal lobe epilepsy.

In refractory temporal lobe epilepsy (TLE) temporal lobe structures and functions are continuously or intermittently affected by abnormal brain electrical events, noxious neurochemical agents, and metabolic disturbances. There is conflicting evidence regarding the relationship between the duration of refractory mesial TLE and quantitative measures of temporal lobe functions and volumes of the hippocampi. Twenty patients (aged 28 +/- 7 years, 14 males) with an initial precipitating injury before the age of 5 years were subjected to high-resolution magnetic resonance imaging, fluoro-2-deoxy-d-glucose positron-emission tomography (PET), and the Wada test. We investigated whether the duration of unilateral refractory TLE (12 left, 8 right) affects hippocampal volume, glucose metabolism, or Wada hemispheric memory performance. Ipsilateral to the epileptogenic zone the hippocampal volume, metabolism, and Wada hemispheric memory performance were reduced compared to the corresponding contralateral measures. The duration of epilepsy controlled for age at investigation, side of seizure origin, underlying cause, and sex were negatively correlated with ipsi- and contralateral hippocampal volume, hippocampal metabolism, and Wada hemispheric memory performance. Moreover, ipsilateral Wada hemispheric memory performance and contralateral hippocampal glucose metabolism were correlated with the frequency of habitual seizures. Refractory TLE seems to be associated with a slow but ongoing bilateral temporal lobe damage. These cross-sectional results require verification by longitudinal studies carried out over a period of more than two decades.

Adolescent↗

PubMed2005

Effect of organic cosolvent on kinetic resolution of tert-leucine by penicillin G acylase from Kluyvera citrophila.

Penicillin G acylase (PGA) from Kluyvera citrophila immobilized on Amberzyml was used for enantioselective hydrolysis of N-phenylacetylated-DL-tert-leucine (N-Phac-DL-Tle) to produce L-tert-leucine (L-Tle). The effects of various organic cosolvents on hydrolysis of N-Phac-DL-Tle have been investigated in aqueous-cosolvent medium. It was founded that the rate of PGA-catalyzed reaction was significantly affected by the presence of 2% (v/v) organic cosolvent concentration. The initial rate fell with increasing logP of the cosolvent, but for logP values less than -0.24 the rate was faster than in purely aqueous medium. Additionally, the relative rate increases with the increase of dielectric constant (epsilon) of organic cosolvents. The yields of L-Tle in all aqueous-cosolvent systems were above 95% with the enantiomeric excess (ee) of >99%.

Enzyme Activation↗

PubMed1985

Autonomic responsiveness to affective visual stimulation in temporal lobe epilepsy.

Patients with temporal lobe epilepsy (TLE) have been posited by some to manifest a syndrome of interictal personality and behavioral change. Furthermore, this syndrome has been attributed to an underlying mechanism--enhanced affective responsiveness. The purpose of this investigation was to determine whether patients with TLE manifest increased emotional responsiveness relative to appropriate controls. Patients with TLE (n = 23) were compared with non-TLE (n = 7) and healthy controls (n = 16) as to their autonomic nervous system responsiveness to an emotionally stressing film. No differences were found among the groups. These results are related to the larger literature concerning epilepsy and psychopathology.

Adult↗

PubMed1996

Working memory in temporal lobe epilepsy: an event-related potential study.

Event-related potentials (ERPs) were recorded to a digit-probe identification and matching task (modified 'Sternberg paradigm') in 29 patients with temporal lobe epilepsy (TLE) and 26 healthy subjects. Our main aim was to identify the neurophysiological correlates of abnormal short term memory function in patients with TLE. Neuropsychological tests allowed the definition and comparison of two patient groups according to the presence or absence of memory dysfunction. These two groups did not differ significantly in mean age, education years, IQ, seizure duration, seizure frequency, anti-epileptic drug (AED) regimes, or on findings on neuroimaging. ERPs recorded under different levels of memory load were analysed both by conventional component identification and by an objective computer method of determining mean amplitudes of multiple 50 ms epochs (MMA analysis). We found that some significant abnormalities were common to both groups of patients; these included slow reaction times, a reduced amplitude of the N170 wave (and the corresponding 157-210 ms epoch in the MMA analysis) and a broad late negative shift between 577 and 735 ms. Other findings, including a significantly reduced performance accuracy as the level of memory load increased, were restricted to patients with abnormal memory function. The ERP changes that were specific to these patients occurred within a latency band of 200-420 ms and included a relatively preserved, but delayed P250 component and a delayed and attenuated N290 wave. When compared with either healthy subjects or with patients with normal memory, the responses in patients with abnormal memory showed an abnormal 'positive shift' between 262 and 315 ms after probe presentation and a further positive shift between 315 and 420 ms as memory load increased. These abnormalities of 'memory scanning' ERPs in patients with TLE which paralleled neuropsychological and behavioural evidence of memory dysfunction, and which occurred in the section of the response that is sensitive to memory loading in healthy subjects, provide further objective evidence that abnormalities of short term memory processes contribute to the memory deficits of TLE.

Adult↗

PubMed1996

Temporal lobe epilepsy: evidence for interictal uncoupling of blood flow and glucose metabolism in temporomesial structures.

Measurements of regional cerebral glucose metabolism (rCMRGlc) and blood flow (rCBF) are widely considered exchangeable for the detection of dysfunctional zones in temporal lobe epilepsy (TLE). However, the underlying assumption of preserved coupling of rCBF and rcMRGlc is questionable and requires verification. Thirteen patients with unilateral mesiolimbic TLE underwent interictal positron emission tomography (PET) measurements of rCBF using [15(O)]butanol and of rcMRGlc using (18)FDG. rcMRGlc, rCBF and glucose extraction fraction (rGEF) were obtained from temporomesial and temporolateral structures. When compared to the respective homotopic contralateral reference region, in temporomesial structures ipsilateral to the EEG-defined focus ('dysfunctional zone'), average rCMRGlc and rGEF were decreased while rCBF was unaffected. Analysis of (18)FDG kinetics revealed that (18)FDG transport was unaltered but the hexokinase reaction was specifically decreased. In the temporolateral structures, no such mismatch between metabolism and blood flow was observed. In mesiolimbic TLE, interictal rCMRGlc-PET is superior to rCBF-PET with respect to the sensitivity to detect regional functional abnormalities. This seems to be due to focal uncoupling of glucose metabolism and blood-brain barrier transport or blood flow. We hypothesize that the observed uncoupling of transport and metabolism may be characteristic of epileptogenic zones in TLE of typical etiology.

Adult↗

PubMed1990

Post-ictal recognition memory predicts laterality of temporal lobe seizure focus: comparison with post-operative data.

Standardized verbal and visuo-spatial memory recognition were obtained on 15 patients with unilateral temporal lobe epilepsy (TLE), using a reference group of 43 (12 males, 31 females) subjects with no previous history of neurological disease. Inter-ictal measures on these two tasks failed to differentiate between those patients with left vs right seizure foci. When eight of these patients were tested post-ictally (within 1 hr of seizure), seven showed the expected selective memory impairment when compared to inter-ictal performance. Left TLE patients showed a relative lowering of verbal memory, whereas patients with right TLE showed a relative visuo-spatial memory impairment. A similar result was also found in the patients when a comparison between pre-operative (inter-ictal) and post-operative performance was made, thereby further substantiating the validity of the tasks. This significant association between side of seizure focus and selective impairment of post-ictal memory performance provides evidence of a more direct method of neuropsychological diagnosis in TLE patients prior to surgery.

Adolescent↗

PubMed1994

P3 latency jitter assessed using 2 techniques. II. Surface and sphenoidal recordings in subjects with focal epilepsy.

We compared the latency variability in auditory P3s of 13 subjects with unilateral temporal lobe epilepsy (TLE) to that of normal controls. We predicted that increased latency jitter would occur in TLE subjects, particularly on the epileptic side. ERPs were recorded from scalp and sphenoidal sites relative to a balanced non-cephalic reference. Signal-to-noise ratios (SNRs) were calculated for each subject. Data were excluded if SNRs fell below 0.4. P3 latency jitter was estimated using 2 methods: Woody's algorithm and the maximum likelihood technique (MLT), a novel method of jitter assessment. SNRs were significantly higher in controls and were maximal posteriorly for both groups. P3 peak amplitude was significantly smaller in TLE subjects at temporal sites. Latency jitter (MLT method) was greatest in posterior sites and mirrored the jitter profiles of controls. Latency jitter was significantly higher in TLE subjects in bilateral frontal and temporal sites, but was not higher on the side of the focus and could not be attributed to lower SNRs. The increased bilateral latency jitter in these patients may be related to effects of anticonvulsants or the more extensive nature of the underlying epileptic disorder.

Adolescent↗

PubMed1995

Clinical applications: MRI, SPECT, and PET.

MRI, PET, and SPECT are all used to image abnormalities in the epileptic brain. Comparison of the techniques is difficult because they measure different aspects of the epileptic process--structure, metabolism, and perfusion. SPECT is the only one that can be systematically applied during seizures, while all three are used to image interictal abnormalities. Literature review suggests that of interictal techniques, PET has the highest diagnostic sensitivity in temporal lobe epilepsy (TLE) (84% vs. 66% for SPECT, 55% for qualitative MRI, 71% for quantitative MRI) while SPECT has the highest sensitivity in extratemporal epilepsy (ETE) (60% vs. 43% for MRI and 33% for PET). The highest diagnostic sensitivity and specificity were achieved by ictal imaging with SPECT (90% in TLE, 81% in ETE). The techniques, however, were not always redundant. One reason for the wide discrepancy of results in TLE and ETE might be the differing pathologic substrates. A literature review of imaging findings associated with mesial temporal sclerosis (MTS), developmental lesion or tumor as the underlying abnormality associated with epilepsy supports this explanation. PET and MRI are much more sensitive to MTS than SPECT (100%, 95% vs. 70%). On the other hand, in developmental lesions the three techniques are equally sensitive (88-92%) and in tumors, MRI was most sensitive (96%) and SPECT least (82%). A study at NIH explains the differing sensitivities: using PET to measure both blood flow and metabolism revealed discrepant findings in the same patients. Preliminary evidence also indicates that the distribution of hyperperfusion on ictal SPECT can differentiate subtypes of TLE. Combining the results of refined imaging techniques holds great promise in epilepsy localization and diagnosis.

Brain↗

PubMedDate not supplied

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↗

PubMed1995

Gypsy moth midgut proteinases: purification and characterization of luminal trypsin, elastase and the brush border membrane leucine aminopeptidase.

The principal digestive proteinases of the gypsy moth, Lymantria dispar, larval midgut were identified, and the subcellular distribution of the enzyme activities was determined. Proteinase activities of fifth-instar larvae were largely attributed to two luminal serine proteinases, a trypsin-like enzyme (TLE) and an elastase 2-like enzyme (ELA). TLE was purified to homegeneity by benzamidine-Sepharose affinity chromatography. With respect to size (M(r) = 25 kDa), substrate specificity, and interaction with trypsin inhibitors, the gypsy moth enzyme resembled mammalian pancreatic trypsin and trypsin-like enzymes from other insects. Gypsy moth elastase (ELA) was purified from the benzamidine-Sepharose flow-through by mono-Q FPLC. ELA exhibited a slightly smaller size (M(r) = 24 kDa) than TLE. The insect enzyme was inhibited by DFP and chymostatin but was unaffected by TPCK. ELA exhibited little esterolytic activity with BTEE. Succinyl-Ala-Ala-Pro-Leu p-nitroanilide was one of the best substrates for ELA, which is characteristic of elastase 2. TLE and ELA constituted c. 6% of the total soluble protein in midgut lumen of actively feeding fifth-instar larvae. Chymotrypsin and carboxypeptidase activities were not detected in any midgut fraction examined. The brush border membrane (BBM) leucine aminopeptidase (LAP) was isolated from CHAPS-solubilized BBM by FPLC. SDS-PAGE results indicated that the aminopeptidase has an apparent molecular size of c. 100 kDa. The aminopeptidase was inhibited by bestatin and was unaffected by serine proteinase inhibitors.

Amino Acid Sequence↗