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PubMed1993

The neuropathology of temporal lobe epilepsy.

Complex partial epilepsy arising in the temporal lobe has been associated with several types of pathologic lesions including Ammon's horn sclerosis, malformations, neoplasms, and inflammatory scars from infarcts or infection. These lesions are usually situated at various sites in the medial temporal lobe, so that one of the enigmas of attempting to understand the pathogenesis of TLE pertains to the clinical manifestation of a single epileptic disorder which is associated with dissimilar lesions at dissimilar sites. Recent demonstrations of an alteration in temporal lobe anatomy, i.e. malformations of the normal circuitry of the temporal lobe and foci of microdysgenesis, have given rise to the hypothesis that insults which occur during a critical period of brain development could alter the connections within the hippocampus and predispose it to increased excitability and seizurogenesis. Such a hypothesis forces us to reconsider TLE in reference to risk factors which may act as "teratogens" and produce these malformations. These malformations may range from a subtle alteration in the neurotransmitters of the dentate gyrus to large areas of cortical dysplasia or the hamartomatous neoplasms seen in TLE. A reevaluation of the neuroanatomical disruptions created by the various lesions may allow us to define a minimal optimal surgical resection for each lesion; or, the definitions of neurotransmitter deficits may lead to alternative pharmacologic therapies. As neuropathologists we have the exciting opportunity to participate in the definition of the neuropathology of temporal lobe epilepsy.

Animals↗

PubMed1998

Altered patterns of Ca2+/calmodulin-dependent protein kinase II and calcineurin immunoreactivity in the hippocampus of patients with temporal lobe epilepsy.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) and calcineurin represent neuronal Ca2+-dependent enzymes which dynamically modify several common substrates in the mammalian brain via phosphorylation/dephosphorylation cycles. Studies in animal models indicate that altered expression and activity of these enzymes may be involved in epilepsy. We have analyzed their immunohistochemical distribution in hippocampi of 28 temporal lobe epilepsy (TLE) patients and 13 controls. TLE specimens were classified as Ammon's horn sclerosis (AHS) or focal lesions without alteration of hippocampal cytoarchitecture. Compared to control and lesion-associated TLE specimens, striking changes in the distribution pattern of both enzymes were found in the dentate gyrus (DG) of AHS specimens: Whereas CaMKII labeling was significantly increased in the granule cell somata and their proximal dendrites, calcineurin immunoreactivity was significantly reduced in the granule cell somata. Furthermore, calcineurin staining in controls showed high levels in the inner molecular layer with a sharp demarcation towards the outer molecular layer. In AHS, calcineurin staining was reduced in the inner molecular layer, with partial loss of this demarcation. These findings raise the possibility, that an up-regulation of CaMKII with a concomitant down-regulation of calcineurin in the DG of AHS specimens may cause a pathogenetically relevant imbalance of neuronal Ca2+/calmodulin-dependent phosphorylation/dephosphorylation systems.

Adult↗

PubMedDate not supplied

Electric source imaging in temporal lobe epilepsy.

The objective of this study was to determine the validity of interictal spike (IIS) source localization in temporal lobe epilepsies (TLE) using stereoelectroencephalography as a validating method. Twenty patients with drug-resistant TLE were studied with high-resolution EEG and stereoelectroencephalography. Sixty-four scalp channels, a realistic head model, and different algorithms were used. For each patient, the intracerebral interictal distribution was studied and classified into one of three groups: L (mainly lateral), ML (mediolateral), and M (medial). In group L (three patients), surface IIS were recorded with a high signal-to-noise ratio. Source localizations designated all or part of the intracerebral interictal distribution. In group ML (11 patients), 8 patients had surface IIS, only 5 of which were localizable. High-resolution EEG permitted localization of the more lateral portion and definition of its rostrocaudal extension. A common pattern was identified in three patients with a predominant role of the temporal pole. In group M (six patients), four patients had rare surface IIS, none of which were localizable. Surface EEG does not record IIS limited to medial temporal lobe structures. In TLE with a mediolateral or a lateral interictal distribution, only the lateral component is detectable on surface EEG and accurately localizable by source localization tools.

Adolescent↗

PubMed2004

Striking differences in individual anticonvulsant response to phenobarbital in rats with spontaneous seizures after status epilepticus.

PURPOSE: More than one third of patients with epilepsy have inadequate control of seizures with drug therapy, but mechanisms of intractability are largely unknown. Because of this large number of pharmacoresistant patients with epilepsy, the existing process of antiepileptic drug (AED) discovery and development must be reevaluated with a focus on preclinical models of therapy-resistant epilepsy syndromes such as mesial temporal lobe epilepsy (TLE). However, although various rodent models of TLE are available, the pharmacoresponsiveness of most models is not well known. In the present study, we used a post-status epilepticus model of TLE to examine whether rats with spontaneous recurrent seizures (SRSs) differ in their individual responses to phenobarbital (PB). METHODS: Status epilepticus was induced in Sprague-Dawley rats by prolonged electrical stimulation of the basolateral amygdala. Once the rats had developed SRSs, seizure frequency and severity were determined by continuous EEG/video recording over a 6-week period (i.e., a predrug control period of 2 weeks, followed by PB treatment for 2 weeks, and a postdrug control period of 2 weeks). PB was administered twice daily at maximal tolerated doses. RESULTS: Analysis of plasma drug concentrations showed that drug concentrations within the therapeutic range (10-40 microg/ml) were maintained in all rats throughout the period of treatment. In six (55%) of 11 rats, complete control of seizures was achieved, and another rat exhibited a >90% reduction of seizure frequency. These seven rats were considered responders. The remaining four (36%) rats showed either no response at all (n=3) or only moderate reduction in seizure frequency and were therefore considered nonresponders. Plasma drug concentrations did not differ between these two groups of rats. CONCLUSIONS: These data demonstrate that, similar to patients with epilepsy, rats with SRSs markedly differ in their individual responses to AED treatment. Pharmacoresistant rats selected by prolonged drug treatment from groups of rats with SRSs may provide a unique model to study mechanisms of pharmacoresistance and to identify novel AEDs for treating seizures of patients currently not controlled with existing therapies.

Amygdala↗

PubMed2004

Usefulness of [11C]methionine PET in the diagnosis of dysembryoplastic neuroepithelial tumor with temporal lobe epilepsy.

PURPOSE: We assessed the diagnostic value of [11C]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE). METHODS: This series consisted of seven TLE patients with benign tumors in the temporal lobe. After MET-PET study, all seven patients underwent tumor resection along with focus excision. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV). We also assessed the relation between MET uptake and proliferation capacity observed in the surgical specimens. RESULTS: Whereas four patients with DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake lesions. In the DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to 1.14. MET uptake was significantly lower in the patients with DNETs than in the patients with ganglioglioma and brain gliomas (SUV, p = 0.045; L/C ratio, p = 0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher labeling index was not related to high MET uptake based on the SUV (p = 0.91) and L/C ratio (p = 0.38). CONCLUSIONS: Negative MET uptake in benign temporal lobe tumors with TLE is consistent with a preoperative diagnosis of DNET.

Adolescent↗

PubMed2004

Regional cerebral hyperperfusion with ictal dystonic posturing: ictal-interictal SPECT subtraction.

PURPOSE: Ictal-interictal single-photon emission computed tomography (SPECT) subtraction was performed to find brain structures related to ictal dystonic posturing (DP) in patients with temporal lobe epilepsy (TLE). METHODS: Thirty-two patients with mesial TLE who had ictal and interictal SPECTs were included. They were divided into two groups; DP group with ictal dystonia during ictal SPECT (n = 15) and Non-DP group without ictal DP (n = 17). Ictal-interictal SPECT subtraction was performed, and then subtracted SPECT was coregistered with brain spoiled gradient recalled (SPGR) magnetic resonance imaging (MRI). The ictal hyperperfusion on subtracted SPECT was analyzed in basal ganglia, frontal cortex, thalamus, temporal lobe, and insular cortex. RESULTS: The incidences of ictal hyperperfusion on brain regions in DP versus Non-DP groups were 80.0% (12 of 15 patients) versus none (0 of 17), p = 0.001, chi2, in caudate nucleus; 93.3% (14 of 15) versus 47.0% (eight of 17), p = 0.005, in putamen; and 80.0% (12 of 15) versus 41.2% (seven of 17), p = 0.026, in thalamus. No significant difference of ictal hyperperfusion was found in globus pallidus, temporal lobes, insular and frontal cortices between DP and Non-DP groups. DP patients showed an earlier age at seizure onset [8.6 years (DP) vs. 15.7 years (Non-DP) (p = 0.015)] and a longer duration of seizure history [19.0 years (DP) vs. 11.9 years (Non-DP) (p = 0.015)]. CONCLUSIONS: Caudate nucleus, putamen, and thalamus were significantly related to the ictal DP during TLE seizures. Our study showed first an active involvement of the caudate nucleus in the generation of ictal DP.

Basal Ganglia↗

PubMed2004

The application of functional MRI of memory in temporal lobe epilepsy: a clinical review.

Functional MRI (fMRI) is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions. Since its introduction, there has been considerable speculation regarding the role it may play in the presurgical assessment of temporal lobe epilepsy (TLE). This review considers the progress made to date in using fMRI to investigate memory processing in the medial temporal lobe in normal subjects and in those with TLE. Results so far suggest that fMRI will be incorporated into the presurgical assessment of TLE in the coming years to improve definition of eloquent cerebral areas, with the objective of minimizing the adverse cognitive sequelae of anterior temporal lobe resection.

Brain Mapping↗

PubMed2004

Genital automatisms: a video-EEG study in patients with medically refractory seizures.

PURPOSE: Genital automatisms (GAs) are rare clinical phenomena during or after epileptic seizures. They are defined as repeated fondling, grabbing, or scratching of the genitals. The anatomic correlates of GAs have been discussed controversially. The aim of this investigation was to assess the localizing and lateralizing value of GAs. METHODS: The authors studied 207 consecutive patients with intractable seizures referred to a University Hospital for presurgical evaluation between 1998 and 2002: 135 had temporal lobe epilepsy (TLE); 23, frontal lobe epilepsy (FLE); 29, generalized epilepsies (GEs); and 20 had extratemporal or multifocal epilepsy. RESULTS: Twenty-three (11%) of 207 patients showed GAs in 42 (3%) of 1,299 seizures. GAs occurred significantly more often in men (17 of 93, 18%) than in women (six of 114, 5%; p = 0.0037). Twenty-one (16%) of 135 patients with TLE performed GAs, one (4%) of 23 with FLE and one (3%) of 29 with GE. GAs were associated with unilateral hand automatisms in 16 (70%) of 23 and with periictal urinary urge in five (22%) of 23. All patients had amnesia for the performance of GAs. CONCLUSIONS: GAs appear in the ictal or postictal period with impaired consciousness. Men exhibit GAs significantly more often than do women. GAs do not localize or lateralize per se, but may localize seizure onset in the presence of periictal urinary urge or unilateral hand automatisms. They show a tendency to occur more often in TLE.

Adolescent↗

PubMed2004

Seizure outcome after anterior temporal lobectomy and its predictors in patients with apparent temporal lobe epilepsy and normal MRI.

PURPOSE: Very little reliable information is available regarding the role of anterior temporal lobectomy (ATL), optimal presurgical evaluation strategy, post-ATL seizure outcome, and the factors that predict the outcome in patients with medically refractory temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI). To be cost-effective, epilepsy surgery centers in developing countries will have to select candidates for epilepsy surgery by using the locally available technology and expertise. METHODS: We reviewed the electroclinical and pathological characteristics and seizure outcome of 17 patients who underwent ATL for medically refractory TLE after being selected for ATL based on a noninvasive selection protocol without the aid of positron emission tomography (PET) or single-photon emission computed tomography (SPECT), despite a normal preoperative high-resolution MRI. RESULTS: Seven (41%) patients achieved an excellent seizure outcome; five of them were totally seizure free. An additional five (29%) patients had >75% reduction in seizure frequency. The following pre-ATL factors predicted an excellent outcome: antecedent history of febrile seizures, strictly unilateral anterior temporal interictal epileptiform discharges (IEDs), and concordant type 1 ictal EEG pattern. All the five patients with pathologically verified hippocampal formation neuronal loss were seizure free. The presence of posterior temporal, bilateral temporal, and generalized IEDs portended unfavorable post-ATL seizure outcome. CONCLUSIONS: A subgroup of patients destined to have an excellent post-ATL outcome can be selected from MRI-negative TLE patients by using history and scalp-recorded interictal and ictal EEG data. The attributes of these patients are antecedent history of febrile seizures, strictly unilateral anterior IEDs, and concordant type 1 ictal EEG pattern.

Adolescent↗

PubMed2004

Clinical manifestations of insular lobe seizures: a stereo-electroencephalographic study.

PURPOSE: In this study, we report the clinical features of insular lobe seizures based on data from video and stereo-electroencephalographic (SEEG) ictal recordings and direct electric insular stimulation of the insular cortex performed in patients referred for presurgical evaluation of temporal lobe epilepsy (TLE). METHODS: Since our first recordings of insular seizures, the insular cortex has been included as one of the targets of stereo-electroencephalographic (SEEG) electrode implantation in 50 consecutive patients with TLE whose seizures were suspected to originate from, or rapidly to propagate to, the perisylvian cortex. In six, a stereotyped sequence of ictal symptoms associated with intrainsular discharges could be identified. RESULTS: This ictal sequence occurred in full consciousness, beginning with a sensation of laryngeal constriction and paresthesiae, often unpleasant, affecting large cutaneous territories, most often at the onset of a complex partial seizure (five of the six patients). It was eventually followed by dysarthric speech and focal motor convulsive symptoms. The insular origin of these symptoms was supported by the data from functional cortical mapping of the insula by using direct cortical stimulations. CONCLUSIONS: This sequence of ictal symptoms looks reliable enough to characterize insular lobe epileptic seizures (ILESs). Observation of this clinical sequence at the onset of seizures on video-EEG recordings in TLE patients strongly suggests that the seizure-onset zone is located not in the temporal but in the insular lobe; recording directly from the insular cortex should occur before making any decision regarding epilepsy surgery.

Adult↗

PubMed2005

ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy.

PURPOSE: To clarify the possible role of other factors including the ApoE epsilon4 allele for memory decline in temporal lobe epilepsy (TLE). METHODS: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD +/- 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, +/-21.7), and the mean duration of epilepsy was 17.1 years (SD, +/-15.7). RESULTS: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE epsilon4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66-10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration > or =25.5 years (OR, 7.06; 95% CI, 1.67-29.85), especially if they carried the epsilon4 allele (OR, 32.29; 95% CI, 5.23-195.72). CONCLUSIONS: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.

Adolescent↗

PubMed2005

Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral temporal lobe epilepsy and their clinical correlates.

PURPOSE: To assess the presence, extent, and clinical correlates of quantitative MR volumetric abnormalities in ipsilateral and contralateral hippocampus, and temporal and extratemporal lobe regions in unilateral temporal lobe epilepsy (TLE). METHODS: In total, 34 subjects with unilateral left (n = 15) or right (n = 19) TLE were compared with 65 healthy controls. Regions of interest included the ipsilateral and contralateral hippocampus as well as temporal, frontal, parietal, and occipital lobe gray and white matter. Clinical markers of neurodevelopmental insult (initial precipitating insult, early age of recurrent seizures) and chronicity of epilepsy (epilepsy duration, estimated number of lifetime generalized seizures) were related to magnetic resonance (MR) volume abnormalities. RESULTS: Quantitative MR abnormalities extend beyond the ipsilateral hippocampus and temporal lobe with extratemporal (frontal and parietal lobe) reductions in cerebral white matter, especially ipsilateral but also contralateral to the side of seizure onset. Volumetric abnormalities in ipsilateral hippocampus and bilateral cerebral white matter are associated with factors related to both the onset and the chronicity of the patients' epilepsy. CONCLUSIONS: These cross-sectional findings support the view that volumetric abnormalities in chronic TLE are associated with a combination of neurodevelopmental and progressive effects, characterized by a prominent disruption in ipsilateral hippocampus and neural connectivity (i.e., white matter volume loss) that extends beyond the temporal lobe, affecting both ipsilateral and contralateral hemispheres.

Adolescent↗

PubMed1996

A method of estimating tooth life expectancy.

One of the most important outcome measures for dental services is the increase in tooth life expectancy which is brought about by the interventions provided. Thus, a convenient and accurate index of tooth survival is critical both to clinical decision making and to more general assessments of public dental health policies. This paper describes a simple method of approximating tooth life expectancy (TLE). The method is based on the assumption that tooth survival follows a simple declining exponential function. Assuming a constant mortality rate, TLE is the integral of the survival function, expressed as S(t) = e-mu t, where t is time and mu the constant mortality rate. Using 3-year tooth-specific mortality rates for 491 subjects aged 50 years or more, tooth-specific life expectancies for the population as a whole where found to range from 27 years for upper canines to 71 years for lower incisors. Individuals with a mean periodontal attachment loss greater than 4 mm and people on low incomes had significantly lower tooth life expectancies than their periodontally fit and more wealthy counterparts. This technique can be used to obtain disease-specific or intervention-specific tooth life expectancies. Thus, gains in TLE for individuals with different oral, social and behavioural characteristics can be calculated. The declining exponential approximation of tooth life expectancy has the potential to become a powerful tool in the evaluation of dental services and treatments.

Cuspid↗

PubMed1976

A morphological study on vascular changes in the surgically resected tissues of temporal lobe epilepsy-with a special reference to the etiology.

(1) Twenty-one out of 23 cases surgically resected specimens of TLE presented the common histological findings; sclerotic changes of the tissues. And the other two cases encountered the small tumors which might be called "cryptic". (2) Since circulatory disturbance is generally accepted to explain the cause of TLE we reexamined vascular behaviors in detail and found the quantitative and qualitative abnormaltities which reached the high rate of 71% (17 out of 21 cases) except two cases of small tumors. Moreover, it is remarkably noteworthy that these vascular changes adjoin the sclerosed parenchymal tissue. (3) It may be said that vascular changes have exerted some influences on the formation of inferomedial temporal sclerosis from the standpoint of the histological findings, though they are alone not fully sufficient to explain the etiology of TLE.

Brain Neoplasms↗

PubMed1986

Personality and neuropsychological aspects of temporal lobe epileptics and schizophrenics.

The present study was designed to ascertain and explore whether distinct personality profiles and neuropsychological features characterized temporal lobe epilepsy (TLE) vs. schizophrenic patients (Sc). The subjects were 20 epileptics and 19 schizophrenics matched with an overall IQ. They underwent various personality and neuropsychological tests. These results showed that the personality of the left-TLE patients tended to be more sensitive, aggressive, hostile and emotionally labile than the right-TLE and Sc patients. Finally, the Sc patients showed poor performance in verbal and nonverbal delayed tasks, especially on the right visual hemifield ones. These results suggested that they have the frontal lobe dysfunction, especially of the left hemisphere.

Adolescent↗

PubMed2005

Anterior perirhinal cortex kindling produces long-lasting effects on anxiety and object recognition memory.

Temporal lobe epilepsy (TLE) is frequently accompanied by memory impairments and, although their bases are unknown, most research has focused on the hippocampus. The present study investigated the importance of another medial temporal lobe structure, the perirhinal cortex (Prh), in changes in memory in TLE using kindling as a model. Rats were kindled twice daily with anterior Prh stimulation until three fully generalized seizures were evoked. Beginning 7 days later and on successive days, rats were tested in an elevated plus maze, a large circular open field, an open field object exploration task and a delayed-match-to-place task in a water maze in order to assess anxiety-related and exploratory behaviour, object recognition memory and spatial cognition. Kindling increased anxiety-related behaviour in both the elevated plus and open field mazes and disrupted spontaneous object recognition but spared all other behaviours tested. These results are consistent with other findings indicating a greater role for the Prh in object memory and emotional behaviour than in spatial memory and contrast with the selective disruption of spatial memory produced by dorsal hippocampal kindling. The site-selectivity of the behavioural disruptions produced by kindling indicates that such effects are probably mediated by changes particular to the site of seizure initiation rather than to changes in the characteristic circuitry activated by limbic seizure generalization. Further investigation of the behavioural effects of Prh kindling may be useful for studying the mechanisms of mnemonic and affective dysfunction associated with TLE and offer insights into bases for variability in such dysfunction across patients.

Animals↗

PubMed2005

Disruption of the neurogenic potential of the dentate gyrus in a mouse model of temporal lobe epilepsy with focal seizures.

Adult hippocampal neurogenesis is enhanced in response to multiple stimuli including seizures. However, the relationship between neurogenesis and the development of temporal lobe epilepsy (TLE) remains unclear. Unilateral intrahippocampal injection of kainate in adult mice models the morphological characteristics (e.g. neuronal loss, gliosis, granule cell dispersion and hypertrophy) and occurrence of chronic, spontaneous recurrent partial seizures observed in human TLE. We investigated the influence of a kainate-induced epileptogenic focus on hippocampal neurogenesis, comparing neural stem cell proliferation following status epilepticus and spontaneous recurrent partial seizures. Cell proliferation in the subgranular zone was transiently increased bilaterally after kainate treatment. As a result, neurogenesis was stimulated in the contralateral dentate gyrus. In contrast, the epileptic hippocampus exhibited a strongly reduced neurogenic potential, even after onset of spontaneous recurrent partial seizures, possibly due to an alteration of the neurogenic niche in the subgranular zone. These results show that neurogenesis does not contribute to the formation of the epileptic focus and may be affected when dispersion of dentate gyrus granule cells occurs. Therefore, in patients with TLE, hippocampal sclerosis and granule cell dispersion may play a significant role in disrupting the potential for hippocampal neurogenesis.

Animals↗

PubMed2005

Reorganization of language-related neuronal networks in patients with left temporal lobe epilepsy - an fMRI study.

To investigate the inter- and intrahemispheric reorganization of the language cortex in left temporal lobe epilepsy (TLE) with left-sided hippocampal sclerosis. A functional magnetic resonance imaging was performed on 13 right-handed patients suffering from medically intractable left TLE, and in 13 sex- and age-matched healthy controls. The activation paradigm used was a silent word generation task. A language laterality index (LI) was calculated from the number of activated voxels in the right and left anterior two-thirds of the hemispheres. Significant differences between the patients and the controls were observed in the activation of the left-sided inferior frontal gyrus. Less consistent findings in this region, as well as the relative protection of Broca's area from the activation, were revealed in the patients. In addition, different patterns of activation were proven in the cerebellum and other cortical as well as subcortical brain structures within both hemispheres. Significant differences were also found in the values of the language LIs between the investigated groups: these values suggested a more bihemispheric language representation in the patients. As anticipated, lateralization of the language functions in the epileptics significantly decreased in connection with an earlier age of initial insult. Our results support the hypothesis of a significant intra- and interhemispheric functional reorganization of language-related neuronal networks in left TLE.

Adult↗