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PubMed2001

Distinguishing subtypes of temporal lobe epilepsy with background hippocampal activity.

PURPOSE: Two subtypes of temporal lobe epilepsy (TLE) can be defined through clinical observations and analysis of hippocampal tissue resected during surgical procedures for intractable TLE: (a) mesial temporal sclerosis (MTS), which is characterized by extensive changes to the hippocampus and good surgical outcome; and (b) paradoxical temporal lobe epilepsy (PTLE), which is characterized by minimal cell loss and comparatively poorer surgical outcome. Patients in both subtypes have seizures that appear to begin in the medial temporal lobe, but documented differences in substrate and outcome between these subtypes has defined a need to distinguish MTS and PTLE patients before surgery. This report describes a retrospective study to investigate the feasibility of doing so during intracranial monitoring. METHODS: Background EEG epochs, 5 min in duration, were recorded from the anterior hippocampus in 14 (10 MTS and four PTLE) patients with consistent localization of seizure onset to medial temporal structures. The power spectral density (PSD) of the EEG epochs was calculated by a Fourier spectral estimator, and the total signal power and power of the delta, theta, alpha, beta, and gamma frequency bands were submitted to group-to-group comparison. RESULTS: Spectral peaks were observed in the delta band in all PSD estimates and in the theta band in nine of 14 (seven MTS, two PTLE) estimates. The MTS and PTLE subtypes could be distinguished by the total signal power and delta band power. These power measurements were greater in the PTLE subtype. CONCLUSIONS: Both delta and theta spectral components are present in hippocampal background EEGs recorded from patients with TLE. The results indicate that group differences exist in spectral measures of background hippocampal signals recorded from MTS and PTLE subtypes. This suggests both that substrate differences in cellular composition and connectivity are reflected in hippocampal background EEGs and that spectral measurements of these signals may hold promise for tests to identify the group membership of individual patients.

Adult↗

PubMed2001

Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring.

PURPOSE: To investigate antiepileptic drug (AED) withdrawal during video-EEG monitoring in adult patients with temporal lobe epilepsy (TLE). METHODS: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4-6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS). RESULTS: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16-451 h) was required for completing the monitoring in each patient. Forty-three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal. CONCLUSIONS: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video-EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.

Adolescent↗

PubMed2001

Lack of association between an interleukin 1 beta (IL-1beta) gene variation and refractory temporal lobe epilepsy.

PURPOSE: We attempted to confirm recent findings of Kanemoto et al. that demonstrated a positive association (p < 0.017) between a polymorphism in the promoter region of the interleukin 1-beta (IL-1beta) gene and the clinical phenotype of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS). METHODS: We determined the frequency of this polymorphism in a group of 61 TLE+HS patients of European ancestry and compared it with that found in 119 ethnically matched control subjects. RESULTS: Analysis of genotype and allele frequencies showed no statistically significant difference in the distribution of the polymorphism between the two groups (p = 0.10). CONCLUSIONS: These data suggest that this IL-1beta promoter polymorphism does not act as a strong susceptibility factor for TLE+HS in a population of individuals of European ancestry.

Epilepsy, Temporal Lobe↗

PubMed2001

Lateralized postictal EEG delta predicts the side of seizure surgery in temporal lobe epilepsy.

PURPOSE: The concordance of lateralized EEG postictal polymorphic delta activity (PPDA) to the side of seizure origin in temporal lobe epilepsy (TLE) has received limited study. Our objective was to study the lateralizing value of PPDA in patients with documented TLE. METHODS: A cohort of consecutive adults with TLE, detailed presurgical evaluation before temporal lobectomy, and minimal follow-up of 2 years were included. One author masked the ictal rhythm of presurgical EEGs and randomly presented 20 s of preictal and the postictal EEG to two electroencephalographers who were blind to all clinical data. They independently assigned PPDA to one of three categories: not present, bilateral, or lateralized (defined as newly appearing or an amplitude >50% of the preictal record). RESULTS: Eighty seizures from 29 patients were studied. Fifteen patients had a left, and 14 had a right temporal lobectomy. Twenty-three patients were seizure free or substantially improved (defined as simple partial or nocturnal seizures only). Lateralized PPDA was present in 64% of all EEGs and at least one record from 22 (76%) patients. Lateralized PPDA, when present, was concordant with the side of surgery in 96% of the EEGs. CONCLUSIONS: Lateralized PPDA is highly predictive of the side of ultimate temporal lobectomy, and by inference the side of seizure origin.

Adolescent↗

PubMed2002

Metabolic and electrophysiological alterations in subtypes of temporal lobe epilepsy: a combined proton magnetic resonance spectroscopic imaging and depth electrodes study.

PURPOSE: This study compared the metabolic regional alterations, characterized by proton magnetic spectroscopic imaging ((1)H-MRSI), with electrophysiological abnormalities recorded by using depth electrodes and with structural lesions, in patients with several subtypes of temporal lobe epilepsy (TLE). METHODS: Twenty-five subjects were investigated, including 15 controls and 10 patients with drug-resistant unilateral TLE, nine of whom had structural abnormalities identified by MRI. All patients underwent noninvasive presurgical evaluation and then stereoelectroencephalography (SEEG). We performed an original metabolic exploration combining two (1)H-MRS imaging acquisitions associated with two single-voxel acquisitions (temporal poles) to map the most informative regions of interest (ROIs) including mesial and neocortical localizations. The N-acetyl aspartate/(choline+creatine) ratio was chosen as a metabolic index. SEEG analysis allowed the classification of each ROI as electrically normal or abnormal (i.e., involved in ictal and/or interictal discharges). Groups were compared by using a nonparametric Mann-Whitney U test. RESULTS: N-Acetyl aspartate/(choline+creatine) was significantly lower in all regions involved in SEEG electrophysiological epileptic abnormalities than in controls (p < 0.05). In contrast, the regions without any electrophysiological abnormalities were not metabolically different from those in controls (p > 0.05) except in one ROI. No differences between the metabolic profiles of epileptogenic and irritative zones were found. The metabolic alterations included, but also extended beyond, the lesions. The presence of metabolic abnormalities in mesial structures was not specific for the mesial subtype and generally extended outside the mesial structures. CONCLUSIONS: These results indicate that metabolic abnormalities are linked to ictal and interictal epileptiform activities rather than to structural alterations in TLE.

Adolescent↗

PubMed2002

Surgical implications of neuromagnetic spike localization in temporal lobe epilepsy.

PURPOSE: To investigate the clinical usefulness of magnetoencephalography (MEG) as a guide to the surgical treatment of temporal lobe epilepsy (TLE). METHODS: Preoperative spike localization by MEG was compared with seizure outcome and postoperative spike localization at 12 months after resective surgery in 16 patients with TLE. Spike localization was classified into anterior temporal (AT) and non-AT localization in 11 patients without neocortical lesion treated with anterior temporal lobectomy (ATL); and lesion and lobar localization in five patients with neocortical lesion treated with lesionectomy (n = 3) or lesionectomy with medial temporal resection (n = 2). RESULTS: All five patients with AT localization became seizure free and spike free after surgery. Among the six patients with non-AT localization, two became seizure free and spike free, two became seizure free with residual spikes, one had residual seizures but no spikes, and one had both residual seizures and spikes. All three patients with lesion localization and two with lobar localization had favorable seizure outcome and became spike free after surgery. CONCLUSIONS: MEG spike localization can identify neocortical sources remote from the presumed epileptogenic area. Favorable seizure outcome can be expected in patients with AT localization after ATL and patients with lesion localization after lesionectomy. In contrast, non-AT localization indicates either nonmedial TLE or spike propagation to the posterior and extratemporal neocortex. Similarly, lobar localization indicates spike propagation from an epileptogenic lesion or extensive epileptogenicity. Patients with non-AT localization or lobar localization should undergo intensive evaluations, such as intracranial EEG, for improved seizure outcome.

Action Potentials↗

PubMed2002

Expression of the multidrug transporter P-glycoprotein in brain capillary endothelial cells and brain parenchyma of amygdala-kindled rats.

PURPOSE: Based on data from brain biopsy samples of patients with pharmacoresistant partial epilepsy, overexpression of the multidrug transporter P-glycoprotein (PGP) in brain capillary endothelium has recently been proposed as a potential mechanism of resistance to antiepileptic drugs (AEDs). We examined whether PGP is overexpressed in brain regions of amygdala-kindled rats, a widely used model of temporal lobe epilepsy (TLE), which is often resistant to AEDs. METHODS: Rats were kindled by stimulation of the basolateral amygdala (BLA); electrode-implanted but nonkindled rats and naive (not implanted) rats served as controls. PGP was determined by immunohistochemistry either 1 or 2 weeks after the last kindled seizure, by using a monoclonal anti-PGP antibody. Six brain regions were examined ipsi- and contralateral to the BLA electrode: the BLA, the hippocampal formation, the piriform cortex, the substantia nigra, the frontal and parietal cortex, and the cerebellum. RESULTS: In both kindled rats and controls, PGP staining was observed mainly in microvessel endothelial cells and, to a much lesser extent, in parenchymal cells. The distribution of PGP expression across brain regions was not homogeneous, but significant differences were found in both the endothelial and parenchymal expression of this protein. In kindled rats, ipsilateral PGP expression tended to be higher than contralateral expression in several brain regions, which was statistically significant in the piriform cortex and parietal cortex. However, compared with controls, no significant overexpression of PGP in capillary endothelial cells or brain parenchyma of kindled rats was seen in any ipsilateral brain region, including the BLA. For comparison with kindled rats, kainate-treated rats were used as positive controls. As reported previously, kainate-induced seizures significantly increased PGP expression in the hippocampus and other limbic brain regions. CONCLUSIONS: Amygdala-kindling does not induce any lasting overexpression of PGP in several brain regions previously involved in the kindling process. In view of the many pathophysiologic and pharmacologic similarities between the kindling model and TLE, these data may indicate that PGP overexpression in pharmacoresistant patients with TLE is a result of uncontrolled seizures but not of the processes underlying epilepsy. It remains to be determined whether transient PGP overexpression is present in kindled rats shortly after a seizure, and whether pharmacoresistant subgroups of kindled rats exhibit an increased expression of PGP. Furthermore, other multidrug transporters, such as multidrug resistance-associated protein, might be involved in the resistance of kindled rats to AEDs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

A short-echo-time proton magnetic resonance spectroscopic imaging study of temporal lobe epilepsy.

PURPOSE: We used short-echo-time proton magnetic resonance spectroscopy imaging (MRSI) to study metabolite concentration variation through the temporal lobe in patients with temporal lobe epilepsy (TLE) with and without abnormal MRI. METHODS: MRSI was performed at TE = 30 ms to study 10 control subjects, 10 patients with TLE and unilateral hippocampal sclerosis, and 10 patients with TLE and unremarkable MRI (MRI negative). We measured the concentrations of N-acetyl aspartate +N-acetyl aspartyl-glutamate (NAAt), creatine (Cr), choline (Cho), glutamate + glutamine (Glx), and myoinositol, in the anterior, middle, and posterior medial temporal lobe (MTL), and in the posterior lateral temporal lobe. Segmented volumetric T1-weighted MRIs gave the tissue composition of each MRSI voxel. Normal ranges were defined as the control mean +/- 3 SD. RESULTS: In the hippocampal sclerosis group, seven of 10 had abnormally low NAAt in the ipsilateral anterior MTL. In the MRI-negative group, four of 10 had low NAAt in the middle MTL voxel ipsilateral to seizure onset. Metabolite ratios were less sensitive to abnormality than was the NAAt concentration. Group analysis showed low NAAt, Cr, and Cho in the anterior MTL in hippocampal sclerosis. Glx was elevated in the anterior voxel contralateral to seizure onset in the MRI-negative group. Metabolite concentrations were influenced by voxel position and tissue composition. CONCLUSIONS: (a) Low NAAt, Cr, and Cho were features of the anterior sclerotic hippocampus, whereas low NAAt was observed in the MRI-negative group in the middle MTL region. The posterior temporal lobe regions were not associated with significant metabolite abnormality; (b) The two patient groups demonstrated different metabolite profiles across the temporal lobe, with elevated Glx a feature of the MRI-negative group; and (c) Voxel tissue composition and position influenced obtained metabolite concentrations.

Adult↗

PubMed2003

Ictal magnetoencephalography in temporal and extratemporal lobe epilepsy.

PURPOSE: We evaluated visual patterns and source localization of ictal magnetoencephalography (MEG) in patients with intractable temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETE). METHODS: We performed spike and seizure recording simultaneously with EEG and MEG on two patients with TLE and five patients with ETE. Scalp EEG was recorded from 21 channels (10-20 international system), whereas MEG was recorded from two 37-channel sensors. We compared ictal EEG and MEG onset, frequency, and evolution and performed MEG dipole source localization of interictal spikes and early ictal discharges and co-registered dipoles to brain magnetic resonance imaging (MRI). We correlated dipole characteristics with intracranial EEG, surgical resection, and outcome. RESULTS: Ictal MEG lateralized seizure onset in both TLE patients and demonstrated ictal onset, frequency, and evolution in accordance with EEG. Ictal MEG source analysis revealed tangential vertical dipoles in the anterolateral angle in one patient, and anterior dipoles with anteroposterior orientation in the other. Intracranial EEG revealed regional entorhinal seizure onset in the first patient. Both patients became seizure free after temporal lobectomy. In ETE, ictal MEG demonstrated visual patterns similar to ictal EEG and had concordant localization with interictal MEG in all five patients. Two patients underwent surgery. Ictal MEG localization was concordant with intracranial EEG in both cases. One patient had successful outcome after surgery. The second patient did not improve after limited resection and multiple subpial transections. CONCLUSIONS: Ictal MEG can demonstrate ictal onset frequency and evolution and provide useful localizing information before epilepsy surgery.

Electroencephalography↗

PubMed2003

Olfactory auras in patients with temporal lobe epilepsy.

PURPOSE: To investigate olfactory auras in patients with temporal lobe epilepsy (TLE). METHODS: We reviewed medical records of 217 Chinese patients who underwent temporal lobectomy for medically intractable TLE between 1987 and 1998 in Taiwan. Patients with olfactory auras asked for detailed characteristics of their auras. RESULTS: In all, 12 (5.5%) patients had olfactory auras, seven men and five women. All patients except one described and characterized the unpleasant olfactory auras. Olfactory auras were usually combined with other auras, most frequently sensations of epigastric rising, nausea, and fear. Association with gustatory hallucination was uncommon, in only one patient. On neuroimaging study, 11 patients had structural lesions involving the mesial temporal structures, two exclusively involving the amygdala. Histologic diagnosis included gliosis of the mesial temporal regions in seven (58.3%) patients, neoplasm in four (33.3%) patients, and arteriovenous malformation in one patient. Postoperatively, eight patients were seizure free. Three patients had rare seizures; however, none reported residual olfactory auras. CONCLUSIONS: Olfactory auras are infrequent in TLE. In this study, mesial temporal sclerosis is the most common etiology rather than tumors. Mesial temporal structures, especially the amygdala, may play important roles in the genesis of olfactory auras.

Adolescent↗

PubMed2003

Electrocardiographic changes at the onset of epileptic seizures.

PURPOSE: We studied heart-rate (HR) changes at the transition from the preictal to the ictal state in patients with focal epilepsies to gain some insight into the mechanisms involved in the neuronal regulation of cardiovascular function. METHODS: We assessed ECG changes during 145 seizures recorded with scalp EEG in 58 patients who underwent video-EEG monitoring. Consecutive RR intervals were analyzed with a newly developed mathematical method for a total of 90 s. RESULTS: Ictal-onset tachycardia occurred in 86.9% of all seizures, whereas bradycardia was documented only in 1.4%. The incidence as well as the amount of ictal HR increase was significantly more pronounced in patients with mesial temporal lobe epilepsy (TLE) as compared with those with non-lesional TLE or extratemporal epilepsy. Moreover, right hemispheric seizures were associated with ictal-onset tachycardia. On average, ictal HR increase preceded EEG seizure onset by 13.7 s in TLE patients and 8.2 s in patients with extratemporal epilepsy. This difference was significant. Ictal HR changes could be classified according to their temporal evolution into two different patterns. These two patterns differed significantly between the temporal lobe and the extratemporal epilepsy patient group. CONCLUSIONS: Epileptic discharges directly influence areas of the central autonomic network, thus regulating HR and rhythm. Such changes occur before ictal discharges appear on surface electrodes. Our newly developed method may be of potential use for clinical applications such as automatic seizure-detection systems. Moreover, our method might help to clarify further the basic mechanisms of interactions between heart and brain.

Autonomic Nervous System↗

PubMed2002

Extracellular matrix components are altered in the hippocampus, cortex, and cerebrospinal fluid of patients with mesial temporal lobe epilepsy.

PURPOSE: This work studied the profile of glycosaminoglycans (GAGs) in the hippocampus, cortex, and cerebrospinal fluid of patients with temporal lobe epilepsy (TLE). METHODS: The GAGs were analyzed by agarose gel electrophoresis, enzymatic degradation, and enzyme-linked immunosorbent assay (ELISA). RESULTS: The hippocampus of TLE patients showed increased levels of chondroitin sulfate and hyaluronic acid against normal levels of these GAGs in the neocortex and cerebrospinal fluid (CSF). CONCLUSIONS: These results suggest that these matrix components could be involved in the pathophysiology of TLE.

Cerebral Cortex↗

PubMed1999

Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients.

We determined the interrelations of chronological age, age at seizure onset, duration of seizure disorder, cognitive functioning (IQ), scales of activities of daily living, depressive mood disorder and measures of health-related quality of life (HRQOL). Furthermore, we investigated the association of the laterality of seizure onset zone and absence/presence of hippocampal atrophy and/or sclerosis (HA/HS) with measures of HRQOL, activities of daily living (ADL) and depressive mood disorder. In the setting of pre-surgical epilepsy evaluation, a sample of 56 patients with temporal lobe epilepsy (TLE) was studied using the Bonner Skalen für Epilepsie (BPSE) and the depression inventory D-S of von Zerssen. Patients reported high levels of dependency on others and poor coping capabilities. Our data also showed specific ADL-behaviour suggesting social withdrawal and isolation. Our results indicate emotional impairment as a major problem in TLE, because 45% of our patients scored in the depressive range of the D-S depression scale. Depression score was found to be a powerful predictor of self-reported quality of life after adjusting for seizure-related variables, demographic variables and cognitive functioning (IQ). The only scale showing a significant laterality effect was ADL-home. No relationship between the dependent measures of HRQOL, ADL-social, ADL-cultural, depressive mood disorder and laterality of the epileptogenic zone or absence/presence of HA/HS was found. HRQOL and depressive mood disorder are strongly interrelated indicating that patients with depressive symptoms report lower quality of life and specific patterns of ADL. HRQOL, ADL and depressive mood disorder are largely independent of biological markers such as laterality of seizure onset zone and absence/presence of HA/HS in TLE.

Activities of Daily Living↗

PubMed2000

Disturbance of semantic processing in temporal lobe epilepsy demonstrated with scalp ERPs.

We investigated event-related potentials (N400, LPC and CNV) elicited in temporal lobe epilepsy (TLE) patients and control subjects from scalp electrodes, using a word-pair category matching paradigm. Each prime consisted of a Japanese noun (constructed from 2-4 characters of the Hiragana) followed by a Chinese character (Kanji) as the target, the latter representing one of five semantic categories. There were two equally probable target conditions: match or mismatch. Each target was preceded by a prime, either belonging to, or not belonging to, the same semantic category. The subjects were required to respond with a specified button press to the given target, according to the condition. We found RTs to be longer under the mismatch condition in both subject groups. The N400 amplitude was reduced in TLE subjects under both conditions, although LPC and CNV amplitudes showed no significant differences. These results suggest that scalp N400 is capable of demonstrating disturbance of semantic processing in TLE non-invasively.

Adult↗

PubMed2002

Neuropsychological performance in frontal lobe epilepsy.

The search for a special neuropsychological profile of frontal lobe epilepsy subjects (FLE) has so far led to inconclusive results. In this paper we compared the preoperative neuropsychological performance of FLE and temporal lobe epilepsy (TLE) subjects. We further investigated whether frontal lobe lesions of epileptogenic cause produce the same type of cognitive dysfunction as do tumours of the frontal lobe. Sixteen FLE subjects were compared to 16 TLE subjects as well as to a group of 10 subjects after the removal of frontal lobe tumors (TUM) and a healthy control group. A set of neuropsychological test measures routinely used for presurgical evaluation, an emotional conceptualization task and two associative learning tasks were administered. We found that subjects with frontal lobe damage were significantly impaired relative to controls on a wide range of cognitive functions independent of neurological cause. FLE subjects could hardly be discriminated from TLE subjects as both groups showed a similarly reduced level of neuropsychological performance. Our results demonstrate the devastating effect that frontal lobe epilepsy can have on cognitive functioning. Routinely used neuropsychological test measures lack the specificity to distinguish between frontal and temporal lobe epilepsy. Highly specialized measures are necessary to reveal differences.

Adult↗

PubMed2002

Localization of epileptogenic zone in temporal lobe epilepsy by ictal scalp EEG.

Our aim was to evaluate the ability to localize the epileptogenic zone in temporal lobe epilepsy (TLE) by ictal scalp electroencephalogram (EEG). Using simultaneous video recording, we analysed scalp EEG activity during ictal periods in 38 patients (30 patients with medial TLE (MTLE) and eight with lateral TLE (LTLE)). In 14 patients, intracranial ictal EEGs were recorded with depth electrodes, and simultaneous recordings of scalp and intracranial EEG were performed in 11 patients. Scalp EEG showed that, in all 30 patients with MTLE (71 of 72 seizures), an attenuation of background activity was observed before the appearance of ictal activity. Ictal discharges first appeared in the scalp EEG when the ictal discharges reached the lateral part of the temporal lobe on the intracranial EEG. While, in all eight patients with LTLE (25 of 25 seizures), the attenuation of background activity did not occur before the appearance of ictal activity. When the ictal discharges started in the lateral temporal lobe on intracranial EEG, ictal discharges appeared on the scalp. MTLE and LTLE could be diagnosed by the presence or absence of attenuation of background activity with clinical ictal signs before the appearance of ictal discharges.

Adolescent↗

PubMed2002

The neuropsychological and emotional consequences of living with intractable temporal lobe epilepsy: implications for clinical management.

PURPOSE: To investigate and document the neuropsychological and emotional effects of epilepsy in people with intractable temporal lobe epilepsy (TLE). METHODS: 273 patients with a diagnosis of TLE underwent a complete neuropsychological and psychological examination as a routine part of their investigation for epilepsy surgery. Neuropsychological assessment included measures of intellect, memory, language functioning, higher executive functioning, emotional well-being and the psychosocial impact of epilepsy and its treatment. RESULTS: The sample comprised 135 females and 138 males with a clearly lateralised epileptogenic focus. Patients were mildly anxious but not depressed, although many reported that epilepsy and its treatment had a marked effect on their daily lives. Current reading ability was in the average range; the mean obtained full scale IQ was 88 (low average range). Verbal memory functioning was within the borderline impaired range with visual memory functioning within the average range. Mean language performance was between the 5-10th percentile. Higher executive functioning results were in the normal range. Multiple univariate analyses were performed according to onset laterality. There were no significant differences between the groups on measures of psychological or emotional functioning. Participants with left TLE scored significantly lower than those in the right temporal group on measures of verbal intelligence, general intelligence, attention span and expressive language functioning. CONCLUSIONS: Patients with intractable epilepsy suffer significant neuropsychological difficulties in terms of their intellect, memory and language. Higher executive functioning appears unaffected. In addition, there is also evidence of emotional distress. These all impact upon their day-to-day functioning, which can be improved by the application of various psychological therapies and interventions.

Adult↗

PubMed2005

Abnormal GABAA receptors from the human epileptic hippocampal subiculum microtransplanted to Xenopus oocytes.

We studied the properties of GABAA receptors microtransplanted from the human temporal lobe epilepsy (TLE)-associated brain regions to Xenopus oocytes. Cell membranes, isolated from surgically resected brain specimens of drug-resistant TLE patients, were injected into frog oocytes, which rapidly incorporated human GABAA receptors, and any associated proteins, into their surface membrane. The receptors originating from different epileptic brain regions had a similar run-down but an affinity for GABA that was approximately 60% lower for the subiculum receptors than for receptors issuing from the hippocampus proper or the temporal lobe neocortex. Moreover, GABA currents recorded in oocytes injected with membranes from the subiculum had a more depolarized reversal potential compared with the hippocampus proper or neocortex of the same patients. Quantitative RT-PCR analysis was performed of the GABAA receptor alpha1- to alpha5-, beta1- to beta3-, gamma2- to gamma3-, and delta-subunit mRNAs. The levels of expression of the alpha3-, alpha5-, and beta1- to beta3- subunit mRNAs are significantly higher, with the exception of gamma2-subunit whose expression is lower, in subiculum compared with neocortex specimens. Our results suggest that an abnormal GABA-receptor subunit transcription in the TLE subiculum leads to the expression of GABAA receptors with a relatively low affinity. This abnormal behavior of the subiculum GABAA receptors may contribute to epileptogenesis.

Animals↗