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PubMed2004

Acquired dendritic channelopathy in temporal lobe epilepsy.

Inherited channelopathies are at the origin of many neurological disorders. Here we report a form of channelopathy that is acquired in experimental temporal lobe epilepsy (TLE), the most common form of epilepsy in adults. The excitability of CA1 pyramidal neuron dendrites was increased in TLE because of decreased availability of A-type potassium ion channels due to transcriptional (loss of channels) and posttranslational (increased channel phosphorylation by extracellular signal-regulated kinase) mechanisms. Kinase inhibition partly reversed dendritic excitability to control levels. Such acquired channelopathy is likely to amplify neuronal activity and may contribute to the initiation and/or propagation of seizures in TLE.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Dormancy of inhibitory interneurons in a model of temporal lobe epilepsy.

In humans temporal lobe epilepsy (TLE) is characterized by recurrent seizures, neuronal hyperexcitability, and selective loss of certain neuronal populations in the hippocampus. Animal models of the condition indicate that a diminution of inhibition mediated by gamma-aminobutyric acid (GABA) accounts for the altered function, and it has been hypothesized that the diminution arises because GABAergic basket interneurons are "dormant" as a result of their being disconnected from excitatory inputs. In hippocampal slices, inhibitory postsynaptic potentials (IPSPs) were elicited in CA1 pyramidal cells by activation of basket cells; responses from an animal model of TLE were compared to those from control tissue. IPSPs evoked indirectly by activation of terminals that then excited basket cells were reduced in the epileptic tissue, whereas IPSPs evoked by direct activation of basket cells, when excitatory neurotransmission was blocked, were not different from controls. These results provide support for the "dormant basket cell" hypothesis and have implications for the pathophysiology and treatment of human TLE.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1992

Viscosity and social cohesion in temporal lobe epilepsy.

Clinical case reports suggest that viscosity, the behavioural tendency to talk repetitively and circumstantially about a restricted range of topics, is common in patients with temporal lobe epilepsy (TLE). Such patients are also reported to exhibit heightened levels of social cohesion, the tendency to become interpersonally "clingy". This "sticky" interpersonal style may be particularly common in TLE patients with a left sided temporal lobe seizure focus. To test this hypothesis, self-report and observer rating scales were developed to assess both viscosity and social cohesion. Subjects consisted of patients with right, left, or bilateral temporal lobe seizure foci, absence or primary generalised tonic-clonic seizures, psychiatric controls (panic disorder patients), and normal controls. Elevations on the viscosity scale were observed primarily in TLE patients with left or bilateral seizure foci. Viscosity scores also correlated with seizure duration and left handedness. No group differences were observed on the social cohesion scale. These findings are consistent with the hypothesis that viscosity results from subtle interictal language disturbances, although other pathogenetic mechanisms are discussed.

Anomia↗

PubMed1988

Nonrefractory temporal lobe epilepsy: 1.5-T MR imaging.

Thirty-one patients with temporal lobe epilepsy (TLE) of mild to moderate severity, well controlled by pharmacotherapy (nonrefractory TLE), and with negative findings at computed tomography, were studied with magnetic resonance (MR) imaging at 1.5 T. Examination disclosed significant findings in 16 patients: mesial temporal abnormalities (n = 9), basitemporal abnormalities (n = 2), and alterations in frontoparietal white matter (n = 5). Coronal views and sequences with a 120-msec echo time (TE) depicted lesions in 16 patients; axial views depicted lesions in only nine of 16 patients; sequences with a 35-msec TE depicted lesions in only ten. These results underline the importance of screening with MR imaging in nonrefractory TLE patients and suggest that the MR imaging sequence of choice is a thin-section, coronal, T2-weighted sequence.

Adolescent↗

PubMed1997

Differential epilepsy-associated alterations in postsynaptic GABA(A) receptor function in dentate granule and CA1 neurons.

Alterations in GABAergic function associated with the development of temporal lobe epilepsy (TLE) were examined with the use of patch-clamp recording techniques in dentate granule (DG) and CA1 neurons acutely isolated from control and spontaneously epileptic rats in which TLE was elicited by pilocarpine injection 3-17 wk before use. The maximal efficacy of gamma-aminobutyric acid (GABA) in activating whole cell GABA currents increased significantly in epileptic DG neurons relative to controls. This efficacy increase was due to a 78% enhancement in the functional capacitance-normalized GABA(A) receptor (GABA(A)R) current density in epileptic DG neurons. Increased DG GABA(A)R current density was not accompanied by alterations in GABA potency (EC50). However, the maximal sensitivity of DG GABA-evoked currents to blockade by zinc increased 190% in epileptic neurons. Augmentation of epileptic DG neuron GABA-evoked currents by the broad-spectrum anticonvulsant benzodiazepine clonazepam (100 nM) was enhanced 114% relative to controls, whereas augmentation by the benzodiazepine, (BZ1)-selective agonist zolpidem (100 nM) was decreased by 66%. In contrast to DG neurons, maximal efficacy of GABA in activating GABA currents decreased in epileptic CA1 neurons relative to controls, due to a 52% decrease in functional capacitance-normalized GABA(A)R current density. This altered efficacy of GABA was accompanied by an increased GABA potency (GABA EC50 was 35.8 and 24.5 microM in control and epileptic neurons, respectively). Sensitivity of GABA-evoked currents to blockade by zinc was unchanged in epileptic CA1 neurons, whereas clonazepam (100 nM) augmentation of CA1 GABA-evoked currents decreased 81% relative to controls. These regionally distinct epilepsy-associated modifications in hippocampal GABAergic function may be due to discrete structural alterations in postsynaptic GABA(A)Rs accompanying epileptogenesis, could be therapeutically important, and undoubtedly could contribute to the enhanced limbic excitability underlying TLE.

Animals↗

PubMed1997

Interneurons in area CA1 stratum radiatum and stratum oriens remain functionally connected to excitatory synaptic input in chronically epileptic animals.

Past work has demonstrated a reduction of stimulus-evoked inhibitory input to hippocampal CA1 pyramidal cells in chronic models of temporal lobe epilepsy (TLE). It has been postulated that this reduction in inhibition results from impaired excitation of inhibitory interneurons. In this report, we evaluate the connectivity of area CA1 interneurons to their excitatory afferents in hippocampal-parahippocampal slices obtained from a rat model of chronic TLE. Rats were made chronically epileptic by a period of continuous electrical stimulation of the hippocampus, which establishes an acute condition of self-sustained limbic status epilepticus (SSLSE). This period of SSLSE is followed by a development of chronic recurrent spontaneous limbic seizures that are associated with chronic neuropathological changes reminiscent of those encountered in human TLE. Under visual control, whole cell patch-clamp recordings of interneurons and pyramidal cells were obtained in area CA1 of slices taken from adult, chronically epileptic post-SSLSE rats. Neurons were activated by means of electrodes positioned in stratum radiatum. Intrinsic membrane properties, including resting membrane potential, action potential (AP) threshold, AP half-height width, and membrane impedance, were unchanged in interneurons from chronically epileptic (post-SSLSE) tissue compared with control tissue. Single stimuli delivered to stratum radiatum evoked depolarizing excitatory postsynaptic potentials and APs in interneurons, whereas paired-pulse stimulation evoked facilitation of the postsynaptic current (PSC) in both control and post-SSLSE tissue. No differences between interneurons in control versus post-SSLSE tissue could be found with respect to the mean stimulus intensity or mean stimulus duration needed to evoke an AP. A multiple linear regression analysis over a range of stimulus intensities demonstrated that a greater number of APs could be evoked in interneurons in post-SSLSE tissue compared with control tissue. Spontaneous PSCs were observed in area CA1 interneurons in both control and post-SSLSE tissue and were markedly attenuated by glutamatergic antagonists. In conclusion, our data suggest that stimulus-evoked and spontaneous excitatory synaptic input to area CA1 interneurons remains functional in an animal model of chronic temporal lobe epilepsy. These findings suggest, therefore, that the apparent decrease of polysynaptic inhibitory PSPs in CA1 pyramidal cells in epileptic tissue is not due to a deficit in excitatory transmission from Schaffer collaterals to interneurons in stratum radiatum and straum oriens.

Animals↗

PubMed1999

Development of a model of status epilepticus in pigtailed macaque infant monkeys.

Seizures, particularly multiple episodes and/or status epilepticus (SE) are prevalent in pediatric patients. Pediatric SE is associated with brain changes that have been hypothesized to contribute to the onset of temporal lobe epilepsy (TLE). In order to gain insight into the effects of seizures on the immature brain and the risk for later TLE, we have developed a model of limbic SE in the pigtailed macaque monkey. In separate studies, bicuculline methiodide or a bicuculline 'cocktail' was infused into three regions of the brain (area tempestas, hippocampus, entorhinal cortex) to induce seizures. Measures included MRI, electrophysiology, behavior and morphology. Our results suggest that monkey models of SE may provide useful tools for understanding the effects of prolonged seizures during infancy and the origins of TLE in humans.

Animals↗

PubMedDate not supplied

Mitochondrial tRNA(Cys) mutation A5823G in a patient with motor neuron disease and temporal lobe epilepsy.

We discovered a new homoplasmic mutation in the mitochondrial cysteine tRNA of a 60-year-old Caucasian male suffering from asymmetrical pure lower motor neuron disease (MND) and temporal lobe epilepsy (TLE). Furthermore, titrations with Amytal, an inhibitor of NADH:CoQ oxidoreductase, revealed mild mitochondrial dysfunction in skeletal muscle tissue, which was described in patients with MND in an earlier report. The mutation was undetectable in 155 Caucasian controls of both sexes, in 40 MND patients and in 13 individuals suffering from TLE. It was, however, detected in a heteroplasmic state in the patient's mother, who did not suffer from a neurological disorder. Since this rare mutation affected a nonconserved base position and was not observed in MND or TLE materials, its relation to disease remains unclear.

Blotting, Southern↗

PubMed1999

Usefulness of the dipole tracing method with a scalp-skull-brain head model: relationship between the epileptic focus and equivalent current dipole locations.

PURPOSE: We examined whether the dipole tracing (DT) method with a realistic three-shell head model and inhomogeneous electric conductivity is useful to estimate the epileptic focus from interictal spikes. METHOD: This study included 17 temporal lobe epilepsy (TLE) cases, classified into three types as type A (unilateral), type B (intermediate) and type C (bilateral) and 5 extratemporal epilepsy (XTLE) cases. The epileptic areas were determined by noninvasive and/or invasive examinations. Selected interictal spikes were analyzed and the calculated equivalent current dipoles (ECDs) of dipolarity greater than 0.98 were superimposed over the realistic head model in each patient. We evaluated the ECD concentration within and around the epileptic area. RESULTS: In TLE cases, types A showed better ECD concentration (87%) within the epileptic area than other types (type B: 68%; type C: 74%). XTLE exhibited variable ECD distribution within and around the epileptic area. CONCLUSION: The DT method with a realistic head model and inhomogeneous electric conductivity can be useful to estimate the epileptic area from interictal spikes, especially in unilateral TLE cases.

Action Potentials↗

PubMed2005

To BDNF or not to BDNF: that is the epileptic hippocampus.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has drawn much attention as a potential therapeutic target for temporal lobe epilepsy (TLE). TLE seizures are produced by synchronized hyperactivity of neuron populations due to the disruption of a balance between excitatory and inhibitory synaptic transmissions. In epileptogenesis-related brain areas, including the hippocampus, BDNF is up-regulated in the course of the development of epilepsy and induces a collapse of balanced excitation and inhibition, eventually exerting its epileptogenic effects. On the other hand, several reports demonstrate that intrahippocampal infusion of BDNF can attenuate (or retard) the development of epilepsy. This antiepileptogenic effect seems to be mediated mainly by an increase in the expression of neuropeptide Y. These contrasting effects of BDNF have prevented us from concluding whether inhibition or enhancement of BDNF signaling finally achieves the prevention of TLE. To address this question, it is essential to evaluate how BDNF changes its influences depending on conditions, for example, cell specificity, neural networks, and expression timing and loci. In this article, the authors review BDNF-induced acute and long-lasting changes seen in epileptic circuits from the anatomical and functional points of view.

Animals↗

PubMed1994

P300 event-related potentials in epileptic children.

To evaluate the cognitive function of epileptic children, we examined P300 in 50 patients, 32 with idiopathic generalized epilepsy (IGE) and 18 with temporal lobe epilepsy (TLE), and 39 normal children. There were significant negative correlations between age and P300 latencies at Pz and Cz in normal controls. For data analysis, we used the age-corrected latency, which was calculated as the interval between the actual and predicted P300 latencies. The predicted latency was calculated with the regression equation as the relationship between P300 latency and age in normal controls. The age-corrected P300 latencies recorded from Pz and Cz were significantly longer in patients with IGE (41.5 +/- 13.1, 42.0 +/- 12.5) than in control subjects (0 +/- 7.5, 0 +/- 7.9). There were no significant differences in age-corrected P300 latencies between patients with TLE (21.2 +/- 17.6, 31.5 +/- 17.0) and controls, or IGE and TLE. Recently, it was considered that the mesencephalic reticular formation and thalamus may play major roles in the genesis of generalized epilepsy, so we speculate that dysfunction of these systems may contribute to the prolongation of P300 in children with idiopathic generalized epilepsy.

Adolescent↗

PubMed1997

EEG investigation of temporal lobe epilepsy.

We report the results of the study assessing the role of electroencephalogram (EEG) in the evaluation of patients with temporal lobe epilepsy (TLE). A prospective interictal EEG study was performed in 80 patients with TLE, and the results were compared with those of neuroimaging magnetic resonance imaging (MRI) and computed tomography (CT). All patients had interictal scalp-recorded electroencephalographic monitoring with a full array of electrodes placed according to the International 10-20 Placement System, CT and MRI. Scalp EEG had a success rate of 70% in TLE patients, this rate was 50% for MRI and 15% for CT. Epileptiform EEG abnormalities were unilateral in 25 (31%) and bilateral in 31 (39%) patients. In 56% of patients with unilateral interictal activity and 97% of patients with bilateral interictal activity, epileptiform activity was localized at the temporal electrodes. The wave morphology which we most frequently saw in our study was the sharp, sharp-slow wave or spike, or spike-wave. A correlation was observed between the focal MRI-CT abnormalities and the EEG findings. We found abnormal imaging incidence in patients with unilateral EEG findings to be significantly greater than in patients with bilateral EEG findings (chi 2 = 4.62, p = .032). EEG showed abnormality in 28 (70%) of 40 patients whose neuroimaging (NI) tests were found abnormal and also did in 70% of 40 patients whose NI tests were normal. In our study EEG has remained as the most efficient test in the localization of an epileptogenic focus.

Adult↗

PubMed2002

Global affective memory for faces in patients with temporal lobe epilepsy.

Eighteen (9 left, 9 right) epileptic patients with unilateral temporal lobe epilepsy (TLE) and 20 control participants were evaluated. Participants were instructed to make global affective judgments of likeability in a face memory task or to make neutral piecemeal judgments of nose size during the encoding phase of the task. A main effect of better memory after using a global affective versus a neutral piecemeal encoding strategy was found. Patients with right sided abnormality performed more poorly in the global affective encoding condition than patients with left-sided abnormality or than the control participants. No differences were seen among groups for the neutral piecemeal condition. Further, unlike the left TLE patients and the control participants, the right TLE patients did not show better performance when using the global affective encoding strategy over the neutral piecemeal strategy. This is discussed in relation to the literature suggesting an important role for the right hemisphere in global affective processing and memory, as well as the literature indicating an important role for the amygdala in affective memory.

Adolescent↗

PubMed2002

Asymmetric termination of secondarily generalized tonic-clonic seizures in temporal lobe epilepsy.

In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.

Adult↗

PubMed2003

The pathological basis of temporal lobe epilepsy in childhood.

OBJECTIVE: To characterize the pathologic findings of temporal lobe epilepsy (TLE) in children undergoing temporal lobectomy for refractory seizures and to correlate these findings with clinical presentation. METHODS: The authors reviewed the charts of all children who underwent anterior temporal lobectomy for refractory TLE from 1979 through 1999. A new neuropathologic analysis was performed blinded to clinical features and outcome. RESULTS: Twenty-two children met inclusion criteria. Mean age at onset of epilepsy was 3 years, 7 months (range 1 month to 10 years). Mean age at surgery was 10 years, 11 months (range 1 to 18 years). All patients had complex partial seizures, 48% with secondary generalization. Most had daily seizures. Auras were reported in 45% of patients. Post-resection follow-up averaged 5 years, 2 months (range 2 to 19 years). Seizure-free status was achieved in 41% of patients, and 14% had residual auras only. The most frequent neuropathologic abnormalities were cortical dysplasia (CD) of the temporal neocortex (14 of 22) and mesial temporal sclerosis (MTS) (12 of the 15 children with available hippocampal tissue). These two findings coexisted in seven children. MTS was associated with extra-hippocampal pathology in 8 of 12 (67%) of the cases. CONCLUSIONS: MTS occurs frequently in association with CD in this population of children. The high incidence of dual pathology could explain the early age of seizure onset and high seizure frequency rate observed. TLE in childhood may constitute a different entity than in adults, from both the clinical and neuropathologic perspectives.

Adolescent↗

PubMed2003

Naming and recognizing famous faces in temporal lobe epilepsy.

OBJECTIVE: To assess naming and recognition of faces of familiar famous people in patients with epilepsy before and after anterior temporal lobectomy (ATL). METHODS: Color photographs of famous people were presented for naming and description to 63 patients with temporal lobe epilepsy (TLE) either before or after ATL and to 10 healthy age- and education-matched controls. RESULTS: Spontaneous naming of photographed famous people was impaired in all patient groups, but was most abnormal in patients who had undergone left ATL. When allowed to demonstrate knowledge of the famous faces through verbal descriptions, rather than naming, patients with left TLE, left ATL, and right TLE improved to normal levels, but patients with right ATL were still impaired, suggesting a new deficit in identifying famous faces. Naming of famous people was related to naming of other common objects, verbal memory, and perceptual discrimination of faces. Recognition of the identity of pictured famous people was more related to visuospatial perception and memory. CONCLUSIONS: Lesions in anterior regions of the right temporal lobe impair recognition of the identities of familiar faces, as well as the learning of new faces. Lesions in the left temporal lobe, especially in anterior regions, disrupt access to the names of known people, but do not affect recognition of the identities of famous faces. Results are consistent with the hypothesized role of lateralized anterior temporal lobe structures in facial recognition and naming of unique entities.

Adult↗

PubMed2004

Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy.

OBJECTIVE: To evaluate testicular function in men with epilepsy treated with different antiepileptic drugs (AED) vs no drugs. METHODS: Two hundred men with epilepsy (mean age 36 years) were investigated. Inclusion criteria included one or no AED, no co-medication, and no endocrine co-morbidity. Findings were compared with those from 105 healthy men (mean age 33.9 years). Luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), free testosterone (free T), and inhibin B were measured. RESULTS: One hundred seventy-eight men had focal epilepsy (117 of these had temporal lobe epilepsy [TLE]) and 22 idiopathic generalized epilepsy (IGE). Thirty-three men were not on AED; 124 men received enzyme-inducing AED. Free T was lowered in all patient subgroups, and the T/LH ratio was lowered in all groups except patients with IGE and patients receiving valproate (VPA). T was lower in patients with temporal than extratemporal focal epilepsy. Compared with TLE patients on carbamazepine (CBZ), patients treated with VPA had higher total T and lower LH values, resulting in a significantly lower T/LH ratio with CBZ. CONCLUSIONS: Epilepsy, especially TLE, adversely affects testicular endocrine function. CBZ may increase the negative effects of epilepsy on serum levels of reproductive hormones.

Adult↗

PubMed2005

Racial disparities in the use of surgical treatment for intractable temporal lobe epilepsy.

OBJECTIVE: To compare the use of surgical treatment for epilepsy among different ethnic and racial groups with surgically remediable temporal lobe epilepsy (TLE). METHODS: The authors used multiple logistic regression analysis to model the use of anterior temporal lobectomy in a cross-sectional study of video-EEG monitoring discharge data among residents of Alabama and surrounding states discharged from the University of Alabama at Birmingham Hospital between July 1998 and January 2003 with a primary diagnosis of TLE. RESULTS: Of 432 patients diagnosed with TLE, 130 had evidence of mesial temporal sclerosis on MRI studies. Seventy patients underwent surgery; African Americans were less likely than non-Hispanic whites to undergo surgical treatment (odds ratio, 0.3; 95% CI, 0.2 to 0.8). After potential demographic (age, education, and sex), socioeconomic, medical insurance coverage, and clinical confounders (bitemporal seizure onset) were controlled, African Americans had a 60% less chance to receive surgery than non-Hispanic whites. CONCLUSIONS: There are disparities in the use of surgical treatment for temporal lobe epilepsy. Race appears to be an influential factor related to such disparities.

Adult↗