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PubMed2003

Intractable temporal lobe epilepsy with rare spikes is less severe than with frequent spikes.

OBJECTIVE: To analyze clinical, electrophysiologic, and neuroradiologic characteristics of a group of patients with nonlesional intractable temporal lobe epilepsy (TLE) and rare or absent interictal epileptiform abnormalities (IEA). METHODS: Between 1990 and 2000, 31 patients (11 men; mean +/- SD age 34.3 +/- 11.7 years) with nonlesional intractable TLE were consecutively selected on the basis of the absence or paucity of IEA (<1/h) on serial scalp EEG recording; these were defined as "oligospikers." The clinical and laboratory characteristics of oligospikers were compared with those of a group of 27 age-matched control subjects (10 men; mean +/- SD age 38.5 +/- 11 years), randomly selected from a pool of patients with nonlesional TLE with frequent IEA. RESULTS: Oligospikers showed a later age at seizure onset (mean +/- SD 19.1 +/- 14.4 versus 10.2 +/- 7.4 years; p = 0.004), lower monthly frequency of complex partial seizures (median 6 versus 12; p = 0.035), lower incidence of secondarily generalized tonic-clonic seizures (10 versus 81%; p < 0.001), and no status epilepticus (0 versus 22%) than control subjects. Also, hippocampal atrophy (HA) was less commonly found in oligospikers (55 versus 96%; p = 0.001). However, there were no differences between the two groups in the frequency of family history of epilepsy, risk factors, febrile convulsions, and type of medication. Twenty-three (74%) oligospikers and 25 (93%) control patients underwent either a selective amygdalohippocampectomy or corticoamygdalohippocampectomy. Excellent surgical outcome (Engel's Class Ia) was found in 14 of 23 (61%) oligospikers and 17 of 25 (67%) control patients. CONCLUSIONS: This study identified a subgroup of patients with nonlesional intractable TLE with no or few IEA. Oligospikers have a later age at seizure onset, less frequent and less severe seizures, besides a lower incidence of HA. The similarity of etiologic factors compared with patients with frequent IEA suggests that the rarity of spikes could reflect a disease not really distinct but less severe, even though still intractable and incapacitating enough to consider surgery. In spite of the absence or paucity of IEA, oligospikers have excellent surgical outcome.

Adult↗

PubMed2004

EKG abnormalities in children and adolescents with symptomatic temporal lobe epilepsy.

BACKGROUND: Changes in cardiac rate and rhythm are often found in adult patients with temporal lobe epilepsy (TLE) and could be involved in the pathogenesis of sudden unexplained death (SUDEP). However, little is known about heart rate (HR) variability in pediatric patients with TLE. OBJECTIVES: To investigate ictal and peri-ictal HR abnormalities in children and adolescents with medically refractory symptomatic TLE and to determine the influence of focus localization and laterality. METHODS: Patients younger than 18 years, with drug-resistant unilateral symptomatic TLE and presenting with at least one habitual complex partial seizure (CPS) during presurgical noninvasive video-EEG monitoring, were enrolled. Synchronous single-channel EKG recordings were analyzed during the preictal, ictal, and postictal stages. RESULTS: Twenty patients fulfilled the inclusion criteria. Seventy-two temporal lobe seizures (TLSs) were analyzed. Ictal tachycardia was found in 71 TLSs (98%), whereas ictal bradycardia was not observed. During preictal stages, tachycardia occurred in 20 seizures and mild bradycardia in 3. In 44 seizures (62%), tachycardia was still present >60 seconds after EEG seizure termination. Cluster analysis revealed significant differences in HR evolution depending on location and side of seizure onset: Early and high HR increase was primarily associated with right mesial TLSs. CONCLUSIONS: Cardiovascular dysregulation is common during temporal lobe CPSs in children. These results confirm a right hemispheric lateralization of sympathetic cardiac control.

Adolescent↗

PubMed2005

Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy.

BACKGROUND: Increased levels of glutamate have been reported in the epileptogenic hippocampus of patients with temporal lobe epilepsy (TLE). This sustained increase, which may contribute to the initiation and propagation of seizure activity, indicates impaired clearance of glutamate released by neurons. Glutamate is predominantly cleared by glial cells through the excitatory amino acid transporter 2 (EAAT2) and its subsequent conversion to glutamine by the glial enzyme glutamine synthetase (GS). METHODS: The authors examined the hippocampal distribution of GS, EAAT2, and glial fibrillary acidic protein (GFAP) by immunohistochemistry in TLE patients with (HS group) and without hippocampal sclerosis (non-HS group), and in autopsy controls. In hippocampal homogenates the authors measured relative protein amounts by immunoblotting and GS enzyme activity. RESULTS: In the autopsy control and non-HS group GS immunoreactivity (IR) was predominantly found in glia in the neuropil of the subiculum, of the pyramidal cell layer of all CA fields, and in the supragranular layer of the dentate gyrus. In the HS group, GS and EAAT2 IR were markedly reduced in subfields showing neuron loss (CA1 and CA4), whereas GFAP IR was increased. The reduction in GS IR in the HS group was confirmed by immunoblotting and paralleled by decreased GS enzyme activity. CONCLUSIONS: Glial glutamine synthetase is downregulated in the hippocampal sclerosis (HS) hippocampus of temporal lobe epilepsy (TLE) patients in areas with severe neuron loss. This downregulation appears to be pathology-related, rather than seizure-related, and may be part of the mechanism underlying impaired glutamate clearance found in the hippocampus of TLE patients with HS.

Adult↗

PubMed1982

Interictal psychopathology in patients with ictal fear: a quantitative investigation.

We assessed the hypothesis that psychopathology is overrepresented in patients with temporal lobe epilepsy (TLE) who experience ictal fear. Eleven such patients were matched with two control groups: patients who had TLE without ictal fear and patients who had generalized epilepsy. On several MMPI scales, the TLE-ictal fear group scored significantly higher than the two control groups, which did not differ significantly from each other. Furthermore, the TLE-ictal fear group had more MMPI clinical scales that were pathologically elevated, had significantly more patients with histories of admission to psychiatric hospitals, and had more MMPI profiles that were psychotic than either of the control groups.

Adult↗

PubMed1993

In vivo cerebral metabolism and central benzodiazepine-receptor binding in temporal lobe epilepsy.

Positron emission tomography measured interictal cerebral glucose metabolism with [18F]fluorodeoxyglucose and central benzodiazepine-receptor binding with [11C]flumazenil in 10 mesial temporal lobe epilepsy (TLE) patients and in normal subjects. Eight TLE patients had mesial temporal, lateral temporal, and thalamic hypometabolism ipsilateral to EEG ictal onsets, with additional extratemporal hypometabolism in four. One had unilateral anterior mesial temporal hypometabolism only, and one had normal metabolism. Each patient had decreased benzodiazepine-receptor binding in the ipsilateral anterior mesial temporal region, without neocortical changes. Thus, interictal metabolic dysfunction is variable and usually extensive in TLE, whereas decreased central benzodiazepine-receptor density is more restricted to mesial temporal areas. Metabolic patterns in TLE may reflect diaschisis, while benzodiazepine-receptor changes may reflect localized neuronal and synaptic loss that is specific to the epileptogenic zone. [11C]Flumazenil imaging may be useful in presurgical evaluation of refractory complex partial seizures.

Adult↗

PubMed1998

Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis.

OBJECTIVE: One hypothesis proposes that a pre-existing alteration of medial temporal lobe structures contributes to febrile convulsions and subsequent hippocampal sclerosis (HS) in patients with temporal lobe epilepsy (TLE) and antecedent febrile convulsions. It is possible that such a structural alteration does not always lead to convulsions and may also be present in clinically unaffected relatives. METHODS: We tested this hypothesis by MRI investigation of 23 members of two families, of whom 13 had experienced febrile convulsions and 10 had not. One member of each family with febrile convulsions subsequently developed TLE. We compared the right/left ratios of hippocampal volumes (RHV) with 23 age- and sex-matched controls. Additionally, two independent raters assessed hippocampal signal intensity and pattern in T2- and fluid-attenuated inversion recovery images. RESULTS: Both TLE patients showed left HS. All subjects with febrile convulsions who did not develop epilepsy and six clinically unaffected relatives also showed asymmetric RHV (>3 standard deviation) but a normal hippocampal signal intensity. In all of these subjects, the left hippocampus was smaller. Visual inspection of these smaller hippocampi revealed blurred internal pattern or flat hippocampal bodies or both in one family and smaller hippocampal heads in the other. The pattern of HS in TLE patients showed a structural correlation with the abnormalities seen in their relatives. One subject with febrile convulsions had additional subcortical heterotopias. CONCLUSION: These findings suggest a subtle, pre-existing hippocampal malformation that may facilitate febrile convulsions and contribute to the development of subsequent HS.

Adolescent↗

PubMed1998

Epilepsy diagnosis and localization in patients with antecedent childhood febrile convulsions.

PURPOSE: A history of febrile convulsions (FC) is often obtained in patients presenting for surgical treatment of temporal lobe epilepsy (TLE), but it is not clear that preferential temporal localization of epilepsy is associated with antecedent FC. METHODS: We prospectively inquired about FC and their characteristics in all patients presenting to an epilepsy clinic through a patient questionnaire and interview. We studied the incidence of antecedent childhood febrile convulsions in relation to epilepsy diagnosis. RESULTS: FC were reported by 133 of 1005 study patients (13.2%). TLE was more likely to be preceded by FC (78/310, 25.2%) than extratemporal epilepsy (ETE) (12/216, 5.6%) (p < 0.000001) or generalized epilepsy (GE) (16/146, 11.0%) (p < 0.001). Patients with GE were more likely than patients with TLE to have had simple FC (p < 0.00005). Prolonged duration was the most common FC complex feature in TLE patients. CONCLUSIONS: We demonstrated a preferential association of FC with temporal lobe foci and a weaker association between FC and GE. FC does not appear to be a clear risk factor for ETE.

Adolescent↗

PubMed1998

Proton magnetic resonance spectroscopy in MRI-negative temporal lobe epilepsy.

OBJECTIVE: To determine the 1H MRS findings in patients with intractable temporal lobe epilepsy (TLE) who had no detectable abnormality on either qualitative or quantitative MRI. BACKGROUND: Previous work has indicated that approximately 20% of patients with TLE remain MRI negative after extensive qualitative and quantitative investigation. Single-voxel 1H MRS provides a means of identifying potentially diffuse disease. METHODS: Seven patients with intractable TLE, normal routine MRI, normal hippocampal volumes, and normal hippocampal and amygdala quantitative T2 values underwent single-voxel 1H MRS of the medial temporal lobes. The results are compared with those from 13 control subjects and 15 patients with evidence of hippocampal sclerosis (HS). RESULTS: The ratio N-acetylaspartate/(choline-creatine + phosphocreatine) was abnormally low in five of the seven MRI-negative patients. In two of these patients, the ratios were low bilaterally. The observed MRS ratios in the MRI-negative group with abnormal EEG were similar to those from temporal lobes ipsilateral to HS, suggesting the presence of widespread or diffuse disease of a similar degree in both groups. CONCLUSIONS: These results demonstrate that MRS can provide evidence of temporal lobe abnormalities in TLE patients who show no abnormality on extensive MRI investigation.

Adult↗

PubMed1998

Side of seizure focus predicts left medial temporal lobe activation during verbal encoding.

OBJECTIVE: Functional MRI (FMRI) was used to investigate the effect of medial temporal lobe (MTL) pathology on activation of language encoding areas in patients with temporal lobe epilepsy (TLE). METHODS: Whole-brain FMRI was obtained. Twenty-eight patients with either left TLE (LTLE) or right TLE (RTLE) performed a semantic decision task alternating with an auditory perceptual task. RESULTS: Activation of language areas in the frontal and parietal lobes was similar in both groups, with no group differences in the total number of active voxels. However, the RTLE group showed much stronger activation of the left MTL, including the hippocampus, parahippocampal gyrus, and collateral sulcus, than did the LTLE group. CONCLUSIONS: Activation of the left MTL during semantic encoding discriminates patients with RTLE and LTLE. This FMRI technique may potentially be of use in determining memory lateralization and for predicting the side of seizure focus in TLE.

Adult↗

PubMed1998

Is the underlying cause of epilepsy a major prognostic factor for recurrence?

BACKGROUND: We investigated the prognostic value of the type of epilepsies and epileptic syndromes for seizure recurrence. In patients with partial epilepsy, we focused on the prognostic value of any structural brain abnormality and of the location of the epileptogenic region. METHODS: A total of 2,200 adult outpatients were included in a hospital-based observational survey, with a follow-up of 1 to 7 years. Twenty-two percent of the patients exhibited generalized epilepsy, 62% partial epilepsy, and 16% undetermined epilepsy. RESULTS: Seizure control (>1 year without seizure) was achieved in 82% of patients who had idiopathic generalized epilepsy, 35% of those with symptomatic partial epilepsy, 45% of those with cryptogenic partial epilepsy, and 11% of those with partial epilepsy associated with hippocampal sclerosis (HS). Temporal lobe epilepsy (TLE) was the most refractory partial epilepsy, with only 20% of such patients remaining seizure free, compared with 36% of extra-TLE patients. In partial epilepsy, HS, cerebral dysgenesis, and dual pathology (HS and another lesion) were associated with a low rate of seizure-free patients (11%, 24%, and 3%, respectively). No significant difference in seizure control was found between patients with extra-TLE and those with TLE and no HS. CONCLUSIONS: In adults, partial epilepsy is more difficult to treat than idiopathic generalized epilepsy. In patients who have partial epilepsy, the location of the epileptogenic zone does not seem to be a determining factor. Brain abnormalities--especially HS, either alone or associated with another lesion--are a major prognostic factor.

Adolescent↗

PubMed1999

Coexistence of temporal lobe and idiopathic generalized epilepsies.

OBJECTIVE: To assess the interrelation of idiopathic generalized epilepsy (IGE) and temporal lobe epilepsy (TLE) when they coexist in the same patient. METHODS: The authors reviewed the electroclinical features of 350 consecutive patients who had temporal resection between 1975 and 1997 at the Maudsley and King's College Hospitals, London. RESULTS: Two patients had the unusual combination of TLE and IGE (0.57%). In the first, the clinical onset of juvenile myoclonic epilepsy followed the surgical resolution of his partial seizures but had been heralded for at least 5 years by subclinical spontaneous and photically induced generalized spike-wave discharges. In the second, TLE and juvenile absence epilepsy had a long parallel course before surgery. After surgery he had no further partial seizures. CONCLUSION: These cases suggest that when an idiopathic absence or myoclonic syndrome manifests in a patient with symptomatic TLE, the phenotype may not be a merged syndrome. Rather, the two conditions can retain their inherent electroclinical profile, responsiveness to treatment, and prognosis.

Adult↗

PubMed2001

Postictal stability of proton magnetic resonance spectroscopy imaging (1H-MRSI) ratios in temporal lobe epilepsy.

Interictal proton (1H) MRS is increasingly used for seizure lateralization in patients with temporal lobe epilepsy (TLE). Studies reporting postictal 1H-MRS metabolite changes in patients with TLE are few and contradictory. The authors prospectively performed interictal and postictal proton magnetic resonance spectroscopy imaging (1H-MRSI) studies in seven patients with TLE. The authors found no consistent changes in metabolite peak area ratios between studies, suggesting that 1H-MRS ratios remain stable between interictal and postictal state in TLE.

Adolescent↗

PubMed2000

Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription.

The Runt related transcription factors RUNX (AML/CBF(alpha)/PEBP2(alpha)) are key regulators of hematopoiesis and osteogenesis. Using co-transfection experiments with four natural promoters, including those of the osteocalcin (OC), multi drug resistance (MDR), Rous Sarcoma Virus long terminal repeat (LTR), and bone sialoprotein (BSP) genes, we show that each of these promoters responds differently to the forced expression of RUNX proteins. However, the three RUNX subtypes (i.e. AML1, AML2, and AML3) regulate each promoter in a similar manner. Although the OC promoter is activated in a C terminus dependent manner, the MDR, LTR and BSP promoters are repressed by three distinct mechanisms, either independent of or involving the AML C terminus, or requiring only the conserved C-terminal pentapeptide VWRPY. Using yeast two hybrid assays we find that the C terminus of AML1 interacts with a Groucho/TLE/R-esp repressor protein. Co-expression assays reveal that TLE proteins repress AML dependent activation of OC gene transcription. Western and northern blot analyses suggest that TLE expression is regulated reciprocally with the levels of OC gene expression during osteoblast differentiation. Digital immunofluorescence microscopy results show that TLE1 and TLE2 are both associated with the nuclear matrix, and that a significant subset of each colocalizes with AML transcription factors. This co-localization of TLE and AML proteins is lost upon removing the C terminus of AML family members. Our findings indicate that suppression of AML-dependent gene activation by TLE proteins involves functional interactions with the C terminus of AML at the nuclear matrix in situ. Our data are consistent with the concept that the C termini of AML proteins support activation or repression of cell-type specific genes depending on the regulatory organization of the target promoter and subnuclear localization.

Animals↗

PubMed2000

[Familial partial epilepsies].

OBJECTIVE: To investigate the clinical and genetic characteristics of familial partial epilepsies. METHOD: Family history of seizures was questioned in all patients followed in our epilepsy clinics, from October 1997 to December 1998. Those with positive family history were further investigated and detailed pedigrees were obtained. All possibly affected individuals available underwent clinical evaluation. Seizures and epilepsy syndromes were classified according to the ILAE recommendations. Whenever possible, EEG and MRI were performed. RESULTS: Positive family history was identified in 32 unrelated patients. A total of 213 possibly affected individuals were identified, 161 of whom have been evaluated. The number of affected subjects per family ranged from two to 23. Temporal lobe epilepsy (TLE) was identified in 22 families (68%), frontal lobe epilepsy in one family (3%), partial epilepsy with centrotemporal spikes in five families (15%), and other benign partial epilepsies of childhood in four families (12%). Most of the affected individuals in the TLE families (69%) had clinical and/or EEG characteristics of typical TLE. However, the severity of epilepsy was variable, with 76% of patients with spontaneous seizure remission or good control with medication and 24% with refractory seizures, including 7 patients that underwent surgical treatment. In the other 10 families, we identified 39 possibly affected subjects, 23 of whom were evaluated. All had good seizure control (with or without medication) except for one patient with frontal lobe epilepsy. Pedigree analysis suggested autosomal dominant inheritance with incomplete penetrance in all families. CONCLUSION: Family history of seizures is frequent among patients with partial epilepsies. The majority of our families had TLE and its expression was not different from that observed in sporadic cases. The identification of genes involved in partial epilepsies may be usefull in classification of syndromes, to stablish prognosis and optimal treatment.

Adolescent↗

PubMed2005

Statistical voxel-wise analysis of ictal SPECT reveals pattern of abnormal perfusion in patients with temporal lobe epilepsy.

OBJECTIVE: To investigate the pattern of perfusion abnormalities in ictal and interictal brain perfusion SPECT images (BSI) from patients with temporal lobe epilepsy (TLE). METHOD: It was acquired interictal and ictal BSI from 24 patients with refractory TLE. BSIs were analyzed by visual inspection and statistical parametric mapping (SPM2). Statistical analysis compared the patients group to a control group of 50 volunteers. The images from patients with left-TLE were left-right flipped. RESULTS: It was not observed significant perfusional differences in interictal scans with SPM. Ictal BSI in SPM analysis revealed hyperperfusion within ipsilateral temporal lobe (epileptogenic focus) and also contralateral parieto-occipital region, ipsilateral posterior cingulate gyrus, occipital lobes and ipsilateral basal ganglia. Ictal BSI also showed areas of hypoperfusion. CONCLUSION: In a group analysis of ictal BSI of patients with TLE, voxel-wise analysis detects a network of distant regions of perfusional alteration which may play active role in seizure genesis and propagation.

Adolescent↗

PubMed2001

A visual learning and memory test for preoperative evaluation of patients with temporal lobe epilepsy.

We used a modified version of the visual DCS (mDCS) test to study patterns of learning, free recall, and recognition capacity in patients with temporal lobe epilepsy (TLE) (N = 24) and controls (N = 38). The patients were under consideration for epilepsy surgery. The mDCS differentiated left from right TLE patients in all aspects of visuospatial learning and delayed recall. The mDCS revealed lower performance for TLE patients as compared with controls. The present results indicate that the mDCS may be a preoperative tool to differentiate left from right TLE.

Adult↗

PubMed2001

Hemispheric specialization in emotion: attention, arousal, and EEG activation in unilateral temporal lobe epilepsy.

To investigate the neural processing of emotion in right and left temporal lobe epilepsy (TLE), we monitored EEG during neutral and emotionally positive and negative auditory stimulation. Left TLE patients displayed increased right lateralization and a negative emotional stimulus rating bias, while right TLE patients did not. This EEG arousal and negative affect may reflect deactivated inhibition of the right hemisphere, symptomatically expressed as arousal and anxiety. Failure to increase lateralization to emotional stimuli in right TLE may reflect compromised emotional attention/arousal centers in the right hemisphere. Results support a two-dimensional theory of the neural processing of emotion.

Acoustic Stimulation↗

PubMed1996

Cognitive performances in newly referred patients with temporal lobe epilepsy: comparison with normal subjects in basal condition and after treatment with controlled-release carbamazepine.

In order to verify whether the performance of patients with temporal lobe epilepsy (TLE) were different from those of the normal controls in various cognitive tasks, we conducted a neuropsychological study in the two groups, excluding the presence of other confounding factors in the group of TLE patients (newly referred, previously untreated, without cerebral lesions at neuroimaging, with low recurrence of seizures). In basal condition, no significant difference was found between the nine healthy controls and the eight TLE patients. The second aim of the study was to investigate the effect of the first administration of 400 mg controlled-release carbamazepine (CBZ-CR). The drug caused a significant decrease in verbal memory (short and long-term) in TLE patients, whereas, in the control group, the first administration of CBZ-CR caused only a less significant impairment of long-term verbal-memory. Finally, the cognitive effects of CBZ-CR were assessed after one month of therapy, only in the group of patients. Our data suggest that: 1) differences between patients and controls in basal conditions are not relevant, once the influence of seizures, of treatment and of anatomical lesions has been ruled out. In other words, our patients did not perform differently from controls simply because they had become epileptic 2) also in the controlled-release preparation, adverse effects of CBZ on cognitive function are minimal and limited to the beginning of treatment.

Adult↗