Familial temporal lobe epilepsy: a clinically heterogeneous syndrome

We describe the clinical characteristics of a group of patients with familial temporal lobe epilepsy (TLE) in 11 kindreds with 36 affected individuals identified and investigated at the Montreal Neurological Hospital. Seizure types were simple partial (n = 20), complex partial (n = 29), and rare generalized tonic-clonic. Simple and complex partial seizures were infrequent or well controlled by anticonvulsant medication in 17 of 29 patients (59%) and without optimal response to medical therapy in 12 of 29 patients (41%). Pedigree analysis suggested autosomal dominant inheritance with incomplete penetrance. The syndrome of familial TLE has heterogeneous clinical manifestations and is not always benign.     

Relationship between anatomic lesions of the temporal lobe and temporal lobe epilepsy

A structural lesion of the brain is a frequent finding in intractable partial epileptic patients. We analyse anatomo-electro-clinical characteristics of 58 patients in which MR showed a lesion inside the temporal lobe. They are 29 males and 29 females with a mean age at surgery of 23.5 +/- 10.7 years (2.6-45.9). The mean epilepsy duration is of 13.4 +/- 8 years (1.3-35.5), with a mean seizure frequency of 28.7 +/- 43.6 per month, with a great inter-individual variability (from 3 per month to 15 a day). The minimum follow-up is 3.5 years. A video-EEG monitoring was performed in 21 cases, while a stereo-EEG investigation was judged mandatory in 26. On the basis of anatomo-electro-clinical correlations and of the results of presurgical investigations, the epileptogenic area was proved to be temporal in 49 cases, temporal but controlateral to the lesion in 1, and at least bilobar in 8 patients.     

Stereotaxic surgery of temporal lobe epilepsy

Forty patients with temporal epilepsy were operated on with a stereotaxic technique. Eleven patients had a unilateral localization of the epileptic focus, and in 29 bitemporal foci were diagnosed. In evaluating the results of the treatment the dynamics of the epileptic fits, the peculiarities of changes in the mental status, and the degree of social adaptation were taken into consideration. A postoperative improvement was achieved in 73% of the patients with monotemporal lesions, while in those with bitemporal epilepsy and distinct persistent mental disorders the state was improved in 44% of the cases. Indications for the choice of the zone of destruction depending on the clinical peculiarities of the lesion are presented.     

Outcome after temporal lobectomy in bilateral temporal lobe epilepsy

We determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure-free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure-free outcome. Seven of 10 seizure-free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure-free outcome included location of scalp interictal spikes, degree of seizure-onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full-scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.     

Neuropsychological outcome following anterior temporal lobectomy in patients with and without the syndrome of mesial temporal lobe epilepsy.

The nature, pattern, and degree of neuropsychological change following anterior temporal lobectomy (ATL) were examined as a function of the presence or absence of the syndrome of mesial temporal lobe epilepsy (MTLE). Fifty-four patients exhibited the syndrome of MTLE, while 34 patients were without the syndrome (non-MTLE). The test-retest performance of a group of 40 epilepsy patients who did not undergo surgery was used to derive regression based estimates of test-retest change. Overall, the MTLE group did not show significant cognitive decline following ATL. In contrast, the left non-MTLE group showed significant declines on verbal memory, confrontation naming, and verbal conceptual ability. Further, verbal memory was the most substantial area of decline, and was independent of seizure outcome. Clinical and theoretical implications of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Functional MRI lateralization of memory in temporal lobe epilepsy

OBJECTIVE: To determine the feasibility of using functional magnetic resonance imaging (fMRI) to detect asymmetries in the lateralization of memory activation in patients with temporal lobe epilepsy (TLE). BACKGROUND: Assessment of mesial temporal lobe function is a critical aspect of the preoperative evaluation for epilepsy surgery, both for predicting postoperative memory deficits and for seizure lateralization. fMRI offers several potential advantages over the current gold standard, intracarotid amobarbital testing (IAT). fMRI has already been successfully applied to language lateralization in TLE. METHODS: fMRI was carried out in eight normal subjects and 10 consecutively recruited patients with TLE undergoing preoperative evaluation for epilepsy surgery. A complex visual scene encoding task known to activate mesial temporal structures was used during fMRI. Asymmetry ratios for mesial temporal activation were calculated, using regions of interest defined in normals. Patient findings were compared with the results of IAT performed as part of routine clinical evaluation. RESULTS: Task activation was nearly symmetric in normal subjects, whereas in patients with TLE, significant asymmetries were observed. In all nine patients in whom the IAT result was interpretable, memory asymmetry by fMRI concurred with the findings of IAT including two patients with paradoxical IAT memory lateralization ipsilateral to seizure focus. CONCLUSIONS: fMRI can be used to detect asymmetries in memory activation in patients with TLE. Because fMRI studies are noninvasive and provide excellent spatial resolution for functional activation, these preliminary results suggest a promising role for fMRI in improving the preoperative evaluation for epilepsy surgery.     

Quantitative analysis of interictal behavior in temporal lobe epilepsy

Patients with unilateral temporal epileptic foci were contrasted with normal subjects and patients with neuromuscular disorders in the evaluation of specific psychosocial aspects of behavior. Eighteen traits were assessed in equivalent questionnaires completed by both subjects and observers. The epileptic patients self-reported a distinctive profile of humorless sobriety, dependence, and obsessionalism; raters discriminated temporal lobe epileptics on the basis of circumstantiality, philosophical interests, and anger. The right temporal epileptic displayed emotional tendencies in contrast to ideational traits of left temporal epileptic. Right temporal epileptics exhibited "denial," while left temporal epileptics demonstrated a "catastrophic" overemphasis of dissocial behavior. The results support the hypotheses that sensory-affective associations are established within the temporal lobes, and that, in man, there exists a hemispheric asymmetry in the expression of affect.     

Cortical and hippocampal volume deficits in temporal lobe epilepsy

PURPOSE: To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE). METHODS: Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA). RESULTS: As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe. CONCLUSIONS: Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.     

Sex differences in patients with mesial temporal lobe epilepsy

Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.     

Amygdala damage in experimental and human temporal lobe epilepsy

The amygdala complex is one component of the temporal lobe that may be damaged unilaterally or bilaterally in children and adults with temporal lobe epilepsy (TLE) or following status epilepticus. Most MR (magnetic resonance) imaging studies of epileptic patients have shown that volume reduction of the amygdala ranges from 10-30%. In the human amygdala, neuronal loss and gliosis have been reported in the lateral and basal nuclei. Studies in rats have more specifically identified the amygdaloid regions that are sensitive to status epilepticus-induced neuronal damage. These areas include the medial division of the lateral nucleus, the parvicellular division of the basal nucleus, the accessory basal nucleus, the posterior cortical nucleus, and portions of the anterior cortical and medial nuclei. Otherwise, other amygdala nuclei, such as the magnocellular and intermediate divisions of the basal nucleus and the central nucleus, remain relatively well preserved. Amygdala kindling studies in rats have shown that the density of a subpopulation of GABAergic inhibitory neurons that also contain somatostatin may be reduced even after a low number of generalized seizures. While analyses of histological sections and MR images indicate that in approximately 10% of TLE patients, seizure-induced damage is isolated to the amygdala, more often amygdala damage is combined with damage to the hippocampus and/or other brain areas. Moreover, recent data from rodents and nonhuman primates suggest that structural and functional alterations caused by seizure activity originating in the amygdala are not limited to the amygdala itself, but may also affect other temporal lobe structures. The information gathered so far on damage to the amygdala in epilepsy or after status epilepticus suggests that local alterations in inhibitory circuitries may contribute to a lowered seizure threshold and greater excitability within the amygdala. Furthermore, damage to select nuclei in the amygdala may predict impairment of performance in behavioral tasks that depend on the integrity of the amygdaloid circuits.     

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.     

Preserved monitoring and control processes in temporal lobe epilepsy.

Objective: The aim of this study was to assess an aspect of metamemory never examined before in patients with temporal lobe epilepsy (TLE): the ability to upgrade the accuracy of one's memory predictions after study. Method: Four lists of different levels of difficulty and relatedness were presented to 15 TLE patients and 15 control participants, who were asked to predict their subsequent recall both before and after studying each list. Results: The results showed clear impairment in recall in TLE patients. However, both TLE patients and controls showed an improvement in accuracy in their poststudy predictions compared with their prestudy predictions, showing that both groups were able to upgrade their metamemory predictions. Unexpectedly, prediction accuracy was overall higher in TLE patients than in controls. Moreover, study time was allocated in both groups taking into account the characteristics of the list. Conclusion: These results confirm and extend findings of Howard et al. (2010) of intact metamemory in TLE patients, and provide further support to the dissociation between memory and metamemory in this clinical population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.     

Memory and intelligence in lateralized temporal lobe epilepsy and schizophrenia

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.     

Single photon emission computed tomography-EEG relations in temporal lobe epilepsy

The role of single photon emission computed tomography (SPECT) as an independent confirmation test in presurgical evaluation of medically intractable temporal lobe epilepsy has not been critically investigated. Because spreading ictal discharges may cause a concomitant increase of cerebral blood flow in remote cerebral regions, a careful analysis of peri-injection EEG patterns and their relation to ictal SPECT may be important in evaluating the reliability of ictal SPECT. Both interictal and ictal EEG and SPECT were reviewed in 19 patients with temporal lobe epilepsy who achieved a successful seizure outcome after surgery. Patients were divided into unitemporal and bitemporal groups according to the lateralization of interictal epileptiform discharges (IED). Ictal EEG features were classified into lateralized and nonlateralized groups. The concordance between SPECT and EEG lateralizations was examined in each patient and correlated to the documented epileptogenic temporal lobe. Interictal SPECT correctly lateralized in eight of nine patients with unitemporal IED and in five of 10 patients with bitemporal IED. Ictal SPECT was highly concordant with the peri-injection ictal EEG but correctly lateralized the epileptogenic region in only 11 of 19 patients. When both pre- and postinjection EEG epochs lateralized ipsilaterally, all ictal SPECT images showed concordant lateralization. If pre- and postinjection EEG epochs were either different in lateralization or nonlateralization, ictal SPECT images often showed complex patterns of cerebral perfusion with a high incidence of false lateralization. Interictal SPECT was more sensitive and reliable in patients with unitemporal IED than in patients with bitemporal IEDs. Ictal SPECT was closely related with peri-injection EEG epochs but with frequent false lateralization. The role of ictal SPECT as an independent confirmation test in presurgical evaluation should be reappraised.     

Microdysgenesis in mesial temporal lobe epilepsy: a clinicopathological study

The interrelationship of mesial temporal lobe epilepsy (MTLE), hippocampal sclerosis, and febrile convulsions still remains an enigma. Additional microscopical cortical dysplasia or microdysgenesis has been suggested as pre-existent susceptibility factor rendering the affected brain vulnerable to the development of MTLE after initial precipitating injuries such as febrile convulsions. Twenty-four MTLE cases with histopathologically definite hippocampal sclerosis were examined for clearly defined features of microdysgenesis and further signs of neocortical dysplasia. Although unequivocal signs of dysplasia were absent, 29.2% of cases showed cortical neuronal clustering, 25.0% showed perivascular clustering, and 20.8% showed increased white matter neurons. The features of microdysgenesis studied here were not linked with each other and were not related to initial precipitating injuries, positive family history, or any other clinical parameter. Their suggested fundamental role as dysplastic factor within development of hippocampal sclerosis and MTLE is not confirmed.     

Interictal spiking increases with sleep depth in temporal lobe epilepsy

PURPOSE: To test the hypothesis that deepening sleep activates focal interictal epileptiform discharges (IEDs), we performed EEG-polysomnography in 21 subjects with medically refractory temporal lobe epilepsy. METHODS: At the time of study, subjects were seizure-free for > or =24 h and were taking stable doses of antiepileptic medications (AEDs). Sleep depth was measured by log delta power (LDP). Visual sleep scoring and visual detection of IEDs also were performed. Logistic-regression analyses of IED occurrence in relation to LDP were carried out for two groups of subjects, nine with frequent IEDs (group 1) and 12 with rare IEDs (group 2). Results: The LDP differentiated visually scored non-rapid eye movement (NREM) sleep stages (p = 0.0001). The IEDs were most frequent in NREM stages 3/4 and least frequent in REM sleep. Within NREM sleep, in both groups, IEDs were more frequent at higher levels of LDP (p < 0.05). In group 1, after accounting for the level of LDP, IEDs were more frequent (a) on the ascending limb of LDP and with more rapid increases in LDP (p = 0.007), (b) in NREM than in REM sleep (p = 0.002), and (c) closer to sleep onset (p < 0.0001). Fewer than 1% of IEDs occurred within 10 s of an EEG arousal. CONCLUSIONS: Processes underlying the deepening of NREM sleep, including progressive hyperpolarization in thalamocortical projection neurons, may contribute to IED activation in partial epilepsy. Time from sleep onset and NREM versus REM sleep also influence IED occurrence.     

Object naming and semantic knowledge in temporal lobe epilepsy.

Object-naming impairment is common among temporal lobe epilepsy (TLE) patients, but other aspects of semantic memory have received limited attention in this population. This study examined object-naming ability and depth of semantic knowledge in healthy controls (n?=?29) and patients with early onset TLE (n?=?21). After administration of the Boston Naming Test (BNT), the authors asked participants to provide detailed definitions of 6 BNT objects. The TLE group demonstrated a significant deficit relative to controls in both object-naming ability and semantic knowledge for the target objects, even after controlling for IQ. In a multiple regression analysis that included other neuropsychological test scores as independent variables, the semantic knowledge score was the only significant predictor of patients' object-naming performance. Thus, at the group level, early onset TLE patients have a semantic knowledge deficit that contributes to dysnomia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)