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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.

Adolescent↗

Quantification of temporal lobe resections: a new approach.

Extent of resection in temporal lobectomy has been traditionally based on intraoperative linear measurements. The complex geometrical contour of the temporal lobe limits the precision and accuracy of such measurements, and it is often difficult to verify the extent of actual resection after surgery. The authors propose a new method of evaluating extent of resection based on a 20-compartment model of the temporal lobe. The temporal lobe is divided into five anteroposterior coronal sections in relation to the anterior and posterior borders of the mesencephalon. Each section is then divided into superior lateral, inferior lateral, basal, and medial quadrants. The resulting compartments are easily identified on postoperative magnetic resonance images obtained along the coronal plane. Resection within each compartment is noted as none (0), partial (1), or complete (2). An index of resection can then be computed for superior lateral, inferior lateral, basal, and medial quadrants and for the whole temporal lobe. Potentially, this technique can be used to evaluate surgical failures and correlate extent of resection with surgical outcome and neurologic complications. It also allows objective and semiquantitative comparison of surgical approaches practiced at different institutions.

Anthropometry↗

Pathological status of the mesial temporal lobe predicts memory outcome from left anterior temporal lobectomy.

This investigation tested the hypothesis that the degree of impairment to memory function caused by an anterior temporal lobectomy (ATL) is inversely related to the pathological status of the resected hippocampus. Specifically, the greatest risk to postoperative memory function should be to patients with no or minimal hippocampal sclerosis, i.e., those with a functional hippocampus. Forty patients who underwent a partial resection of the left (n = 21) or right (n = 19) anterior temporal lobe were administered tests of immediate and delayed verbal and figural memory, both preoperatively and 6 months postoperatively. The degree of postoperative impairment in memory function was then investigated as a function of the degree of hippocampal sclerosis, as determined by a standardized procedure. For a left ATL, an absence or mild degree of hippocampal sclerosis was associated with significantly greater postoperative impairment of both verbal and figural memory, compared with patients with moderate or marked sclerosis. No statistically significant relationship was noted for patients who underwent a right ATL, but the findings were in the same direction for five of six memory measures. It may be possible to predict and avoid surgically induced impairment of memory function among patients who undergo left ATL through the use of preoperative hippocampal volumetric magnetic resonance imaging. Better clinical tests of right hippocampal function are needed to predict the outcome for patients who undergo a right ATL.

Adult↗

Experimental models of temporal lobe epilepsy: new insights from the study of kindling and synaptic reorganization.

Temporal lobe epilepsy is a common localization-related epileptic syndrome characterized by complex partial seizures, ictal and interictal epileptic discharges arising from limbic structures of the temporal lobe, and association with hippocampal sclerosis. Temporal lobe epilepsy may follow perinatal injury and febrile convulsions, may be progressive, and frequently becomes refractory to standard antiepileptic therapy. The neurobiology that underlies these features of temporal lobe epilepsy is not known. Recent studies in experimental models have provided new insights that may help clarify the relationship of seizures, hippocampal sclerosis, and temporal lobe epilepsy. Observations from the study of the hippocampus with kainic acid-induced lesions, the kindling model, and other experimental models of epilepsy have demonstrated that seizures induce structural and electrophysiologic alterations in hippocampal pathways that may lead to increased excitability and could play a role in the development and progression of temporal lobe epilepsy. These alterations include mossy fiber synaptic reorganization, induction of NMDA-mediated synaptic transmission, and progressive hippocampal neuronal loss induced by brief kindled seizures. Some of the structural alterations induced by kindling have also been observed in the human epileptic temporal lobe, raising the possibility that mechanisms operative in kindling may play a role in the pathogenesis of hippocampal sclerosis and in the syndrome of human temporal lobe epilepsy.

Animals↗

Unitemporal vs bitemporal hypometabolism in mesial temporal lobe epilepsy.

BACKGROUND: Patients with mesial temporal lobe epilepsy (TLE) often show bilateral temporal hypometabolism (BTH), but the nature of this finding has not been well established. OBJECTIVE: To compare the clinical characteristics between unitemporal hypometabolism (UTH) and BTH patients in mesial TLE. DESIGN: Cross-sectional study. SETTING: Epilepsy center at university hospital in Seoul, Korea. PATIENTS: We enrolled 95 patients with mesial TLE, 87 of whom had subsequently undergone surgery. Seizures, interictal and ictal electroencephalography (EEG), brain magnetic resonance imaging, Wada test, and neuropsychological test results were reviewed. (18)F-fluorodeoxyglucose positron emission tomography scans were interpreted visually. Patients were divided into 2 groups: UTH and BTH. RESULTS: There were 59 UTH patients and 36 BTH patients. Semiologic analysis showed that UTH patients had higher frequencies of aura and unilateral dystonic posturing, whereas BTH patients had higher frequencies of a nonlateralized bilateral ictal EEG pattern and bilateral interictal spikes. Moreover, BTH patients had more frequent symmetric Wada memory scores and white matter changes in the bilateral temporal lobes on brain magnetic resonance imaging than UTH patients. All UTH patients with bilateral TLE on scalp EEG showed unilateral seizure onset on intracranial EEG. CONCLUSIONS: The characteristic clinical findings of mesial TLE with BTH were a more frequent nonlateralized ictal EEG pattern, bitemporal interictal spikes, symmetric Wada memory score, and the anterior temporal white matter changes, and less frequent aura and unilateral dystonic posturing. Surgical outcomes were similar and good in both groups, although surgery could not be performed in 8 BTH patients (22%).

Adult↗

Memory impairment in temporal lobe epilepsy: the role of entorhinal lesions.

Temporal lobe epilepsy (TLE) patients are frequently afflicted with deficits in spatial and other forms of declarative memory. This impairment is likely associated with the medial temporal lobe, which suffers widespread damage in the disease. Physiological and lesion studies, as well as examinations of the complex connectivity of the medial temporal lobe in animals and humans, have identified the entorhinal cortex (EC) as a key structure in the function and dysfunction of this brain region. Lesions in EC layer III, which normally provides monosynaptic input to area CA1 of the hippocampus, frequently occur in TLE and may be causally related to the memory impairments seen in the disease. Lesions that are initially largely restricted to EC layer III can be produced in rats by focal intra-entorhinal injections of 'indirect excitotoxins' such as aminooxyacetic acid or gamma-acetylenic GABA. These animals eventually show more extensive neurodegeneration in temporal lobe structures and, after a latent period, exhibit spontaneously recurring seizure activity. These progressive features, which may mimic events that occur in TLE, provide new opportunities to explore the role of the EC in memory deficits associated with TLE. These animals will also be useful for evaluating new treatment strategies that focus on the prevention of pathological events in the EC.

Animals↗

Quantifying interictal metabolic activity in human temporal lobe epilepsy.

The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.

Brain↗

Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis.

PURPOSE: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLE-no. METHODS: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 +/- 9.7 years), 17 TLE-no (mean age, 35.6 +/- 11.1 years), and 30 healthy controls (mean age, 30.3 +/- 11.1 years). RESULTS: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi- and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS. CONCLUSIONS: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi- and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself.

Adult↗

Spared discrimination and impaired reversal eyeblink conditioning in patients with temporal lobe amnesia.

The effect of medial temporal lobe damage on a 2-tone delay discrimination and reversal paradigm was examined in human classical eyeblink conditioning. Eight medial temporal lobe amnesic patients and their demographically matched controls were compared. Amnesic patients were able to distinguish between 2 tones during the initial discrimination phase of the experiment almost as well as control participants. Amnesic patients were not able to reverse the previously acquired 2-tone discrimination. In contrast, the control participants showed improved discrimination performance after the reversal of the tones. These findings support the hypothesis that the hippocampus and associated temporal lobe regions play a role in eyeblink conditioning that becomes essential in more complex versions of the task, such as the reversal of an acquired 2-tone discrimination.

Adult↗

Mesial temporal lobe epilepsy: what have we learned?

Mesial temporal lobe epilepsy is the most common form of human epilepsy, and its pathophysiological substrate is usually hippocampal sclerosis, the most common epileptogenic lesion encountered in patients with epilepsy. The disabling seizures associated with mesial temporal lobe epilepsy are typically resistant to antiepileptic drugs but can be abolished in most patients by surgical treatment. Anteromesial temporal resection, therefore, is the most common surgical procedure performed to treat epilepsy, and stereotactically implanted intracerebral electrodes are required in some patients to localize the epileptogenic region. This clinical setting provides a large number of patients for invasive in vivo research with microelectrode and microdialysis techniques and in vitro research following surgical resection on a single epileptic disorder. Consequently, much has now been learned about the fundamental neuronal mechanisms underlying the epileptogenic properties of the human hippocampus in mesial temporal lobe epilepsy. Parallel reiterative studies in patients and animal models of this disorder indicate that enhanced inhibition, in addition to enhanced excitation, underlies the appearance of hypersynchronous neuronal discharges responsible for generating spontaneous seizures. Recent studies have elucidated what may be unique electrophysiological markers of epileptogenicity, which could have valuable diagnostic utility. Although basic research on mesial temporal lobe epilepsy may ultimately suggest novel approaches to treatment and prevention, attention must also be given to maximizing the application of available effective treatments. In particular, the safety and efficacy of surgical therapy has greatly improved in recent years, yet this alternative treatment remains seriously underutilized worldwide. An appropriate increase in referral of patients with this surgically remediable syndrome to epilepsy centers will not only relieve a great many patients of their disabling seizures and reduce the burden of epilepsy but will also provide increased opportunities for invasive research that could ultimately result in even more effective therapies or cures.

Animals↗

Olfactory dysfunction in schizophrenia and temporal lobe epilepsy.

BACKGROUND: Schizophrenia and mesial temporal lobe epilepsy (TLE) represent two common brain disorders that share dysfunction of temporo-limbic neural substrates. OBJECTIVE: We evaluated whether patients with schizophrenia exhibited olfactory performance more similar to right or left temporal lobe epilepsy patients. METHODS: Odor identification ability and detection threshold sensitivity were measured in 40 patients with schizophrenia, 14 patients with right- and 18 patients with left-temporal lobe epilepsy (TLE) patients, and 25 healthy controls. Odor identification was assessed with the University of Pennsylvania Smell Identification Test (UPSIT) and odor detection threshold sensitivity with a single-staircase procedure using the stimulant phenyl ethyl alcohol (PEA). RESULTS: Relative to controls, only patients with schizophrenia and right TLE exhibited significant impairment in UPSIT performance. Left TLE patients and controls performed comparably on the UPSIT. Detection threshold sensitivity to PEA did not differ significantly among the four groups. CONCLUSIONS: These data suggest a greater reliance of olfactory processing on right hemisphere structures and are also consistent with recent neuroimaging studies that have implicated aberrant processing of olfactory information in right hemispheric brain regions in schizophrenia.

Adult↗

Seizures accelerate forgetting in patients with left-sided temporal lobe epilepsy.

Ten patients with refractory temporal lobe epilepsy performed a word-position association learning task every 24 hours during video EEG monitoring. On 55 occasions recall performance was tested 30 minutes and 24 hours after the initial learning phase. Patients with left- but not right-sided temporal lobe epilepsy exhibited impaired retention of word position if a seizure had occurred during the preceding 24-hour interval. Seizures may impair the consolidation of memory in patients with left-sided temporal lobe epilepsy beyond the chronic memory deficits caused by the underlying pathology.

Adult↗

Reduced sensitivity of the N400 and late positive component to semantic congruity and word repetition in left temporal lobe epilepsy.

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% "congruous" (category exemplars) and 50% "incongruous" (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from approximately 10-140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

Adult↗

Limbic P3 potentials, seizure localization, and surgical pathology in temporal lobe epilepsy.

Limbic P3 event-related potentials were recorded from mesial temporal electrodes implanted for presurgical investigation in 70 patients with intractable focal seizures. In 46 (81%) of 57 patients with unilateral temporal lobe epilepsy, the limbic P3 potential was absent or rudimentary ipsilateral to the seizure focus and a robust P3 potential was always elicited from the nonepileptogenic temporal lobe. Bilateral P3 potentials were recorded in 6 patients (10%) with unilateral temporal lobe epilepsy. In the remaining 5 patients in the group with unilateral temporal lobe epilepsy, results showed P3 bilaterally absent (2 patients), P3 present in a unilateral investigation (1 patient), P3 absent contralateral to the seizure focus (1 patient), and technically unsatisfactory recordings (1 patient). Bilaterally absent P3 potentials were noted in 2 patients with bilateral temporal lobe epilepsy. In 6 patients with technically adequate P3 studies and extratemporal seizures, bilaterally present P3 potentials were noted. Sensitivity and specificity of P3 absence as a predictor of an epileptogenic temporal lobe were 87% and 95%, respectively. Tissue specimens of the hippocampus were available in 22 patients (43%). Thirteen hippocampi showed sclerosis, all of which were associated with unilaterally absent P3 potentials. Nine hippocampi were normal (5 patients with the P3 absent, 4 with P3 present). Sensitivity and specificity of an absent limbic P3 as a function of hippocampal pathological findings were 100% and 44%, respectively. Absent limbic P3 potentials in temporal lobe epilepsy thus indicate structural or functional hippocampal abnormality and may add important information in presurgical evaluation with depth electrodes of patients who have temporal lobe epilepsy.

Adolescent↗

A study of the relationship between the seizure focus and 1H-MRS in temporal lobe epilepsy and frontal lobe epilepsy.

Several studies of temporal lobe epilepsy (TLE) patients have investigated the relationship between the seizure focus and 1H magnetic resonance spectroscopy (1H-MRS). There have also been a few reports in other types of partial epilepsy. We examined the relationship between the seizure focus and the reduction in N-acetylaspartate: creatine (NAA : Cr) ratio using 1H-MRS in both TLE and frontal lobe epilepsy (FLE) patients. We studied 21 patients with unilateral TLE and seven patients with unilateral FLE. We used a 1.5 Tesla magnetic resonance unit (Signa Horizon; General Electric). Approximately 15 x 15 x 20 mm3 voxel of interest (VOI) was placed over the anterior portion of the bilateral hippocampus in the TLE patients, and the anterodorsal position of bilateral frontal lobe in the FLE patients. The seizure focus was identified by interictal scalp electro-encephalogram (EEG). In the TLE patients the NAA : Cr ratios were reduced in the seizure focus, while in the FLE patients they were not always reduced in the seizure focus. In the TLE patients the coincidence rate between the seizure focus and the reduction in the NAA:Cr ratio was 90% (19 of 21 patients), while in the FLE patients the coincidence rate was only 57% (four of seven patients).

Adult↗

Recall and recognition memory in patients with focal frontal, temporal lobe and diencephalic lesions.

Patients with frontal, temporal lobe, or diencephalic lesions were compared with healthy controls on measures of recall and recognition memory for word lists. Exposure times were titrated to match recognition memory scores 30 s after the end of word-list presentation as closely as possible. Using this technique, we failed to find a disproportionate impairment in recall memory in either the frontal lobe lesion patients or in the amnesic (temporal lobe and diencephalic) patients, compared with healthy controls. Consistent with this finding, performance on these tasks showed highly significant correlations with anterograde memory quotients (despite the titration procedure), but not with executive/frontal function tasks. On the other hand, the frontal lobe lesion group showed disproportionate benefit in the recall of semantically categorised words, compared with unrelated words. This may indicate an impairment in retrieval or access, compared with the amnesic (temporal lobe and diencephalic) patients, and/or an inability to organise their learning of unrelated words spontaneously, compared with healthy controls.

Adult↗

Magnetic resonance spectroscopy in temporal lobe epilepsy.

We used proton magnetic resonance spectroscopy (1H MRS) to investigate the temporal lobes of 25 patients with temporal lobe epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine + phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the temporal lobes ipsilateral to the seizure focus showed a mean reduction of 22% in the NAA signal, with a 15% increase in the Cr signal and a 25% increase in the Cho signal. There were smaller effects in the contralateral temporal lobes. These spectral abnormalities may reflect neuronal loss or damage, together with reactive astrocytosis. The NAA/Cho+Cr ratio was abnormally low in 88% of the patients, 40% showing bilateral effects. On the basis of the NAA/Cho+Cr ratio, we correctly achieved lateralization in 15 cases, with three incorrect. Two of the incorrect lateralizations also had imaging abnormalities on the contralateral side, and the other had severe bilateral abnormalities on MRS. We conclude that 1H MRS provides useful information in the preoperative investigation of patients with temporal lobe epilepsy, contributing to lateralization and detecting bilateral abnormalities.

Adolescent↗

Orbito-frontal epilepsy masquerading as temporal lobe epilepsy-a case report.

Temporal lobectomy fails to control seizures in a considerable percentage of patients who do not have hippocampal sclerosis. One theoretical reason for failure of surgery is that some of these patients may in fact have extratemporal epilepsy. We present a 28-year-old woman with clinical and scalp electroencephalogram (EEG) evidence of right temporal lobe epilepsy (TLE) supported by functional imaging with interictal positron emission tomography (PET) and ictal single-photon emission computerized tomography (SPECT). An invasive EEG monitoring was prompted by the discovery of a small right orbito-frontal lesion on MRI. Monitoring documented seizure onset at the lesion, with rapid right temporal involvement. The patient was almost seizure-free after a lesionectomy. The index of suspicion of orbito-frontal epilepsy should be high in patients with apparent TLE when the scalp EEG and neuroimaging data are not congruent, or if temporal lobe pathology cannot be identified on structural imaging.

Adult↗