Frontal lobe function in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is typically associated with long-term memory dysfunction. The frontal lobes support high-level cognition comprising executive skills and working memory that is vital for daily life functioning. Deficits in these functions have been increasingly reported in TLE. Evidence from both the neuropsychological and neuroimaging literature suggests both executive function and working memory are compromised in the presence of TLE. In relation to executive impairment, particular focus has been paid to set shifting as measured by the Wisconsin Card Sorting Task. Other discrete executive functions such as decision-making and theory of mind also appear vulnerable but have received little attention. With regard to working memory, the medial temporal lobe structures appear have a more critical role, but with emerging evidence of hippocampal dependent and independent processes. The relative role of underlying pathology and seizure spread is likely to have considerable bearing upon the cognitive phenotype and trajectory in TLE. The identification of the nature of frontal lobe dysfunction in TLE thus has important clinical implications for prognosis and surgical management. Longitudinal neuropsychological and neuroimaging studies assessing frontal lobe function in TLE patients pre- and postoperatively will improve our understanding further.     

Extratemporal lobe circuits in temporal lobe epilepsy

There is increasing interest in the functional anatomy of epilepsy with the goal to identify the critical nodes in the seizure circuits so that therapy can be directed at them. This goal is especially important because direct delivery of therapy, either through electrical stimulation, drug infusion, or molecular therapies such as optogenetics, has become increasingly possible. In this article, we will review the basic functional anatomy of mesial temporal lobe epilepsy and its primary subcortical connection, the medial dorsal nucleus of the thalamus. Based on its anatomical connections and known physiological interactions, we propose a key role for this thalamic nucleus that is essential for the development of seizures, and this role suggests that this region is a potential therapeutic target.This article is part of a Special Issue entitled “NEWroscience 2013”.     

Exercise-induced temporal lobe epilepsy

Although precipitation of seizures by exercise has been described, the reproducible induction of temporal lobe seizures by exercise is unusual. The authors report two patients with left temporal lobe seizures induced by exercise. In one patient the family history suggested autosomal-dominant inheritance. Prolonged hyperventilation, simple movements, and visualization of a competitive game did not produce epileptiform discharges on the interictal EEG.     

Hypersalivation in temporal lobe epilepsy

PURPOSE: We sought to determine whether hypersalivation helps lateralize seizure onset during complex partial seizures of temporal lobe origin. Several clinical signs, which help lateralize seizure onset, have been reported in temporal lobe epilepsy (TLE). Increased salivation only occasionally has been reported as a manifestation of partial epilepsy. METHODS: Of 590 consecutive patients admitted for video-EEG monitoring, either as a part of a presurgical evaluation of medically intractable epilepsy or for diagnosis and clarification of their paroxysmal symptoms, we identified 10 patients with ictal hypersalivation as a prominent manifestation of complex partial seizures. We reviewed the clinical features, scalp-sphenoidal video-EEG monitoring, intracarotid amytal (Wada) testing, hippocampal volumetric magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of these patients. RESULTS: Of the 10 patients with ictal hypersalivation, seven patients had nondominant/right TLE, and three patients had dominant/left TLE. All patients had hippocampal atrophy on volumetric MRI. Eight of the 10 patients underwent standard temporal lobectomy with amygdalohippocampectomy (six right, two left). All of the operated-on patients had a seizure-free (Engel class I) outcome, and their increased salivation resolved. Two patients, who did not undergo surgical treatment, continue to have complex partial seizures with increased salivation. CONCLUSIONS: We conclude that increased salivation as a prominent ictal finding in complex partial seizures of temporal lobe origin is more likely to be of nondominant temporal lobe origin. Further studies with larger numbers of patients are needed to replicate this finding.     

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).     

y-氨基丁酸受体与颞叶癫痫的研究进展

颞叶癫痫（TemporalLobeEpilepsy,TLE）是最常见的一种癫痫综合征,根据发病位置分为内、外侧颞叶癫痫,其中内侧颞叶癫痫（MesialTLE,MTLE）以海马硬化为主要病理改变,与海马局部中间神经元功能障碍、环路重构,胶质增生以及大脑兴奋抑制失衡有关。TLE多数呈耐药性,严重影响患者的生活质量,对TLE的研究一直是学术界的热点。近年来发现7-氨基丁酸（GABA）受体改变与TLE关系密切。GABA作为哺乳动物脑内最主要的抑制性神经递质,在大脑广泛分布。现对GABA受体与TLE相关性的研究进展作一综述。     

Medial temporal lobe atrophy in patients with refractory temporal lobe epilepsy

OBJECTIVE: The objective of this study was to assess the volumes of medial temporal lobe structures using high resolution magnetic resonance images from patients with chronic refractory medial temporal lobe epilepsy (MTLE). METHODS: We studied 30 healthy subjects, and 25 patients with drug refractory MTLE and unilateral hippocampal atrophy (HA). We used T1 magnetic resonance images with 1 mm isotropic voxels, and applied a field non-homogeneity correction and a linear stereotaxic transformation into a standard space. The structures of interest are the entorhinal cortex, perirhinal cortex, parahippocampal cortex, temporopolar cortex, hippocampus, and amygdala. Structures were identified by visual examination of the coronal, sagittal, and axial planes. The threshold of statistical significance was set to p<0.05. RESULTS: Patients with right and left MTLE showed a reduction in volume of the entorhinal (p<0.001) and perirhinal (p<0.01) cortices ipsilateral to the HA, compared with normal controls. Patients with right MTLE exhibited a significant asymmetry of all studied structures; the right hemisphere structures had smaller volume than their left side counterparts. We did not observe linear correlations between the volumes of different structures of the medial temporal lobe in patients with MTLE. CONCLUSION: Patients with refractory MTLE have damage in the temporal lobe that extends beyond the hippocampus, and affects the regions with close anatomical and functional connections to the hippocampus.     

Depression in temporal lobe epilepsy before epilepsy surgery

PURPOSE: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. RESULTS: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.     

Medial temporal lobe epilepsy: gender differences

The present study investigated the gender differences in medial temporal lobe epilepsy (MTLE) with regard to clinical history, seizure semiology, and EEG data. To avoid the influence of pathological and localisation differences, we included only MTLE patients with hippocampal sclerosis. Patients who had long term video EEG recordings with registered seizures and unilateral hippocampal sclerosis proved by high resolution MRI were included. There were 153 patients (86 women and 67 men) who met our inclusion criteria. The mean age of the patients was 33.5 years (range 16-59). The mean age at epilepsy onset was 10.8 years. Although there were more women than men, this difference was not significant (p = 0.15). We found that male patients experienced generalised seizures significantly more often, and isolated auras significantly less often than female patients. Analysing EEG data, we found that a seizure pattern lateralised to the side of the hippocampal sclerosis occurred more often in female patients. In the logistic regression analysis, we found that all three factors were associated independently with gender. Odds ratio (OR) for female gender in patients with generalised seizures was 0.44 (95% confidence interval (95% CI) 0.21 to 0.92; p<0.05). In patients with isolated auras OR for female gender was 2.1 (95% CI 1.1 to 4.2; p<0.05). OR for female gender in patients with lateralised seizure pattern was 8.8 (95% CI 1.8 to 42.7; p<0.01). Men more often had secondarily generalised tonic-clonic seizures, while women had isolated auras and lateralised EEG seizure pattern more often. Our data suggest that the seizure spread is more extended or occurs more frequently in men than in women.     

Mitochondrial involvement in temporal lobe epilepsy

Mitochondrial dysfunction has been identified as a potential cause of epileptic seizures and therapy-resistant forms of severe epilepsy. Thus, a broad variety of mutation in mitochondrial DNA or nuclear genes leading to the impairment of mitochondrial respiratory chain or of mitochondrial ATP synthesis has been associated with epileptic phenotypes. Additionally, with a variety of different methods impaired mitochondrial function has been reported for the seizure focus of patients with temporal lobe epilepsy and Ammon's horn sclerosis and of animal models of temporal lobe epilepsy. Since mitochondrial oxidative phosphorylation provides the major source of ATP in neurons and mitochondria participate in cellular Ca²⁺ homeostasis, their dysfunction strongly affects neuronal excitability and synaptic transmission, which is proposed to be highly relevant for seizure generation. Additionally, mitochondrial dysfunction is known to trigger neuronal cell death, which is a prominent feature of therapy-resistant temporal lobe epilepsy. Therefore, mitochondria have to be considered as promising targets for neuroprotective strategies in epilepsy.     

Senile plaques in temporal lobe epilepsy

Senile plaques (SP) are one of the characteristic pathological lesions of Alzheimer's disease (AD). They are also seen in the brains of some non-demented individuals as an age-related change. Identification of clinical conditions associated with these incidental SP could provide insight into AD pathogenesis. We have examined the presence of SP in lobectomy specimens (n=101) removed in the surgical treatment of temporal lobe epilepsy (TLE). SP were present in 10 specimens from epileptic patients aged 36 to 61 years and the presence of SP correlated positively with patient age. No other significant AD-related pathology was identified and no patients showed any evidence of dementia on neuropsychological testing. When compared with temporal lobe tissue from non-demented, non-epileptic autopsy controls (n=406), the density and distribution of SP was the same. The age-related incidence of SP however, was significantly greater in the epileptics. This suggests that some aspects of TLE has a positive influence on the formation of SP.Generously supported by a grant from the Alzheimer Association of Ontario     

Postictal psychosis in temporal lobe epilepsy

PURPOSE: Postictal psychosis is a well-known complication, occurring especially in patients with temporal lobe epilepsy. It usually runs a benign course. The literature on this topic is sparse, and the underlying pathogenic mechanisms are not known. METHODS: We report five patients with temporal lobe epilepsy in whom postictal psychosis developed during the course of video-EEG monitoring; they were studied with hexamethyl-propyleneamine-oxime single-photon emission computed tomography (HMPAO-SPECT) during and after the psychotic event. RESULTS: In comparison to the interictal state, all SPECT scans obtained during postictal psychosis were remarkable for bifrontal and bitemporal hyperperfusion patterns. Some studies also demonstrated unilateral left lateral frontal hyperperfusion. These cortical blood-flow patterns appeared to be distinct from those obtained during complex partial seizures. CONCLUSIONS: Our data suggest that postictal psychoses in patients with temporal lobe epilepsy are associated with hyperactivation of both temporal and frontal lobe structures. This hyperperfusion may reflect ongoing (subcortical) discharges, active inhibitory mechanisms that terminate the seizure, or simply a dysregulation of cerebral blood flow.     

Sleep disorders in temporal lobe epilepsy

The objective of this study was to evaluate sleep macrostructure and sleep disturbance in a group of 39 patients with temporal lobe epilepsy (TLE). Patients completed questionnaires to evaluate their sleep and subjective daytime sleepiness (Epworth Sleepiness Scale [ESS]) and undergone Polysomnography and Multiple Sleep Latency Test (MSLT). Daytime sleepiness was the most frequent complaint (85%), followed by wakefulness during sleep, history of seizures during sleep (75%) and initial insomnia (26%). Parasomnias (67%), obstructive sleep apneas (13%), restless legs syndrome (15%) and periodic limb movements (5%) were the most frequent sleep disorders. The most frequent changes of sleep patterns were: sleep architecture fragmentation (100%), decreased amount of REM sleep (92%) and increase in time awake after sleep onset (77%). There were significative correlations between the ESS and the MSLT (p<0,05). In conclusion, TLE patients have fragmented sleep with increased sleep stages shifts, increased number of awakenings and in time awake after sleep onset. REM sleep was decreased. Daytime sleepiness was the most frequent complaint in TLE patients.     

Number processing in temporal lobe epilepsy

BACKGROUND: Specific cognitive impairments have been found in association with mesial temporal lobe epilepsy (TLE), such as deficits in declarative memory or verbal abilities. No attention has been paid so far to possible deficits in number processing. OBJECTIVE: To investigate deficits in number processing in patients with TLE. METHODS: Numerical abilities were assessed in 28 right handed patients with medically intractable unilateral TLE and in a control group. RESULTS: No differences between patients and controls were found in analogue number processing with Arabic input, in a comparison task, or in simple addition and simple subtraction; however, there were significant group differences in tasks with verbal input, in simple division, in complex mental calculation, in a semantic knowledge task, and in conceptual tasks. Only minor differences were found between patients with right and left TLE. CONCLUSIONS: While numerical deficits may be expected in patients with left sided TLE, it is open for discussion why patients with right sided TLE also show numerical deficits.