Interictal rhythmical midline theta differentiates frontal from temporal lobe epilepsies

Purpose:   We evaluated the role of interictal rhythmical midline theta (RMT) in the identification of frontal lobe epilepsy (FLE) and its differentiation from temporal lobe epilepsy (TLE) and nonepileptic controls.
Methods:   We included 162 individuals in the study: 54 FLE patients, 54 TLE patients, and 54 nonepileptic controls. Continuous electroencephalographic (EEG)-video monitoring was performed in all individuals. Interictal RMT was included only if it occurred during definite awake states. RMT associated with drowsiness or mental activation and ictal RMT was excluded.
Results:   We identified RMT significantly more frequently in FLE patients (48.1%, 26 of 54) than in TLE patients (3.7%, 2 of 54) (p < 0.01), and not in the control group. The average frequency was 6 Hz (range 5–7 Hz), and the average RMT bursts lasted 8 s (3–12 s). Interestingly, all mesial FLE patients (n = 4) (as established by invasive EEG recordings) showed RMT, whereas this was less frequently the case in the other FLE patients (44%, 22 of 50) (p = 0.03). Thirteen of our 54 patients with FLE (24%) did not have any interictal epileptiform discharges (IEDs), but RMT was observed in the majority of these patients (62%, 8 of 13).
Conclusion:   Interictal RMT is common and has a localizing value in patients with FLE, provided that conditions such as drowsiness and mental activation as confounding factors for RMT are excluded. RMT should be included in the evaluation of patients considered for resective epilepsy surgery.     

Alpha-like activity in terminal stage of Creutzfeldt-Jakob disease

We report a case of Creutzfeldt-Jakob disease showing various changes in electroencephalogram (EEG) throughout the course of the disease. The patient's EEG patterns showed periodic synchronous discharge in the intermediate stage of the disease, delta activity in the advanced stage and alpha-like activity in the terminal stage. The mechanism generating alpha-like activity may resemble, at least in part, that of an alpha coma.     

Continuous high-frequency activity in mesial temporal lobe structures

Purpose: Many recent studies have reported the importance of high‐frequency oscillations (HFOs) in the intracerebral electroencephalography (EEG) of patients with epilepsy. These HFOs have been defined as events that stand out from the background. We have noticed that this background often consists itself of high‐frequency rhythmic activity. The purpose of this study is to perform a first evaluation of the characteristics of high‐frequency continuous or semicontinuous background activity. Methods: Because the continuous high‐frequency pattern was noted mainly in mesial temporal structures, we reviewed the EEG studies from these structures in 24 unselected patients with electrodes implanted in these regions. Sections of background away from interictal spikes were marked visually during periods of slow‐wave sleep and wakefulness. They were then high‐passed filtered at 80 Hz and categorized as having high‐frequency rhythmic activity in one of three patterns: continuous/semicontinuous, irregular, sporadic. Wavelet entropy, which measures the degree of rhythmicity of a signal, was calculated for the marked background sections. Key Findings: Ninety‐six bipolar channels were analyzed. The continuous/semicontinuous pattern was found frequently (29/96 channels during wake and 34/96 during sleep). The different patterns were consistent between sleep and wakefulness. The continuous/semicontinuous pattern was found significantly more often in the hippocampus than in the parahippocampal gyrus and was rarely found in the amygdala. The types of pattern were not influenced by whether a channel was within the seizure‐onset zone, or whether it was a lesional channel. The continuous/semicontinuous pattern was associated with a higher frequency of spikes and with high rates of ripples and fast ripples. Significance: It appears that high‐frequency activity (above 80 Hz) does not appear only in the form of brief paroxysmal events but also in the form of continuous rhythmic activity or very long bursts. In this study limited to mesial temporal structures, we found a clear anatomic preference for the hippocampus. Although associated with spikes and with distinct HFOs, this pattern was not clearly associated with the seizure‐onset zone. Future studies will need to evaluate systematically the presence of this pattern, as it may have a pathophysiologic significance and it will also have an important influence on the very definition of HFOs.     

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.     

Sexual auras: predominance of epileptic activity within the mesial temporal lobe

The occurrence of sexual auras (SAs), defined as erotic feelings accompanied by sexual arousal and orgasm, was investigated in 244 consecutive patients with medically refractory focal epilepsy. All patients were evaluated with prolonged video/EEG monitoring, high-resolution MRI, and the Wada test. One female and two male patients with hippocampal sclerosis and /or atrophy experienced SAs. In accordance with the findings on interictal and ictal EEGs, the epileptogenic zone could be localized to the speech-dominant mesial temporal lobe in one case and to the non-speech-dominant mesial temporal lobe in two cases. All patients were treated by selective amygdalohippocampectomy. Our results indicate that: (1) SAs occur in men and women, (2) SAs occur predominantly in seizures originating from the nondominant temporal lobe (but may also be associated with seizure onset in the dominant hemisphere), and (3) SAs point toward a seizure onset in mesial temporal structures.     

Functional changes in temporal lobe activity during transient global amnesia

The integrity of temporal lobe activity during and after recovery from transient global amnesia (TGA) was assessed in a case study using functional MRI. TGA was associated with scene-encoding deficits in a temporolimbic circuit that recovered over time. Frontoparietal areas recruited during the amnesic state may signify a compensatory reliance on visuospatial or working memory strategies. Reduction of extrastriate cortex responses over repeated testing sessions possibly indicates intact visual priming in TGA.     

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.     

Interictal temporal delta activity in temporal lobe epilepsy: correlations with pathology and outcome

PURPOSE: To determine the characteristics and the clinical significance of focal slow activity and its association with focal epileptogenesis in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the interictal EEGs of 141 patients who had temporal lobe resections for intractable focal seizures and correlated the findings with pathologic changes and outcome. The pathologic changes were categorized into medial temporal sclerosis, tumors, and nonspecific changes. RESULTS: Lateralized slow activity was found in 66% of the patients, and it was mainly temporal, of delta frequency and irregular morphology. None of its characteristics, including quantity and reactivity to eye opening, was substrate specific. It was highly concordant with temporal spiking (60%), without any difference across the three groups, but provided additional information in 19 (15%) patients who had no lateralizing spikes. The effect of sleep also was similar in all three groups and included transition of slow waves into spikes. Lateralized slow activity to the side of the operation was significantly associated with favorable outcome only in the group with nonspecific pathology (p = 0.008), regardless of the presence, laterality, or topography of spikes. CONCLUSIONS: Our findings suggest that in patients with TLE whose brain magnetic resonance imaging (MRI) is either normal or suggestive of medial temporal sclerosis, interictal temporal slow activity has a lateralizing value similar to that of temporal spiking. Its association with a favorable outcome in patients with nonspecific pathology also suggests that candidates with lateralizing temporal delta and normal MRI should not be barred from further preoperative assessment.     

Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion

Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background.     

A distinctive electrographic entity: bursts of rhythmical temporal theta

The goal of this study was to investigate the electro-clinical correlations of a distinctive EEG pattern: bursts of rhythmic temporal theta (BORTT). Patients (260) with this pattern were compared to 4 control groups. The peak age in patients with BORTT was in the 50's, appearing especially in black females. The incidence of this pattern in our randomly selected patient group was significantly greater than in a group without evidence of organic cerebral disease. BORTT had a marked preference for the left temporal area (93%), as opposed to the right (30%). In 1/3 of patients, no other EEG finding appeared and in an equal number other mild slow wave abnormalities were seen. Evidence of some kind of vascular disorder (33%) or trauma (16%) was found in nearly 1/2 of the BORTT patients, but the pattern is likely associated with may kinds of etiologies. In conclusion, BORTT likely represents a mild slow wave abnormality, especially of the left temporal lobe in adults, indicating a slight neurophysiological disturbance of varying etiology, but often of vascular origin.     

Temporo-spatial patterns of pre-ictal spike activity in human temporal lobe epilepsy

The statistical properties of pre-ictal EEG spike activity in medial temporal lobe sites were analyzed in 6 patients with medically refractory complex partial seizures. A total of 24 1 h pre-ictal periods (2-6 periods per patient) were evaluated by quantifying the rate of occurrence of individual spatial patterns of spike activity derived from a subset (n = 6) of the recording channels. The channels chosen for analysis always included those medial temporal lobe sites which were documented to be most likely to initiate seizures, as well as their respective contralateral homologues. Each 1 h pre-ictal period was divided into 360 10 sec bins which were then visually classified into 1 of 64 possible spatial patterns of spike activity. These patterns, in turn, were grouped into 1 of 5 general spatial patterns and evaluated for trends across 3 20 min pre-ictal segments. Pooling these data across patients yielded the following results: (1) Focal patterns of spike activity tended to decline significantly in rate of occurrence several minutes prior to seizures, while the rate of independent contralateral patterns did not change. (2) The rate of occurrence of patterns of bilateral loosely coupled spike activity (involving focal and contralateral sites) increased significantly across the 20 min pre-ictal segments and was clearly augmented during the 20 min prior to seizures. These findings indicate that the degree of bilateral independence in medial temporal lobe spike activity tends to decrease several minutes prior to the localized onset of temporal lobe seizures; such changes may reflect the mechanisms responsible for the inter-ictal-ictal transition.     

Cluster analysis detection of functional MRI activity in temporal lobe epilepsy

PURPOSE: The objective of this pilot study was to evaluate the ability of a novel method of cluster analysis, 2dTCA, for identifying and characterizing peak fluctuations in fMRI BOLD signals in the temporal lobes and the default-mode network in temporal lobe epilepsy (TLE) without EEG. METHODS: BOLD fMRI images were acquired in 17 TLE patients and compared to EEG. The timing of significant transient BOLD peaks was estimated by 2dTCA, and activation maps were determined. RESULTS: Sixteen subjects (94%) showed apparent temporal lobe activation. Mesial temporal activation was present in 76.4% (13 patients). Temporal lobe or insula activations were detected ipsilateral to the EEG focus in 64.7% (11 patients), bilaterally with no predominance in 29.4% (5 patients), and exclusively contralateral to the EEG focus in none. Eleven subjects showed activation in the so-called default-mode network including posterior cingulate, bilateral posterior parietal cortex, and sometimes anterior cingulate cortex. CONCLUSIONS: These results demonstrate significant positive BOLD fluctuations in the temporal lobes and default-mode regions in a higher percentage of TLE patients than previously reported using other methods. These fluctuations appear physiologically relevant and suggest increased neural activity which may not be detected on scalp EEG, but which may be important in understanding the mechanisms and origins of epileptic discharges.     

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.     

Suppression of gamma activity in the human medial temporal lobe by sevoflurane anesthesia

We have reported the presence of continuous gamma (30-150 Hz) activity in the human medial temporal lobe (MTL). Since the MTL is involved in learning and memory, we speculated that MTL gamma activity is related to such higher brain functions. It is thus of interest to learn how this activity changes during different states of consciousness. In this study, we recorded electrocorticographic (ECoG) activity directly from the surface of the MTL after various doses of sevoflurane anesthesia. Five epileptic patients underwent electrode placement operations in which electrodes were attached to the surfaces of the MTL and the basal temporal lobe (BTL). Immediately following the operation ECoG was recorded from each patient under four concentrations of sevoflurane anesthesia (1.5, 2.0, 2.5 and 3.0%). Fast Fourier Transform (FFT) analysis was performed on the MTL ECoGs. Under the lowest sevoflurane concentration, MTL gamma activity was observed in all patients. However, gamma activity was progressively suppressed by increased concentrations of sevoflurane, in a dose-dependent manner. Sevoflurane has been known to reduce neuronal excitability in the rat hippocampus in vitro, probably by changing GABAergic inhibition. The reduction of MTL gamma in the present study may be the result of such a mechanism. Although memory function was not tested in this study, the amount of MTL gamma activity may be related to residual memory function during anesthesia.     

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”.