Temporal Lobe Epilepsy: A Clinical Study of 47 Cases

Clinical features of 47 cases of temporal lobe epilepsy are analyzed and treatment of this disorder is outlined. Twenty-four per cent of all cases of epilepsy seen by one of the authors over a two-year period were of this type. Fifteen of these 47 patients had a history of birth injury. Care must be taken to distinguish the symptoms of temporal lobe epilepsy from those of acute anxiety or hysteria and to differentiate the short-lived temporal lobe attack from centrencephalic petit mal.Interictal personality disturbances were identified in 11 of 24 persons with temporal lobe epilepsy, four of 35 with focal epilepsy from all other areas, and one of 17 with centrencephalic epilepsy. Personality deviations most frequently encountered were irritability, aggressiveness, bouts of depression, paranoid tendencies and exhibitionism. Medical or surgical treatment often improves the personality abnormalities concomitantly with control of seizures.     

Effect of EEG Biofeedback on Cognitive Flexibility in Children with Attention Deficit Hyperactivity Disorder With and Without Epilepsy

Attention deficit hyperactivity disorder (ADHD) is one of the most common developmental disorders in school-aged children. Symptoms consistent with ADHD have been observed in 8–77 % of children with epilepsy. Researchers have been motivated to search for alternative forms of treatment because 30 % of patients with ADHD cannot be treated by psychostimulants. Several studies support the use of a multimodal treatment approach that includes neurofeedback (NF) for the long-term management of ADHD. These studies have shown that NF provides a sustained effect, even without concurrent treatment with stimulants. We aimed to assess cognitive flexibility in ADHD children with and without temporal lobe epilepsy (TLE), and to evaluate the effects of NF on cognitive flexibility in these groups of children. We prospectively evaluated 69 patients with ADHD aged 9–12 years. The control group was 26 ADHD children without TLE who received no treatment. The first experimental group comprised 18 children with ADHD. The second experimental group comprised 25 age-matched ADHD children with TLE. This group was further divided in two subgroups. One subgroup comprised those with mesial temporal lobe epilepsy (16 patients, 9 with hippocampal sclerosis and 7 with hippocampal atrophy), and the other with lateral temporal lobe epilepsy (9 patients, 5 with temporal lobe dysplasia, 3 with temporal lobe cysts, and 1 with a temporal lobe cavernoma). We treated their ADHD by conducting 30 sessions of EEG NF. Reaction time and error rates on the Trail Making Test Part B were compared before and after treatment, and significant differences were found for all groups of patients except those who had mesial temporal lobe epilepsy with hippocampal atrophy. Our results demonstrate that in most cases, NF can be considered an alternative treatment option for ADHD children even if they have TLE. Additional studies are needed to confirm our results.     

Differential Diagnosis of Transient Amnesia

In a group of 39 consecutive patients attending neurological clinics with transient amnesia patients with transient global amnesia formed the largest group; others suffered from epilepsy, migraine, temporal lobe encephalitis, or psychogenic fugues. In most cases the clinical features suggested the aetiology, but an electroencephalogram recorded as soon after the attack as possible may help in distinguishing amnesia due to temporal lobe epilepsy.     

Long-Term Effects of Temporal Lobe Epilepsy on Local Neural Networks: A Graph Theoretical Analysis of Corticography Recordings

Purpose

Pharmaco-resistant temporal lobe epilepsy (TLE) is often treated with surgical intervention at some point. As epilepsy surgery is considered a last resort by most physicians, a long history of epileptic seizures prior to surgery is not uncommon. Little is known about the effects of ongoing TLE on neural functioning. A better understanding of these effects might influence the moment of surgical intervention. Functional connectivity (interaction between spatially distributed brain areas) and network structure (integration and segregation of information processing) are thought to be essential for optimal brain functioning. We report on the impact of TLE duration on temporal lobe functional connectivity and network characteristics.

Methods

Functional connectivity of the temporal lobe at the time of surgery was assessed by means of interictal electrocorticography (ECoG) recordings of 27 TLE patients by using the phase lag index (PLI). Graphs (abstract network representations) were reconstructed from the PLI matrix and characterized by the clustering coefficient C (local clustering), the path length L (overall network interconnectedness), and the “small world index” S (network configuration).

Results

Functional connectivity (average PLI), clustering coefficients, and the small world index were negatively correlated with TLE duration in the broad frequency band (0.5–48 Hz).

Discussion

Temporal lobe functional connectivity is lower in patients with longer TLE history, and longer TLE duration is correlated with more random network configuration. Our findings suggest that the neural networks of TLE patients become more pathological over time, possibly due to temporal lobe changes associated with long-standing lesional epilepsy.     

Kainic acid as a tool for the study of temporal lobe epilepsy

Temporal lobe epilepsy (limbic epilepsy, complex partial epilepsy, psychomotor epilepsy) is the most devastating form of epilepsy commonly encountered in the adult population. The attacks involve loss of consciousness, thus limiting performance of normal functions and exposing the individual to bodily injury. Moreover, long-standing or pharmacologically intractable temporal lobe epilepsy is frequently associated with the loss of neurons from the hippocampus and other brain regions (Ammon's horn sclerosis (AHS)). Unfortunately, pharmacologically intractable cases are rather common, owing to the relatively low efficacy against this condition of the available anticonvulsants. Progress in the understanding and treatment of temporal lobe epilepsy would be greatly facilitated by the availability of an animal model which reproduced the behavioral, electrographic and pathological features of this condition. Here I review evidence which indicates that the kainic acid (KA)-treated rat possesses many of the features required of such a model.     

Endocrine abnormalities in human temporal lobe epilepsy

Patients with temporal lobe epilepsy secrete ACTH at higher rates and in greater amounts than normal subjects. Temporal lobectomy restores ACTH secretion to normal amounts and rates. The ACTH secretion in temporal lobe epilepsy is independent of anticonvulsant drug effect and seizure frequency. Electrical stimulation of medial temporal lobe structures in patients with temporal lobe epilepsy affected ACTH secretion in a manner consistent with the hypothesis that ACTH secretion is regulated by tonic inhibition. A defect in the excitatory and/or inhibitory components of this regulatory process appears to exist in temporal lobe epilepsy.     

Ensembles of human MTL neurons "jump back in time" in response to a repeated stimulus

Episodic memory, which depends critically on the integrity of the medial temporal lobe (MTL), has been described as "mental time travel" in which the rememberer "jumps back in time." The neural mechanism underlying this ability remains elusive. Mathematical and computational models of performance in episodic memory tasks provide a specific hypothesis regarding the computation that supports such a jump back in time. The models suggest that a representation of temporal context, a representation that changes gradually over macroscopic periods of time, is the cue for episodic recall. According to these models, a jump back in time corresponds to a stimulus recovering a prior state of temporal context. In vivo single-neuron recordings were taken from the human MTL while epilepsy patients distinguished novel from repeated images in a continuous recognition memory task. The firing pattern of the ensemble of MTL neurons showed robust temporal autocorrelation over macroscopic periods of time during performance of the memory task. The gradually-changing part of the ensemble state was causally affected by the visual stimulus being presented. Critically, repetition of a stimulus caused the ensemble to elicit a pattern of activity that resembled the pattern of activity present before the initial presentation of the stimulus. These findings confirm a direct prediction of this class of temporal context models and may be a signature of the mechanism that underlies the experience of episodic memory as mental time travel. ? 2012 Wiley Periodicals, Inc.     

Comparative characteristics of spatial hearing of patients with different forms of cortical epilepsy

Perception of signals modeling directed movement of a sound source by three groups of patients with (1) temporal epilepsy, (2) epileptic foci in the frontal region, and (3) the epileptic syndrome due to local organic lesions in the temporal or frontal lobes was studied. It was established that the features and degree of spatial (binaural) hearing disorders in temporal epilepsy were determined not only by the localization and the extent of a lesion in the temporal lobe, but also by the areas beyond it that were involved in the epileptic process. Patients with organic lesions (tumors, cysts) involving the temporal lobe cortex may reveal more severe spatial hearing disorders than temporal epilepsy patients with the same localization of the foci of convulsive activity. A relatively isolated lesion of the frontal region cortex does not influence the assessment of the parameters of moving sound signals used. Possible neurophysiological mechanisms underlying the found spatial hearing disorders as well as the possibility of using the results obtained to solve the problems of differential diagnosis are considered.     

PSYCHIATRIC ASPECTS OF PSYCHOMOTOR EPILEPSY

Psychomotor or temporal lobe epilepsy is a frequently missed diagnosis. It is often confused with grand mal and petit mal epilepsy. At times it is the first symptom of an organic neurological disease. It is often masked as a psychiatric disorder or is associated with a mental illness without clinically detectable seizures.These psychic manifestations simulate all of the neuroses and major psychiatric states. Excitement states with amnesia may lead to violent antisocial behavior. All these manifestations may be aggravated by alcohol.Thalamic epilepsy shows itself in similar psychiatric manifestations and accounts for behavior disorder in children more than temporal lobe epilepsy. Atypical seizures with vegetative or emotional aura and a characteristic electroencephalogram differentiate it from temporal lobe epilepsy.Proper understanding of the varied manifestations, with positive electroencephalographic findings, leads to the correct diagnosis in most cases. All patients with unusual or atypical personality or psychiatric-like states should have careful electroencephalographic examination. Anticonvulsant therapy and other psychiatric treatment procedures can relieve most cases. Surgical therapy sometimes is necessary.     

Whole mitochondrial DNA variations in hippocampal surgical specimens and blood samples with high-throughput sequencing: A case of mesial temporal lobe epilepsy with hippocampal sclerosis

Introduction

Hippocampal sclerosis is the most common lesion in patients with mesial temporal lobe epilepsy. Recently, there has been growing evidence on the involvement of mitochondria also in sporadic forms of epilepsy. In addition, it has been increasingly argued that mitochondrial dysfunction has an important role in epileptogenesis and seizure generation in temporal lobe epilepsy. Although mtDNA polymorphisms have been identified as potential risk factors for neurological diseases, the link between homoplasmy and heteroplasmy within tissues is not clear. We investigated whether mitochondrial DNA (mtDNA) polymorphisms are involved in a case report of a patient with mesial temporal lobe epilepsy-hippocampal sclerosis (MTLE-HS).

Design

We report the whole genome mtDNA deep sequencing results and clinical features of a 36-year-old woman with MTLE-HS. We used pyrosequencing technology to sequence a whole mitochondrial genome isolated from six different regions of her brain and blood. To assess the possible role of mitochondrial DNA variations in affected tissues, we compared all specimens from different regions of the hippocampus and blood.

Results

In total, 35 homoplasmic and 18 heteroplasmic variations have been detected in 6 different regions of the hippocampus and in blood samples. While the samples did not display any difference in homoplasmic variations, it has been shown that hippocampus regions contain more heteroplasmic variations than blood. The number of heteroplasmic variations was highest in the CA2 region of the brain and accumulated in ND2, ND4 and ND5 genes. Also, dentate and subiculum regions of the hippocampus had similar heteroplasmic variation profiles.

Discussion

We present a new rare example of parallel mutation at 16223 position. Our case suggests that defects in mitochondrial function might be underlying the pathogenesis of seizures in temporal lobe epilepsy.     

Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis

This study aimed to determine if there is an association between mitophagy and refractory temporal lobe epilepsy (rTLE) with hippocampal sclerosis. During epilepsy surgery, we collected tissue samples from the hippocampi and temporal lobe cortexes of rTLE patients with hippocampal sclerosis (as diagnosed by a pathologist). Transmission electron microscopy (TEM) was used to study the ultrastructural features of the tissue. To probe for mitophagy, we used fluorescent immunolabeling to determine if mitochondrial and autophagosomal markers colocalized. Fourteen samples were examined. TEM results showed that early autophagosomes were present and mitochondria were impaired to different degrees in hippocampi. Immunofluorescent labeling showed colocalization of the autophagosome marker LC3B with the mitochondrial marker TOMM20 in hippocampi and temporal lobe cortexes, indicating the presence of mitophagy. Mitochondrial and autophagosomal marker colocalization was lower in hippocampus than in temporal lobe cortex (P < 0.001). Accumulation of autophagosomes and mitophagy activation are implicated in rTLE with hippocampal sclerosis. Aberrant accumulation of damaged mitochondria, especially in the hippocampus, can be attributed to defects in mitophagy, which may participate in epileptogenesis.     

Wnt/β‐catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid‐induced epilepsy

Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis with massive neuronal loss and severe gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant neurogenesis remain unclear. The roles of Wnt signalling cascade have been well established in neurogenesis during multiple aspects. Here, we used kainic acid‐induced rat epilepsy model to investigate whether Wnt/β‐catenin signalling pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy. Immunostaining and western blotting results showed that the expression levels of β‐catenin, Wnt3a, and cyclin D1, the key regulators in Wnt signalling pathway, were up‐regulated during acute epilepsy induced by the injection of kainic acids, indicating that Wnt signalling pathway was activated in kainic acid‐induced temporal lobe epilepsy. Moreover, BrdU labelling results showed that blockade of the Wnt signalling by knocking down β‐catenin attenuated aberrant neurogenesis induced by kainic acids injection. Altogether, Wnt/β‐catenin signalling pathway mediated hippocampal neurogenesis during epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis. Aberrant neurogenesis has been shown to involve in the epileptogenesis process of temporal lobe epilepsy. In the present study, we discovered that Wnt3a/β‐catenin signalling pathway serves as a link between aberrant neurogenesis and underlying remodelling in the hippocampus, leading to temporal lobe epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy.     

Expression of SHANK3 in the Temporal Neocortex of Patients with Intractable Temporal Epilepsy and Epilepsy Rat Models

SH3 and multiple ankyrin (ANK) repeat domain 3 (SHANK3) is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. SHANK3 plays an important role in the formation and maturation of excitatory synapses. In the brain, SHANK3 directly or indirectly interacts with various synaptic molecules including N-methyl-D-aspartate receptor, the metabotropic glutamate receptor (mGluR), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Previous studies have shown that Autism spectrum disorder is a result of mutations of the main SHANK3 isoforms, which may be due to deficit in excitatory synaptic transmission and plasticity. Recently, accumulating evidence has demonstrated that overexpression of SHANK3 could induce seizures in vivo. However, little is known about the role of SHANK3 in refractory temporal lobe epilepsy (TLE). Therefore, we investigated the expression pattern of SHANK3 in patients with intractable temporal lobe epilepsy and in pilocarpine-induced models of epilepsy. Immunofluorescence, immunohistochemistry, and western blot analysis were used to locate and determine the expression of SHANK3 in the temporal neocortex of patients with epilepsy, and in the hippocampus and temporal lobe cortex of rats in a pilocarpine-induced epilepsy model. Double-labeled immunofluorescence showed that SHANK3 was mainly expressed in neurons. Western blot analysis confirmed that SHANK3 expression was increased in the neocortex of TLE patients and rats. These results indicate that SHANK3 participates in the pathology of epilepsy.     

The Stigma of Migraine

Background

People who have a disease often experience stigma, a socially and culturally embedded process through which individuals experience stereotyping, devaluation, and discrimination. Stigma has great impact on quality of life, behavior, and life chances. We do not know whether or not migraine is stigmatizing.

Methods

We studied 123 episodic migraine patients, 123 chronic migraine patients, and 62 epilepsy patients in a clinical setting to investigate the extent to which stigma attaches to migraine, using epilepsy as a comparison. We used the stigma scale for chronic illness, a 24-item questionnaire suitable for studying chronic neurologic diseases, and various disease impact measures.

Results

Patients with chronic migraine had higher scores (54.0±20.2) on the stigma scale for chronic illness than either episodic migraine (41.7±14.8) or epilepsy patients (44.6±16.3) (p<0.001). Subjects with migraine reported greater inability to work than epilepsy subjects. Stigma correlated most strongly with the mental component score of the short form of the medical outcomes health survey (SF-12), then with ability to work and migraine disability score for chronic and episodic migraine and the Liverpool impact on epilepsy scale for epilepsy. Analysis of covariance showed adjusted scores for the stigma scale for chronic illness were similar for chronic migraine (49.3; 95% confidence interval, 46.2 to 52.4) and epilepsy (46.5; 95% confidence interval, 41.6 to 51.6), and lower for episodic migraine (43.7; 95% confidence interval, 40.9 to 46.6). Ability to work was the strongest predictor of stigma as measured by the stigma scale for chronic illness.

Conclusion

In our model, adjusted stigma was similar for chronic migraine and epilepsy, which were greater than for episodic migraine. Stigma correlated most strongly with inability to work, and was greater for chronic migraine than epilepsy or episodic migraine because chronic migraine patients had less ability to work.     

A Mesiotemporal Lobe Epilepsy Mouse Model

Among the different forms of epilepsies, mesiotemporal lobe epilepsy (MTLE) is one of the most common and represents the main pharmaco-resistant form of epilepsy. There is therefore an urgent need to better understand this form of epilepsy to develop better anti-epileptic drugs. Many rodent models are mimicking some aspects of the human temporal lobe epilepsy but only few are addressing most of the human mesiotemporal lobe epilepsy. In this article, we describe the main characteristics of a mouse of model of mesial temporal lobe epilepsy. This model is generated by a single injection of kainic acid into the dorsal hippocampus which reproduces most of the morphological and electrophysiological features of human MTLE in a mouse. This model may help to better understand mesial temporal lobe epilepsy and the development of new therapeutic drugs.     

Resting-state EEG source localization and functional connectivity in schizophrenia-like psychosis of epilepsy

Background

It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits.

Methodology/Principal Findings

Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called “lagged phase synchronization” was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca''s area correlating with auditory hallucination scores.

Conclusions/Significance

In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.     

Developing a new animal model of temporal lobe epilepsy

Epilepsy affects 1-2 % of the population. For 30 % of these patients, their syndrome will be refractory to medical treatment. To improve our understanding and treatment of the epilepsies, we need to develop clinically relevant animal models. As temporal lobe epilepsy is often preceded by prolonged febrile seizures and in our population associated with a focal cortical dysplasia, we hypothesised that an underlying predisposing anatomical lesion would predispose individuals to develop prolonged febrile seizures and that temporal lobe epilepsy would later develop. As predicted, all the lesioned animals developed prolonged febrile seizures, while all other control groups only showed simple febrile seizures. After a latent period, 86 % of the animals who had experienced a prolonged seizure developed spontaneously recurrent limbic seizures. We now need to understand the anatomical and electrophysiological changes underlying this new epilepsy model to try and develop more effective treatments for the condition.     

Functional Connectivity Estimated from Intracranial EEG Predicts Surgical Outcome in Intractable Temporal Lobe Epilepsy

This project aimed to determine if a correlation-based measure of functional connectivity can identify epileptogenic zones from intracranial EEG signals, as well as to investigate the prognostic significance of such a measure on seizure outcome following temporal lobe lobectomy. To this end, we retrospectively analyzed 23 adult patients with intractable temporal lobe epilepsy (TLE) who underwent an invasive stereo-EEG (SEEG) evaluation between January 2009 year and January 2012. A follow-up of at least one year was required. The primary outcome measure was complete seizure-freedom at last follow-up. Functional connectivity between two areas in the temporal lobe that were sampled by two SEEG electrode contacts was defined as Pearson’s correlation coefficient of interictal activity between those areas. SEEG signals were filtered between 5 and 50 Hz prior to computing this correlation. The mean and standard deviation of the off diagonal elements in the connectivity matrix were also calculated. Analysis of the mean and standard deviation of the functional connections for each patient reveals that 90% of the patients who had weak and homogenous connections were seizure free one year after temporal lobectomy, whereas 85% of the patients who had stronger and more heterogeneous connections within the temporal lobe had recurrence of seizures. This suggests that temporal lobectomy is ineffective in preventing seizure recurrence for patients in whom the temporal lobe is characterized by weakly connected, homogenous networks. This pilot study shows promising potential of a simple measure of functional brain connectivity to identify epileptogenicity and predict the outcome of epilepsy surgery.     

Medical Aspects of Violence

Physicians see violence in beaten wives, battered children, rage reactions, murder, and suicide. They should recognize that it may be a symptom of disease if it is unprovoked or bizarre, or is associated with impaired consciousness, confusion or irrationality. Violence in episodic trance-like states suggests limbic disease (temporal lobe lesions, psychomotor epilepsy, or “dyscontrol syndrome”); in association with personality change, dementia, or psychosis, it indicates cortical disease (structural, toxic, or idiopathic).