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.     

Epileptic dizziness.

Clinical and electroencephalographic features and the response to treatment of 30 patients with episodic dizziness due to epilepsy were noted. The symptom consisted of a brief episode of disequilibrium, often with a sensation of rotation, without evident precipitating factors or sequelae. A history of "absences" or other features suggestive of temporal lobe epilepsy was elicited in over half the patients, and seven (almost a quarter) had had one or more generalized seizures before presentation. Electroencephalography showed a posterior temporal lobe focus in all but two patients, and there was a family history of epilepsy in six. Response to treatment with phenytoin or carbamazepine was good in most patients. Epilepsy should be considered in the differential diagnosis of episodic dizziness or vertigo, especially in young people.     

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.     

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.     

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.     

Clinical Aspects of Temporal Lobe Epilepsy

Temporal lobe epilepsy appears to be of increasing concern to psychiatrists, pediatricians and lawyers as an explanation for some aspects of behavior. There is a high incidence of structural abnormality associated with temporal lobe epilepsy, the most common being mesial temporal sclerosis. Depth electrode studies have shown that the most common focus for the clinical seizure is in the hippocampus or hippocampal gyrus. The first line of treatment continues to be attempt at control with anticonvulsant agents. Surgical treatment can be offered, in many instances, when drug therapy has failed.     

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.     

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.     

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.     

Characterization of synchronization in interacting groups of oscillators: application to seizures

We investigate the emergence of synchronization in two groups of oscillators; one group acts as a synchronization source, and the other as the target. Based on phase model simulations, we construct a synchrony index (SI): a combination of intra- and intergroup synchronies. The SI characterizes the extent of induced synchrony in the population. We demonstrate the usefulness of the measure in a test case of mesial temporal lobe epilepsy: the SI can be readily calculated from standard electroencephalographic measurements. We show that the synchrony index has a statistically significant increased value for the ictal periods and that the epileptic focus can be located by identifying the most synchronous pairs of electrodes during the initial part of ictal period of the seizure. We also show that it is possible in this pilot case to differentiate clinical and subclinical seizures based on the dynamical features of the synchronization. The synchronization index was found to be a useful quantity for the characterization of “pathological hypersynchronization” within a well-characterized patient with mesial temporal lobe epilepsy and thus has potential medical value in seizure detection, localizing ability, and association with later surgical outcome.     

颞叶癫痫脑“默认模式”的fMRI研究

功能磁共振成像(functional magnetic resonance imaging,fMRI)被用于检测静息时脑功能神经网络.作者运用静息fMRI检测海马硬化颞叶癫痫(temporal lobe epilepsy,TLE)脑"默认模式",采用感兴趣区域功能连接分析检测16例TLE患者和16名正常对照静息时脑的"默认模式",并进行组内和组间分析.研究发现,与正常对照相比,TLE静息时海马、颞极、额叶、颞叶、壳核及楔前叶等脑区与后扣带回的功能连接增强.研究结果表明TLE患者的固有脑功能组织模式有可能出现紊乱.这一研究将有助于从脑功能的角度了解癫痫患者某些临床症状的发病机理,为今后癫痫诊治的发展提供一定的帮助.     

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.     

Dissociation, forced normalization and dynamic multi-stability of the brain

Dissociated states represent pathological conditions where psychological trauma may emerge in a variety of forms such as psychic dissociative symptoms (hallucinations, derealization etc.) or on the other hand as somatoform symptoms (paroxysms, loss of motor control, involuntary movements etc.). Recent findings suggest that neurophysiological level of dissociative phenomena may be linked to the same neurophysiological principles that emerge in multi-stable perception of ambiguous stimuli likely caused by competing interpretations with mutual exclusivity. At this time there is evidence that temporal lobe seizure activity can produce dissociative syndrome and from these findings may be inferred that temporal lobe epileptic activity existing independently of neurological focal may share common neurobiological mechanism with dissociative symptoms. This conceptualization of dissociative phenomena is also in accordance with findings that originate from the study of the relationship between epilepsy and mental illness. The relationship was for the first time described in Meduna's concept of antagonism between epilepsy and psychosis and from the study of forced normalization introduced by Landolt in 1950s. The findings reported similar pathological conditions as in dissociative states when psychopathological symptoms and paroxysms may represent two different forms of the pathological process. Following the concept of forced normalization Tellenbach in 1965 introduced the term alternative psychosis implicating that stopping seizures does not mean vanishing or inactivity of the pathological state and that the epilepsy is still active subcortically and supplies energy for psychopathological symptoms. In the present review chaos in brain neural networks as a possible explanation of the relationship between dissociation and epileptic activity has been suggested that represents testable hypothesis for future research.     

Stress-Associated Molecular and Cellular Hippocampal Mechanisms Common for Epilepsy and Comorbid Depressive Disorders

Biochemistry (Moscow) - The review discusses molecular and cellular mechanisms common to the temporal lobe epileptogenesis/epilepsy and depressive disorders. Comorbid temporal lobe epilepsy and...     

Correlation between fluidity and fatty acid composition of phospholipid species in Tetrahymena pyriformis during temperature acclimation.

The correlation between the fluidity of phospholipids and their fatty acid composition was studied by spin label technique and gas-liquid chromatography for three major phospholipid species in Tetrahymena pyriformis during temperature acclimation. The fluidity of 2-aminoethylphosphonolipid increased within the first 10 h of the cold-acclimation when the content of gamma-linolenic acid in 2-aminoethylphosphonolipid was highest, and it then decreased up to 24 h. On the other hand, the fluidities of phosphatidylethanolamine and phosphatidylcholine showed a gradual decrease up to 24 h after the temperature shift, although gamma-linolenic acid contents were highest at 10 h after the temperature shift. Thus the fluidity changes of these two phospholipids were interpreted as resulting from the altered content of other fatty acids in addition to gamma-linolenic acid, since the gamma-linolenic acid content was smaller than that of 2-aminoethylphosphonolipid. The results suggest that the content of gamma-linolenic acid in 2-aminoethylphosphonolipid plays a role in regulating the thermal adaptation process.     

Concomitant Fractional Anisotropy and Volumetric Abnormalities in Temporal Lobe Epilepsy: Cross-Sectional Evidence for Progressive Neurologic Injury

Background

In patients with temporal lobe epilepsy and associated hippocampal sclerosis (TLEhs) there are brain abnormalities extending beyond the presumed epileptogenic zone as revealed separately in conventional magnetic resonance imaging (MRI) and MR diffusion tensor imaging (DTI) studies. However, little is known about the relation between macroscopic atrophy (revealed by volumetric MRI) and microstructural degeneration (inferred by DTI).

Methodology/Principal Findings

For 62 patients with unilateral TLEhs and 68 healthy controls, we determined volumes and mean fractional anisotropy (FA) of ipsilateral and contralateral brain structures from T1-weighted and DTI data, respectively. We report significant volume atrophy and FA alterations of temporal lobe, subcortical and callosal regions, which were more diffuse and bilateral in patients with left TLEhs relative to right TLEhs. We observed significant relationships between volume loss and mean FA, particularly of the thalamus and putamen bilaterally. When corrected for age, duration of epilepsy was significantly correlated with FA loss of an anatomically plausible route - including ipsilateral parahippocampal gyrus and temporal lobe white matter, the thalamus bilaterally, and posterior regions of the corpus callosum that contain temporal lobe fibres - that may be suggestive of progressive brain degeneration in response to recurrent seizures.

Conclusions/Significance

Chronic TLEhs is associated with interrelated DTI-derived and volume-derived brain degenerative abnormalities that are influenced by the duration of the disorder and the side of seizure onset. This work confirms previously contradictory findings by employing multi-modal imaging techniques in parallel in a large sample of patients.     

Effect of oxcarbazepine pretreatment on convulsive activity and brain damage induced by kainic acid administration in rats

Temporal lobe epilepsy is one of the most common types of epilepsy. Progress in the understanding and treatment of this type of epilepsy would be greatly facilitated by the availability of an animal model, which reproduced the behavioral and electrographic features of this condition. In this context, kainic acid (KA, 2-carboxy-3-carboxymethyl-4-isopropenylpyrrolidine) administration causes a syndrome characterized by an acute status epilepticus and subsequent brain damage similar to that in temporal lobe epilepsy of humans. The aim of the present study was to investigate whether oxcarbazepine (10,11-dihydro-10-oxo-5 H -dibenz(b,f)azepine-5-carboxamide), an antiepileptic drug, protects against both epileptic activity and brain damage induced by KA administration. Chronically implanted adult male Wistar rats were polygraphically recorded during 10 continuous hours under 4 different conditions: a) control, b) after KA administration alone, c) after KA administration in oxcarbazepine pretreated animals and d) after the administration of oxcarbazepine alone. Animals treated with KA alone presented behavioral and electrophysiological convulsive activity as well as brain damage. Latency of seizure installation was lengthened significantly and convulsive activity was slightly reduced, however, brain damage was still present in oxcarbazepine pretreated animals. Administration of oxcarbazepine alone induced a hypnotic behavior and brain damage was also present.     

Extraction of reproducible seizure patterns based on EEG scalp correlations

The objective of this work is to identify similarities in the spatio-temporal dynamics of epileptic seizures, record with scalp EEG. A comprehensive method is proposed and applied in EEG of the patients who suffer from temporal lobe epilepsy. The method is based on the computation of the time-varying degree of non linear correlation between scalp electrodes at seizure onset and during seizure spread, determined by a nonlinear regression analysis. The quantification and coding of these similarity relations allow the comparison between two epileptic networks. Results show that reproducible patterns may be extracted from different seizures of the same patient and confirm the existence of different subtypes of temporal lobe epilepsy.     

Effect of glutamic acid on the fatty acid and lipid composition of Choanephora cucurbitarum.

The fatty acid composition of the total, neutral, sterol, free fatty acid, and polar-lipid fractions in the mycelium of Choanephora curcurbitarum was determined. The major fatty acids in all lipid fractions were palmitic, oleic, linoleic, and gamma-linolenic acid. Different lipid fractions did not show any particular preference for any individual fatty acid; however, the degree of unsaturation was different in different lipid fractions. Free fatty acid and polar lipid fractions contained a higher proportion of gamma-linolenic acid than did triglyceride and sterol fractions. Addition of glutamic acid to the malt-yeast extract and medium resulted in the biosynthesis of a number of long-chain fatty acids beyond the gamma-linolenic acid. These fatty acids, e.g., C22:1, C24:0, and C26:0, were never observed to be present in the fungus when grown on a malt-yeast extract medium without glutamic acid. Furthermore, thin-layer chromatographic analysis showed a larger and denser spot of diphosphatidyl glycerol from the mycelium grown on glutamic acid medium than from the control mycelium. The possible significance of this finding is discussed.     

Laboratory animal models of temporal lobe epilepsy

Temporal lobe epilepsy is a common human disease that is difficult to treat. The pathogenesis of temporal lobe epilepsy, which holds many unresolved questions, and opportunities for creating more effective treatments and preventative strategies are reviewed herein. Laboratory animal models are essential to meet these challenges. How models are created, how they compare with each other and with the disease in human patients, and how they advance our understanding of temporal lobe epilepsy are described.