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.     

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.     

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.     

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.     

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.     

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.     

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.     

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...     

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.     

基于ReHo方法的颞叶癫痫功能磁共振成像研究

癫痫是一种以神经活动同步性异常增高为特征的中枢神经系统疾病。作者利用基于局域一致性(regional homogeneity,ReHo)分析方法的功能磁共振成像技术对内侧颞叶癫痫(medial temporal lobe epilepsy,mTLE)进行了研究。观察颞叶癫痫病人相比正常对照组局域一致性的改变情况。结果表明:在静息状态下,病人大脑的局域一致性在某些脑区较正常人高,主要集中在海马、丘脑、顶叶;另外在某些脑区的局域一致性较正常人低,主要集中在小脑后叶。提示该方法可检出癫痫活动造成的局部脑组织血氧水平信号同步性的改变,进而达到对癫痫活动的定位检测。     

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.     

Which clinical and experimental data link temporal lobe epilepsy with depression?

The association of temporal lobe epilepsy with depression and other neuropsychiatric disorders has been known since the early beginnings of neurology and psychiatry. However, only recently have in vivo and ex vivo techniques such as Positron Emission Tomography, Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy in combination with refined animal models and behavioral tests made it possible to identify an emerging pattern of common pathophysiological mechanisms. We now have growing evidence that in both disorders altered interaction of serotonergic and noradrenergic neurons with glutamatergic systems is associated with abnormal neuronal circuits and hyperexcitability. Neuronal hyperexcitability can possibly evoke seizure activity as well as disturbed emotions. Moreover, decreased synaptic levels of neurotransmitters and high glucocorticoid levels influence intracellular signaling pathways such as cAMP, causing disturbances of brain-derived and other neurotrophic factors. These may be associated with hippocampal atrophy seen on Magnetic Resonance Imaging and memory impairment as well as altered fear processing and transient hypertrophy of the amygdala. Positron Emission Tomography studies additionally suggest hypometabolism of glucose in temporal and frontal lobes. Last, but not least, in temporal lobe epilepsy and depression astrocytes play a role that reaches far beyond their involvement in hippocampal sclerosis and ultimately, therapeutic regulation of glial-neuronal interactions may be a target for future research. All these mechanisms are strongly intertwined and probably bidirectional such that the structural and functional alterations from one disease increase the risk for developing the other. This review provides an integrative update of the most relevant experimental and clinical data on temporal lobe epilepsy and its association with depression.     

癫痫与海马结构的改变

癫痫作为一种严重危害人类健康的常见病、多发病，其致病机理至今尚未阐明。30—60％的患者药物治疗无效，称“难治性癫痫”。随着现代医学的发展，外科手术的开展对于癫痫患者治疗也没有满意的效果。这就对于我们探求癫痫患者病灶的起源有了更深层次的要求。大量动物实验表明，海马作为中枢神经系统的重要结构不仅同学习、记忆、情绪等密切相关，还同癫痫的发生发展有着重要的联系。本文就大脑可塑性与癫痫的关系进行综述。     

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.     

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.     

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.     

Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABA_A Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.     

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.     

Gelsolin in Cerebrospinal Fluid as a Potential Biomarker of Epilepsy

Gelsolin is an actin regulatory protein that generally distributed in a wide variety of body tissues, especially the brain tissues and cerebrospinal fluid. In this study we found that lumbar CSF-gelsolin concentrations markedly decreased in epileptic patients by enzyme linked immunosorbent assay. In order to help judge the result, we determined gelsolin expression in temporal lobe tissues of patients with temporal lobe epilepsy using double-label immunofluorescence to location and using western blot to quantitation. Then we observed that gelsolin was co-expressed with microtubule-associated protein-2 in axons and cytoplasms of neurons and gelsolin protein level was also down-regulated in temporal lobe tissues of epileptic patients. Our findings suggested that CSF-gelsolin level might reflect the alteration of gelsolin in brain tissue of epileptic patients and CSF-gelsolin seems to be a potential biomarker for epilepsy.