The epidemiology of the epilepsies in children

The epilepsies are a heterogeneous collection of neurological conditions and syndromes characterized by recurrent, unprovoked, paroxysmal seizure activity. There are several types of epileptic seizures and syndromes that are unique to children, including infantile spasms, Lennox-Gastaut syndrome and absence seizures. Febrile seizures and neonatal seizures, while not epilepsy, are relatively common types of seizures in infants and children and are likely markers of risk of later epilepsy. Thus, it is important to consider the epidemiological features of the epilepsies as they occur specifically in infants and children. The purpose of this review is to summarize what is currently known about the epidemiology of the childhood epilepsies and to identify promising areas for further population-based studies. The epilepsies are an important cause of neurological morbidity in children. The average annual rate of new cases (incidence) of epilepsy is approximately 5-7 cases per 10,000 children from birth to age 15 years, and in any given year, about 5 of every 1,000 children will have epilepsy. There is evidence that the incidence of the epilepsies in some populations of children may be decreasing over time, and this possibility merits further investigation. Factors that are known to increase risk of the epilepsies in children include congenital malformations of the central nervous system (CNS), moderate or severe head trauma, CNS infections, certain inherited metabolic conditions, and genetic factors. However, these account for only 25% to 45% of cases, and thus, the etiology of most cases of the epilepsies remains obscure. The paucity of well-controlled etiological studies is due largely to formidable methodological problems in conducting epidemiological studies of the epilepsies. The prognosis for seizure control is generally good, although children with remote symptomatic seizures and those with additional neurological disabilities do less well.     

Neuropsychological Deficits in Childhood Epilepsy Syndromes

Seizure disorders are relatively common in childhood, and the International League Against Epilepsy (ILAE) provides a hierarchical classification system to define seizure types. At the final level of classification, specific epilepsy syndromes are defined that represent a complex of signs and symptoms unique to an epilepsy condition. The present review discusses the issues related to several of these epilepsy syndromes in childhood, including those classified as generalized idiopathic epilepsies (e.g., childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy), focal epilepsies (benign rolandic epilepsy, occipital epilepsy, temporal lobe epilepsy, frontal lobe epilepsy) and the "epileptic encephalopathies," including Dravet's Syndrome, West Syndrome, Lennox-Gastaut Syndrome, Myoclonic Astatic Epilepsy, and Landau-Kleffner Syndrome. For each syndrome, the epidemiology, clinical manifestations, treatments, and neuropsychological findings are discussed.     

Cortical malformations and epilepsy

Brain malformations, resulting from aberrant patterns of brain development, are highly correlated with childhood seizure syndromes, as well as with cognitive disabilities and other neurological disorders. The structural malformations, often referred to as cortical dysplasia, are extremely varied, reflecting diverse underlying processes and critical timing of the developmental aberration. Recent studies have revealed a genetic basis for many forms of dysplasia. Gene mutations responsible for such common forms of dysplasia as lissencephaly and tuberous sclerosis have been identified, and investigators are beginning to understand how these gene mutations interrupt and/or misdirect the normal developmental pattern. Laboratory investigations, using animal models of cortical dysplasia, are beginning to elucidate how these structural malformations give rise to epilepsy and other functional pathologies.     

脑电图判读对癫痫诊断和治疗的影响

脑电图(EEG)是癫痫诊断中最重要的实验室检查方法,对确定癫痫类型,合理选择抗癫痫药物发挥了重要作用。但由于EEG操作不规范,对EEG结果不适当或错误的判读和解释,以及临床医生缺乏对EEG临床应用的理解,导致将很多非癫痫性事件误诊为癫痫,或对已经长期控制发作的癫痫病人过度治疗,由此带来一系列的医疗和社会问题。这些现象在国内外均普遍存在,应引起相关学科的高度重视。应强调规范的EEG记录,提高对EEG的判读水平,并对神经科、儿科或癫痫专科医生进行必有的EEG培训,以更好的发挥EEG在癫痫诊治中的作用。     

Serotonin in autism and pediatric epilepsies

Serotonergic abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development--and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This review explores the hypothesis that an early disturbance in the serotonin system affects cortical development and the development of thalamocortical innervation, and is a potential mechanism, common to autism and pediatric epilepsies associated with cortical dysplasia. An argument is made that cortical malformation leads to abnormalities of thalamocortical connectivity, and that serotonin plays a critical role in this process. Finally, a role for altered metabolism of the serotonin precursur, tryptophan, in both epilepsy and autism is discussed.     

Review of Commercially Available Epilepsy Genetic Panels

Next generation sequencing panels have revolutionized the diagnostic approach to patients with epilepsy. There are several commercial epilepsy panels available. We assessed the list of genes tested and consent forms for epilepsy panels available at seven laboratories. The panels varied in the number of genes included (70–465 genes). In some panels, genes not currently associated with epilepsy were included (up to 4 % of panel content). The panels also included genes for lysosomal storage disorders (6–12 %), congenital disorders of glycosylation (0–8.5 %), metabolic disorders (3.5–34 %), neurological syndromes (18–43 %) and multisystemic genetic syndromes (6.4–21 %). Informed consents differed significantly between laboratories ranging from basic information about genetic testing and possible results to information about insurance, genetic counseling and familial testing, and incidental findings.Our findings suggest that it is important to consider the range of genes offered on epilepsy panels and their predicted phenotypes in an effort toward improving the informed consent process.     

A Systematic Review of Psychiatric and Psychosocial Comorbidities of Genetic Generalised Epilepsies (GGE)

Psychiatric disorders and associated poor psychosocial outcomes are recognised to be a common sequelae of epilepsy. The extent to which this is true of genetic generalised epilepsies (GGE), particularly syndromes other than juvenile myoclonic epilepsy (JME) is unclear. This systematic review synthesises findings regarding psychiatric and associated comorbidities in adults and children with GGE. Systematic review yielded 34 peer-reviewed studies of psychiatric and psychosocial outcomes in adults and children with GGE. Clinically significant psychiatric comorbidity was reported in over half of all children and up to a third of all adults with GGE. There was no evidence to support the presence of personality traits specific to JME or other syndromes; rather rates mirrored community samples. A small number of studies report poor psychosocial outcomes in GGE, however the interpretation of these findings is limited by paucity of healthy comparison groups. Some evidence suggests that anti-epileptic drug polytherapy in children and seizure burden at all ages may constitute risk factors for psychopathology. Findings highlight the importance of early screening so as not to overlook early or developing symptoms of psychopathology.     

The debt of neuropsychology to the epilepsies.

Both neuropsychology and psychology in general have been enhanced markedly by brain-behavior models derived from the study of the epilepsies. A significant body of neuropsychological concepts originated or were confirmed through epilepsy-based treatment and research. These concepts include the peri-Rolandic homunculus, the role of the hippocampal-temporal lobe complex in cognitive memory, hemisphere plasticity for speech in childhood, the intracarotid amytal procedure for determining hemisphere memory patency, and hemisphere-based models of cognition confirmed through human commissurotomy. Personality and social-emotional research in epilepsy are additional areas in which new conceptual models grounded in psychological science can both repay our debt to the epilepsies and provide much needed psychological research and treatment.     

Genetics of neuronal migration in the cerebral cortex

The development of the cerebral cortex requires large-scale movement of neurons from areas of proliferation to areas of differentiation and adult function in the cortex proper, and the patterns of this neuronal migration are surprisingly complex. The migration of neurons is affected by several naturally occurring genetic defects in humans and mice; identification of the genes responsible for some of these conditions has recently yielded new insights into the mechanisms that regulate migration. Other key genes have been identified via the creation of induced mutations that can also cause dramatic disorders of neuronal migration. However, our understanding of the physiological and biochemical links between these genes is still relatively spotty. A number of molecules have also been studied in mice (Reelin, mDab1, and the VLDL and ApoE2 receptors) that appear to represent part of a coherent signaling pathway that regulates migration, because multiple genes cause an indistinguishable phenotype when mutated. On the other hand, two human genes that cause lissencephaly (LIS1, DCX) encode proteins that have recently been implicated as regulators or microtubule dynamics. This article reviews some of the mutant phenotypes in light of the mechanisms of neuronal migration. MRDD Research Reviews 6:34-40, 2000.     

Neuropsychological Features of Lesion-related Epilepsy in Adults: An Overview

Lesional epilepsy is thought to be a direct consequence of focal brain lesions of dysgenetic, neoplastic, vascular, or traumatic origin. It has been estimated that at least half of all epilepsies are the result of such lesions. The current discussion includes an overview of the cognitive and behavioral presentations in adults with epilepsy secondary to focal pathology. The neuropsychological presentation in this population is influenced by many factors, including the location and nature of the underlying lesion, seizure characteristics, the effects of treatment, and patient variables. Few studies attempt to disentangle the specific contributions of these variables to cognitive performance. However, where available studies examining the separable effects of seizure-related variables on cognitive functioning in individuals with lesional epilepsy are also reviewed. This overview includes a discussion of focal malformations of cortical and vascular development and select foreign tissue and acquired lesions.     

辩证分析兴奋性氨基酸对神经细胞的双重作用

兴奋性氨基酸（ＥＡＡｓ） 广泛分布于中枢神经系统,参与多种生理过程包括学习、记忆和伤害感受等。然而,ＥＡＡｓ 受体的过度兴奋却可引发一系列细胞事件,最终导致神经元的损伤与死亡。许多神经退行性疾病如早老性痴呆、癫痫和肌侧索硬化症等都与ＥＡＡｓ 的兴奋毒作用有关。目前的研究表明,由ＥＡＡｓ 受体过度兴奋所引发的细胞内钙超载是导致神经元死亡的最终途径     

The treatment of epilepsies with Convulsofin

The testing of Convulsofin carried out in 220 patients at 14 clinics over a period of six months confirms the international experience gained with valproic acid and sodium valproinate. The main field of application of Convulsofin according to the experience gained will again be the treatment of fits in generalised primary epilepsy for which it permits to carry out a monotherapy to a remarkable extent. The favourable effect of the preparation in photosensitivity could be confirmed. Also in generalised secondary epilepsy and in fits of partial epilepsy. Convulsofin is partly effective, so that it can recommended as a co-medication in the treatment of therapy-resistant forms of these epilepsies which are difficult to treat. Decrease in thrombocytes, transient increase in serum transaminases, gastrointestinal disorders, loss of hair and undesired increases in body-weight were the more frequently occurring side-effects.     

Psychoses in epilepsy

The heterogenous psychoses in epilepsies, caused by well known conditions, are not rare but associated with regularly a few of seizure-types not with the nature and development of attacks. Polar transitional ranks and converging courses of schizophrenic (accentuated) syndromes in epilepsies and idiopathic schizophrenias are rather frequent. Also (sub-)acute schizophrenic psychoses are corresponding to the complete palette of first and second rank symptoms (K. Schneider) of idiopathic schizophrenias. After manifestations of epilepsy these syndromes can appear at any time. It is given a profile of risks. Progressive avoidance of a. phenylaceturea, b. mixtures of antiepileptics did not put an end to psychotic syndromes: Long-term therapies with 1. Polytherapy, 2. Primidone and Phenytoin (dosedependant) as well as 3. Ethosuximide (-monotherapy) cause a disorder of feed back mechanisms, especially a disturbed regulation of vigilance and sleeping-waking-cycle and their psychological correlates. Carbamazepine and Sodium Valproate are, plasma-level-controlled of preventive antipsychotic effect. Selected neuroleptics of rather slight epileptogenic potency are of going down importance. Benzodiazepines are required mostly in prepsychotic syndromes, Lithium compounds in selected cases. There is no more alternative seizures or psychosis.     

Seizure types, epilepsy syndromes, etiology, and diagnosis

The clinical manifestation of epileptic seizures may vary widely from patient to patient, depending on the region of the brain involved. Over the centuries, many seizure classification systems have been used, and the current most widely used classification system is that of the International League Against Epilepsy (ILAE). The ILAE system divides seizures into those of partial onset and those of generalized onset, depending on whether the initial clinical manifestations indicate that one cortical region or both hemispheres are involved at the onset of the seizure. Partial seizures are then divided into simple partial seizures, in which a fully conscious state is retained, or complex partial seizures, in which consciousness is impaired. A more recent classification system based purely on symptom features and signs has been proposed, and this system may provide advantages for localization, and especially for surgical evaluation. Epilepsy is a condition characterized by recurrent unprovoked seizures. Epilepsy may be idiopathic, cryptogenic, or symptomatic. Idiopathic epilepsies are generally genetic, and while many such syndromes have been described, advances in molecular genetics will undoubtedly reveal many more syndromes in the near future. Cryptogenic epilepsies are those in which an underlying cause is suspected, but the etiology remains undetected. Epilepsies for which there is an underlying structural cause or major metabolic derangement are considered symptomatic. Common causes and diagnostic evaluation are described in this article.     

Molecular Genetic Studies of Eating Disorders: Current Status and Future Directions

ABSTRACT— We review association studies that have examined the genetic basis of eating disorders. Overall, findings suggest that serotonin, brain-derived neurotrophic factor, and estrogen genes may be important for the development of the disorders. These neuronal systems influence behavioral and personality characteristics (e.g., anxiety, food intake) that are disrupted in eating disorders. Future studies would benefit from larger sample sizes and inclusion of behavioral and personality covariates in analyses. Consideration of the mechanisms of genetic effects and interactions between genes and environment is also needed to extend conceptualizations of the genetic basis of these disorders.     

Possible uses of Convulsofin liquid in the treatment of pediatric epilepsies

The effect of Convulsofin-liquidum on several epilepsies and types of seizure in childhood is described. Typical and atypical absences, tonic-clonic seizures of primary generalised epilepsies as well as atonic or myoclonic seizures are considered to be the main indications for the treatment with Convulsofin. To the special advantage of the application in drops especially with infants is referred.     

On the possibility of universal neural coding of subjective experience

Various neurophysiological experiments have revealed remarkable correlations between cortical neuronal activity and subjective experiences. However, the mere presence of neuronal electrical activity does not appear to be sufficient to produce these experiences. It has been suggested that the explanation for the neural basis of consciousness might lie in understanding the reason that some types of neuronal activity possess subjective correlates and others do not. Here I propose and develop the idea that this difference may be caused by the existence of an elementary nonarbitrary linkage between temporal or spatiotemporal patterns of neuronal activity and their subjective attributes. I also show how cortical neural circuits capable of generating experience-coding patterns could emerge during evolution and brain development, due to the presence of spontaneous stochastic neuronal activity and activity-dependent synaptic plasticity. This hypothesis leads to several testable predictions, principal among which is the idea that the neural correlates of consciousness are essentially innate and universal.     

In defense of experience-coding nonarbitrary temporal neural activity patterns

Various neurophysiological experiments have revealed remarkable correlations between cortical neuronal activity and subjective experiences. However, the mere presence of neuronal electrical activity does not appear to be sufficient to produce these experiences. It has been suggested that the explanation for the neural basis of consciousness might lie in understanding the reason that some types of neuronal activity possess subjective correlates and others do not. Here I propose and develop the idea that this difference may be caused by the existence of an elementary nonarbitrary linkage between temporal or spatiotemporal patterns of neuronal activity and their subjective attributes. I also show how cortical neural circuits capable of generating experience-coding patterns could emerge during evolution and brain development, due to the presence of spontaneous stochastic neuronal activity and activity-dependent synaptic plasticity. This hypothesis leads to several testable predictions, principal among which is the idea that the neural correlates of consciousness are essentially innate and universal.     

Plasticity of nonneuronal brain tissue: roles in developmental disorders

Neuronal and nonneuronal plasticity are both affected by environmental and experiential factors. Remodeling of existing neurons induced by such factors has been observed throughout the brain, and includes alterations in dendritic field dimensions, synaptogenesis, and synaptic morphology. The brain loci affected by these plastic neuronal changes are dependent on the type of experience and learning. Increased neurogenesis in the hippocampal dentate gyrus is a well-documented response to environmental complexity ("enrichment") and learning. Exposure to challenging experiences and learning opportunities also alters existing glial cells (i.e., astrocytes and oligodendrocytes), and up-regulates gliogenesis, in the cerebral cortex and cerebellum. Such glial plasticity often parallels neuronal remodeling in both time and place, and this enhanced morphological synergism may be important for optimizing the functional interaction between glial cells and neurons. Aberrant structural plasticity of nonneuronal elements is a contributing factor, as is aberrant neuron plasticity, to neurological and developmental disorders such as epilepsy, autism, and mental retardation (i.e., fragile X syndrome). Some of these nonneuronal pathologies include abnormal cerebral and cerebellar white matter and myelin-related proteins in autism; abnormal myelin basic protein in fragile X syndrome (FXS); and abnormal astrocytes in autism, FXS, and epilepsy. A number of recent studies demonstrate the possibility of using environmental and experiential intervention to reduce or ameliorate some of the neuronal and nonneuronal abnormalities, as well as behavioral deficits, present in these neurological and developmental disorders.