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.     

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.     

Die neuen Klassifikationen von epileptischen Anfällen und Epilepsien

In 2010 the classification and terminology committee of the International League Against Epilepsy (ILAE) presented a revised proposal for the classification of epileptic seizures and epilepsy, which is also available as a German translation. In 2016 this commission presented an operational classification of epileptic seizures and new concepts for the classification of epilepsy. The essential amendments and aspects of this new classification system in comparison to the previous classification of epileptic seizures and epilepsy are briefly summarized and exemplified by two case reports.     

Neonatal seizures: early-onset seizure syndromes and their consequences for development

The determination of the developmental consequences of seizure syndromes in the neonate is based upon a number of factors which include: understanding of the clinical and electroencephalographic (EEG) features of neonatal seizures; current theories of the mechanisms by which neonatal seizures are generated; a current classification of neonatal seizures; potential etiologic and risk factors for seizures; and therapies. In addition, different seizure types, mechanisms of generation and etiologies of cerebral dysfunction may vary with conceptional age of the infant. There are a few distinct neonatal epileptic syndromes, which are rare, have been well described: benign neonatal convulsions; benign neonatal familial convulsions; early myoclonic encephalopathy and early infantile epileptic encephalopathy. The prognosis for the first two is relatively good while the outcome for the other two with encephalopathy is catastrophic. However, the majority of neonatal seizures occur as acute, reactive events in association with a wide range of etiologic factors. These etiologic factors, as well as those of the more traditionally defined syndromes, are the main determinants of eventual developmental outcome of neonates who experience seizures. Although experimental data suggests that some epileptic seizures eventually may have physiological, histological, metabolic, or behavioral consequences, there is yet direct evidence in humans to suggest that the occurrence of seizures themselves in the neonate is the main determinant of long-term outcome.     

Classroom performance and adaptive skills in children with epilepsy

The relationships of age at onset, seizure syndrome, seizure type, and seizure frequency, respectively, to the classroom performance and adaptive skills of 131 children with epilepsy were studied. The Teacher Report Form of the Child Behavior Checklist was completed by the children's teachers. Hierarchical multiple regression analyses were conducted on ratings of academic subject areas and overall adaptive skills. Significant results were obtained for English/Language, Reading, Mathematics, overall School Performance, Learning, Happy, and Total Adaptive skills. Epilepsy syndrome and frequency of seizures were significantly related to some of these analyses, with amounts of variance accounted for ranging from 11% to 23%. Children with secondary generalized epilepsy performed significantly worse than children with other epilepsy syndromes. The results suggest that a seizure disorder associated with a diffuse or multifocal brain insult can produce problems in achievement and school adaptation as manifested on a day-to-day basis. Suggestions for future research are presented.     

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.     

Sleep disorders, epilepsy, and autism

The purpose of this review article is to describe the clinical data linking autism with sleep and epilepsy and to discuss the impact of treating sleep disorders in children with autism either with or without coexisting epileptic seizures. Studies are presented to support the view that sleep is abnormal in individuals with autistic spectrum disorders. Epilepsy and sleep have reciprocal relationships, with sleep facilitating seizures and seizures adversely affecting sleep architecture. The hypothesis put forth is that identifying and treating sleep disorders, which are potentially caused by or contributed to by autism, may impact favorably on seizure control and on daytime behavior. The article concludes with some practical suggestions for the evaluation and treatment of sleep disorders in this population of children with autism.     

Speech abnormalities in seizures: a comparison of absence and partial complex seizures

In order to determine whether speech changes are useful in differentiating seizure types, a study was done in which speech abnormalities during two distinct seizure types, partial complex and absence seizures, were compared. Speech changes noted during prolonged electroencephalographic and video monitoring were compared in 16 patients with 47 partial complex seizures and 19 patients with 95 absence seizures. Speech changes were common during both seizure types. Although some significant differences in speech patterns were noted in the two seizure types, the degree of overlap was such to preclude using speech changes alone as the sole clinical criteria in differentiating the seizures.     

Conditioning of cerebral dysrhythmia induced by Pattern Presentation and Eye Closure

Previous communications from the Epilepsy Center of the University of Wisconsin described the conditioning of certain types of sensory-induced epilepsy. These included stroboscopic-induced seizures, startle epilepsy and musicogenic epilepsy. The present communication adds two types of sensory-evoked seizures treated by conditioning techniques. These additional types are the dysrhythmias induced by pattern presentation and by eye closure. The techniques employed are similar in their main concept to those previously reported. The presentation of a noxious stimulus is altered in such a way as to be innocuous, then is presented repeatedly without producing a seizure. Next, the stimulus is altered gradually until the noxious state is reached. Although these techniques are of value in the treatment of refractory cases of sensory-evoked epilepsy, their major importance is the demonstration that it is possible by the use of behavioral techniques to alter the electroencephalogram and the neurophysiological-neurochemical state which is epilepsy.     

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。     

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.     

Structural and functional imaging in children with partial epilepsy

Imaging plays an increasingly important role in the evaluation of children with complex partial seizures. Most partial epilepsy, especially of temporal lobe origin, begins during childhood. Structural imaging with high-resolution MRI can help identify the etiology of partial seizure disorders in many children. MRI studies also show the more widespread effect of seizures on brain structure. Progressive volume loss of the hippocampal formation in some patients with temporal lobe epilepsy provides evidence that continued seizures may be associated with progressive neuronal injury. FDG-PET studies show regional decreases in glucose consumption in the cortical zone from which seizures arise. Functional abnormalities often are more extensive than the seizure focus. Studies in children with recent-onset epilepsy show that metabolic abnormalities are considerably less common than in adults with partial epilepsy, supporting the notion that in some patients there may be progressive metabolic changes that occur with continued seizures. Functional MRI may be used to identify language areas in children with partial epilepsy. fMRI language tasks reliably identify the dominant hemisphere for language dominance when compared to the intracarotid amytal procedure. Tests of verbal fluency and semantic decision identify frontal lobe language areas, while reading text paradigms and auditory passage paradigms are better for identifying temporal language areas. A panel of paradigms is best used to identify language areas in children being considered for epilepsy surgery. fMRI is a valuable tool for elucidating the impact of chronic neurologic disease states on the functional organization of language networks during development.     

Drug treatment of epilepsy: when does it fail and how to optimize its use?

Although modern community-based studies have shown that a majority of people with newly diagnosed epilepsy will enter long-term remission, seizures remain refractory to treatment in a substantial proportion of this population--perhaps as much as 40%. A consensus is being reached that, for operational purposes, pharmacoresistance can be suspected when two appropriately chosen, well-tolerated, first-line antiepileptic drugs (AEDs) or one monotherapy and one combination regimen have failed due to lack of efficacy. Poor prognostic factors include lack of response to the first AED, specific syndromes, symptomatic etiology, family history of epilepsy, psychiatric comorbidity, and high frequency of seizures. These observations suggest that prognosis can often be determined early in the course of the disorder. We propose a management paradigm that aims to maximize the chance of successful AED therapy, including the early use of "rational polytherapy" for patients not responding to monotherapy, and to identify efficiently patients suitable for "curative" resective surgery, in particular those with mesial temporal lobe epilepsy. An orderly approach to each epilepsy syndrome will optimize the chance of perfect seizure control and help more patients achieve a fulfilling life.     

Massively multiplayer online role-playing game-induced seizures: a neglected health problem in Internet addiction.

As the Internet has become rapidly and widely integrated into society, Internet addiction has become a growing psychosocial problem. However, epileptic seizure, another out-of-the-ordinary health problem, is often neglected in this regard. Ten patients who experienced epileptic seizures while playing the newest genre of electronic games -- Massively Multiplayer Online Role-Playing Games (MMORPGs) -- were investigated. Patients were predominantly male young adults, and most of the events were generalized tonic-clonic seizures, myoclonic seizures, and absences. These patients should be categorized into idiopathic generalized epilepsies. Even though photosensitivity was an important factor, behavioral and higher mental activities also seemed to be significant seizure precipitants. Results demonstrated that MMORPG-induced seizures were not analogous to the ordinary video game-induced seizures. Significantly, an epileptic seizure warning did not always appear on the websites of MMORPGs and instructions for the software. While the prevalence of MMORPG-induced seizures remains unknown, it may exceed our expectations and impact our society. Not only for clinical neurologists but also for the primary physicians, educators, sociologists, and global online game publishers, there should be an awareness of this special form of reflex seizures in order to provide an appropriate health warning to MMORPG players.     

Significance of the EEG for the prognosis of therapy in adult epileptic patients

The importance of EEG findings regarding prognosis of therapy and relapses of epilepsies is controversally discussed in the literature. On the basis of 495 patients being in attendance for many years there were some important indications for prognosis, for instance 59 percent of the patients with normal EEG at all times during the cours attained freedom from seizures for at least five years. The best possibilities for differentiation followed from EEG features during medication, especially from degree od disturbances of background activity. Only 13 percent of patients with more than slight disturbances in resting EEG remained seizure free for a long time. Also as a distinctly unfavourable sign proved the combination of generalized and focal epileptiform pattern.     

The default mode network and altered consciousness in epilepsy

The default mode network has been hypothesized based on the observation that specific regions of the brain are consistently activated during the resting state and deactivated during engagement with task. The primary nodes of this network, which typically include the precuneus/posterior cingulate, the medial frontal and lateral parietal cortices, are thought to be involved in introspective and social cognitive functions. Interestingly, this same network has been shown to be selectively impaired during epileptic seizures associated with loss of consciousness. Using a wide range of neuroimaging and electrophysiological modalities, decreased activity in the default mode network has been confirmed during complex partial, generalized tonic-clonic, and absence seizures. In this review we will discuss these three seizure types and will focus on possible mechanisms by which decreased default mode network activity occurs. Although the specific mechanisms of onset and propagation differ considerably across these seizure types, we propose that the resulting loss of consciousness in all three types of seizures is due to active inhibition of subcortical arousal systems that normally maintain default mode network activity in the awake state. Further, we suggest that these findings support a general "network inhibition hypothesis", by which active inhibition of arousal systems by seizures in certain cortical regions leads to cortical deactivation in other cortical areas. This may represent a push-pull mechanism similar to that seen operating between cortical networks under normal conditions.     

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.     

Comparison of auras and triggering factors in epilepsy

Case reports of five patients are presented, each with a specific aura at the onset of the seizures. All of these patients’ had seizures during the waking state. Their auras were carefully replicated and presented to the patients under various conditions. The presentation of the auras evoked neither clinical nor EEG evidence of seizures. A sixth patient had seizures only when asleep which were preceded by vivid nightmares. Since the seizures occurred only when the patient was asleep, we considered that the seizures could be reflex in nature and evoked by a dream. Replication of the dream, however, did not evoke clinical or EEG evidence of epilepsy. The dreams, therefore, were auras or a part of the seizure complex.     

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.