Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and Autism

A high proportion of children with epilepsy have autism spectrum disorder. Although estimates vary, depending both on the population studied and the definitions used, a figure of around 20% has typically been reported. Autism can have a major impact on the life of the child and family. Despite the importance of this comorbidity and although many studies have been performed, a full understanding of the possible links between epilepsy and autism remains elusive. In a minority of cases, for example in the Landau‐Kleffner syndrome, the autistic features can be the result of the epilepsy itself. However, there has been a failure to demonstrate that the epilepsy itself plays a major role in most cases. The current evidence seems to point to a common underlying predisposing factor. The discovery of a growing number of genetic defects leading to both conditions would support this explanation of the link.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and ADHD

ADHD occurs in about 30% of children with epilepsy. The causes of ADHD features include some antiepileptic drugs, the epilepsy itself and underlying brain dysfunction. Management of the ADHD will depend on the cause. Treatment with methylphenidate is effective in about 70% of cases; standard treatments with methylphenidate, dexamfetamine and atomoxetine are very unlikely to exacerbate seizures.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Behavioural effects of epilepsy surgery

There are relatively few studies of the behavioural outcome of epilepsy surgery in children that have used standardised behavioural measures before and after the procedure. Those investigations that have used such measures are often on mixed groups with mixed pathology, implying that the numbers, when stratified, are very small. They are also often retrospective. Furthermore, because placebo surgery is generally not an option, the studies have been open and they are usually uncontrolled. The few available data suggest that, although individual children may benefit or deteriorate, there is little overall group effect of temporal or extratemporal surgery on behavioural/psychiatric outcome. Hemispherectomy has traditionally been associated with the expectation of marked behavioural improvement but firm data are lacking. Multiple subpial transection performed for electrical status epilepticus of slow‐wave sleep in the Landau‐Kleffner syndrome can result in marked improvements in cognition and behaviour. Vagus nerve stimulation appears to improve quality of life and mood/behaviour but again the quality of the data has been questioned. There is a need for large, prospective, multicentre, collaborative studies using standardised cognitive and behavioural measures before and after surgery to provide an adequate database on the outcome of various categories of procedures, pathologies and patients.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epidemiology of psychiatric/behavioural disorder in children with epilepsy

Psychiatric/behavioural problems can have a major effect on quality of life. Epidemiological studies in Europe, Scandinavia and the USA have confirmed a high rate of psychiatric disorder in children with epilepsy, typically around 35 to 50%. In children with additional impairment, particularly those with intellectual disability, the rates are even higher, over 50%. Determining the causes of these high rates and deciding on the best strategies, either for prevention or for optimal management, remain major challenges.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Anxiety,depression and childhood epilepsy

Anxiety and depression are relatively common in children with epilepsy: anxiety has been reported in 15–36% and depression in 8–35% of patients. In some cases these conditions may be related specifically to the epilepsy or its treatment. For example, some antiepileptic drugs are known to be associated with depression in adults and are likely to have a similar effect in young people. Emotional reactions to the epilepsy, for example anxieties and social phobia related specifically to the seizures, might be expected and require appropriate management. However, there is a growing recognition of the bidirectional relationship between epilepsy and psychiatric disorders, including depression, largely based on adult data. Cognitive behavioural therapy and serotonin reuptake inhibitors are used for treatment of both anxiety and depression in children with epilepsy. There is a need for greater understanding of the causes of these conditions in young people and there is also a need for better evidence for optimal treatment.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Adverse cognitive and behavioural effects of antiepileptic drugs in children

The literature was evaluated for cognitive and more general behavioural effects. We distinguished the older antiepileptic drugs (AEDs), from the newer and newest AEDs. The striking finding was the lack of information on children. From the available evidence it would appear that there may be negative cognitive effects with phenobarbital, phenytoin, topiramate and zonisamide, and adverse behavioural effects with phenobarbital, valproate, gabapentin, topiramate, levetiracetam and zonisamide. There is inconclusive data on ethosuximide, clobazam, vigabatrin, felbamate, pregabalin, stiripentol, rufinamide, lacosamide and retigabine. The following drugs appear to be neutral with regard to cognitive effects: valproate, carbamazepine, gabapentin and oxcarbazepine. Carbamazepine appears to be neutral with regard to behavioural effects. Positive cognitive effects have been reported with lamotrigine and levetiracetam. Positive behavioural effects have been reported with lamotrigine. Recommendations are provided.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Epilepsy and psychosis in children and teenagers

Psychosis related to epilepsy or antiepileptic treatment can occur in teenagers and very rarely in children. Postictal, interictal and antiepileptic‐drug‐induced psychosis have all been reported in young people. Whether ictal psychosis occurs in this age group remains open to debate. Neuronal antibody encephalitis such as anti‐NMDA receptor encephalitis can present with seizures and psychosis, both of which can resolve with prompt, appropriate immunotherapy. In addition, there have been several reports in which the terms psychosis or psychotic features have been used loosely to describe behavioural disturbance in children with epilepsy; in these cases there have apparently been no diagnostic features of psychosis, implying that these terms should not have been used. The management of epilepsy‐related psychosis in young people is similar to that in adults. Antipsychotic medication should not be withheld if it is needed on clinical grounds. If the psychosis has been induced by antiepileptic medication then a medication review is necessary.     

Establishing criteria for pediatric epilepsy surgery center levels of care: Report from the ILAE Pediatric Epilepsy Surgery Task Force

Presurgical evaluation and surgery in the pediatric age group are unique in challenges related to caring for the very young, range of etiologies, choice of appropriate investigations, and surgical procedures. Accepted standards that define the criteria for levels of presurgical evaluation and epilepsy surgery care do not exist. Through a modified Delphi process involving 61 centers with experience in pediatric epilepsy surgery across 20 countries, including low–middle- to high-income countries, we established consensus for two levels of care. Levels were based on age, etiology, complexity of presurgical evaluation, and surgical procedure. Competencies were assigned to the levels of care relating to personnel, technology, and facilities. Criteria were established when consensus was reached (≥75% agreement). Level 1 care consists of children age 9 years and older, with discrete lesions including hippocampal sclerosis, undergoing lobectomy or lesionectomy, preferably on the cerebral convexity and not close to eloquent cortex, by a team including a pediatric epileptologist, pediatric neurosurgeon, and pediatric neuroradiologist with access to video-electroencephalography and 1.5-T magnetic resonance imaging (MRI). Level 2 care, also encompassing Level 1 care, occurs across the age span and range of etiologies (including tuberous sclerosis complex, Sturge-Weber syndrome, hypothalamic hamartoma) associated with MRI lesions that may be ill-defined, multilobar, hemispheric, or multifocal, and includes children with normal MRI or foci in/abutting eloquent cortex. Available Level 2 technologies includes 3-T MRI, other advanced magnetic resonance technology including functional MRI and diffusion tensor imaging (tractography), positron emission tomography and/or single photon emission computed tomography, source localization with electroencephalography or magnetoencephalography, and the ability to perform intra- or extraoperative invasive monitoring and functional mapping, by a large multidisciplinary team with pediatric expertise in epilepsy, neurophysiology, neuroradiology, epilepsy neurosurgery, neuropsychology, anesthesia, neurocritical care, psychiatry, and nursing. Levels of care will improve safety and outcomes for pediatric epilepsy surgery and provide standards for personnel and technology to achieve these levels.     

Development of cognitive functions in children with rolandic epilepsy

An initial investigation of cognitive functions in 32 children, aged 7 to 15 years, with rolandic epilepsy (RE), using an extensive test battery, was followed 2.5 to 3 years later by a second assessment of 26 of these children, using the same technique. The initial investigation reported cognitive deficits in memory and learning of auditory-verbal material together with executive functions compared with controls. At the second assessment, the ability for immediate memory, memory and learning of visuospatial as well as auditory-verbal material and delayed recall was the same in the RE group as in the control group. On one of the tests measuring executive functions, Verbal Fluency, the RE group scored significantly lower than controls. With respect to reading and writing ability, the children with RE had some difficulty with word comprehension. Nonverbal reasoning was the same in the two groups, as was general IQ. In conclusion, the children with RE did not present any major cognitive difficulties when a mean of approximately 5 years had passed since onset of the typical syndrome, and at a time when most of them were seizure-free. Maturational factors apparently are of importance to the course of RE.     

Deficit of endogenous spatial orienting of attention in children with benign epilepsy with centrotemporal spikes (BECTS)

Attention difficulties have been reported in children with benign epilepsy with centrotemporal spikes (BECTS) but have not yet been fully specified. The aim of this study was to evaluate the functions of exogenous and endogenous spatial orienting of attention and alerting in these children. Two versions of the spatial cueing paradigm and an alerting task, including trials with and without warning signal, were performed by 25 children with BECTS aged 6–12 years and 25 controls matched for age, gender and IQ. In these three tasks, patients were slower and made more omissions than controls. The alert effect amplitude was comparable in both groups at the longer SOAs (450 ms and 800 ms) while, at the shortest SOA (100 ms), it was greater in controls than in the BECTS group. In the first version of the spatial cueing task (peripheral cues and no probability information), the validity effect amplitude, measured by longer response times (RTs) in invalid trials compared to valid trials, was comparable in both groups. In the second version (central cues and a 75% probability that the target would appear at the cued location), the validity effect was larger in the BECTS group compared to controls because of a higher cost of invalid trials compared to neutral trials. These results suggest the existence of impairments in the endogenous orienting of attention in children with BECTS, in particular an attention disengagement deficit, while exogenous orienting of attention appears to be preserved.     

Management of epilepsy in older adults: A critical review by the ILAE Task Force on Epilepsy in the elderly

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.     

Technical aspects of pediatric epilepsy surgery: Report of a multicenter,multinational web‐based survey by the ILAE Task Force on Pediatric Epilepsy Surgery

Surgical techniques may vary extensively between centers. We report on a web‐based survey aimed at evaluating the current technical approaches in different centers around the world performing epilepsy surgery in children. The intention of the survey was to establish technical standards. A request was made to 88 centers to complete a web‐based survey comprising 51 questions. There were 14 questions related to general issues, 13 questions investigating the different technical aspects for children undergoing epilepsy surgery, and 24 questions investigating surgical strategies in pediatric epilepsy surgery. Fifty‐two centers covering a wide geographic representation completed the questionnaire. The median number of resective procedures per center per year was 47. Some important technical practices appeared (>80% of the responses) such as the use of prophylactic antibiotics (98%), the use of high‐speed drills for bone opening (88%), nonresorbable material for bone flap closure (85%), head fixation (90%), use of the surgical microscope (100%), and of free bone flaps. Other questions, such as the use of drains, electrocorticography (ECoG) and preoperative withdrawal of valproate, led to mixed, inconclusive results. Complications were noted in 3.8% of the patients submitted to cortical resection, 9.9% hemispheric surgery, 5% callosotomy, 1.8% depth electrode implantation, 5.9% subdural grids implantation, 11.9% hypothalamic hamartoma resection, 0.9% vagus nerve stimulation (VNS), and 0.5% deep brain stimulation. There were no major differences across regions or countries in any of the subitems above. The present data offer the first overview of the technical aspects of pediatric epilepsy surgery worldwide. Surprisingly, there seem to be more similarities than differences. That aside many of the evaluated issues should be examined by adequately designed multicenter randomized controlled trials (RCTs). Further knowledge on these technical issues might lead to increased standardization and lower costs in the future, as well as definitive practice guidelines.     

Spatial and temporal dynamics of epileptic activity at sleep onset in the Encephalopathy with Status Epilepticus during slow sleep (ESES) after unilateral thalamic lesions

ObjectiveEncephalopathy with Status Epilepticus during slow Sleep (ESES) is a syndrome where neurocognitive impairment correlates with multifocal Electroencephalography (EEG) spikes increasing abruptly at sleep onset. Demonstration of a focal onset could provide important clues to unravel the mechanisms underlying the condition, but until know it has not been established.MethodsWe studied epileptic dynamics at sleep onset to assess its focal or diffuse features in five patients with perinatal thalamic hemorrhages lateralized to one hemisphere, using high resolution EEG.ResultsDynamical functional connectivity revealed the information flow in the epileptic network and identified primary sources of outflow, equated with cortical spike sources. We found that spikes with important activation originate in restricted cortical areas of the hemisphere with the lesion, spreading widely and quickly at onset of N2 sleep stage.ConclusionsPerinatal thalamic lesions have the potential to induce, years later, a regional onset of epileptic activity with features of ESES in a cortex without apparent structural lesion. Most widespread spike activity in the scalp results from secondary propagation.SignificancePerinatal thalamic lesions produce ESES with focal onset in a restricted cortical area of the hemisphere with the lesion, and prominent secondary propagation.     

Big data in epilepsy: Clinical and research considerations. Report from the Epilepsy Big Data Task Force of the International League Against Epilepsy

Epilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities. Modern computing firepower and advances in machine and deep learning, pioneered in other diseases, open up exciting possibilities for epilepsy too. However, without carefully designed approaches to acquiring, standardizing, curating, and making available such data, there is a risk of failure. Thus, careful construction of relevant ontologies, with intimate stakeholder inputs, provides the requisite scaffolding for more ambitious big data undertakings, such as an epilepsy data commons. In this review, we assess the clinical and research epilepsy landscapes in the big data arena, current challenges, and future directions, and make the case for a systematic approach to epilepsy big data.     

Brief Report: Impaired Flexible Item Selection Task (FIST) in School-Age Children with Autism Spectrum Disorders

Cognitive flexibility has been measured with inductive reasoning or explicit rule tasks in individuals with autism spectrum disorders (ASD). The Flexible Item Selection Task (FIST) differs from previous cognitive flexibility tasks in ASD research by giving children an abstract, ambiguous rule to switch. The ASD group (N = 22; Mean age = 8.28 years, SD = 1.52) achieved a lower shift percentage than the typically developing verbal mental-age control group (N = 22; Mean age = 6.26 years, SD = 0.82). There was a significant positive correlation between verbal mental age and shift percentage for children with ASD. Group differences on the FIST converge and extend prior evidence documenting an impaired ability to adapt rapidly to changes in task demands for individuals with ASD.