In this review we systematically assess our currently available knowledge about psychogenic non-epileptic seizures (PNES) with an emphasis on the psychological mechanisms that underlie PNES, possibilities for psychological treatment as well as prognosis. Relevant studies were identified by searching the electronic databases. Case reports were not considered. 93 papers were identified; 65 of which were studies. An open non-randomized design, comparing patients with PNES to patients with epilepsy is the dominant design. A working definition for PNES is proposed. With respect to psychological etiology, a heterogeneous set of factors have been identified. Not all factors have a similar impact, though. On the basis of this review we propose a model with several factors that may interact in both the development and prolongation of PNES. These factors involve psychological etiology, vulnerability, shaping, as well as triggering and prolongation factors. A necessary first step of intervention in patients with PNES seems to be explaining the diagnosis with care. Although the evidence for the efficacy of additional treatment strategies is limited, variants of cognitive (behavioural) therapy showed to be the preferred type of treatment for most patients. The exact choice of treatment should be based on individual differences in the underlying factors. Outcome can be measured in terms of seizure occurrence (frequency, severity), but other measures might be of greater importance for the patient. Prognosis is unclear but studies consistently report that 1/3rd to 1/4th of the patients become chronic.

, a cluster of cases of pneumonia of unknown etiology were reported linked to a market in Wuhan, China 1. The causative agent was identified as the species Severe acute respiratory syndrome-related coronavirus and was named SARS-CoV-2 (ref. 2). By 16 April the virus had spread to 185 different countries, infected over 2,000,000 people and resulted in over 130,000 deaths 3. In the Netherlands, the first case of SARS-CoV-2 was notified on 27 February. The outbreak started with several different introductory events from Italy, Austria, Germany and France followed by local amplification in, and later also outside, the south of the Netherlands. The combination of near to real-time whole-genome sequence analysis and epidemiology resulted in reliable assessments of the extent of SARS-CoV-2 transmission in the community, facilitating early decision-making to control local transmission of SARS-CoV-2 in the Netherlands. We demonstrate how these data were generated and analyzed, and how SARS-CoV-2 whole-genome sequencing, in combination with epidemiological data, was used to inform public health decision-making in the Netherlands. Whole-genome sequencing (WGS) is a powerful tool to understand the transmission dynamics of outbreaks and inform outbreak control decisions 4-7. Evidence of this was seen during the 2014-2016 West African Ebola outbreak when real-time WGS was used to help public health decision-making, a strategy dubbed 'precision public health pathogen genomics' 8,9. Immediate sharing and analysis of data during outbreaks is now recommended as an integral part of outbreak response 10-12. Feasibility of real-time WGS requires access to sequence platforms that provide reliable sequences, access to metadata for interpretation, and data analysis at high speed and low cost. Therefore, WGS for outbreak support is an active area of research. Nanopore sequencing has been employed in recent outbreaks of Usutu, Ebola, Zika and yellow fever virus owing to the ease of use and relatively low start-up cost 4-7. The robustness of this method has recently been validated using Usutu virus 13,14. In the Netherlands, the first COVID-19 case was confirmed on 27 February and WGS was performed in near to real-time using an amplicon-based sequencing approach. From 22 January, symptomatic travelers from countries where SARS-CoV-2 was known to circulate were routinely tested. The first case of SARS-CoV-2 infection in the Netherlands was identified on 27 February in a person with recent travel history to Italy and an additional case was identified one day later, also in a person with recent travel history to Italy. The genomes of these first two positive samples were generated and analyzed by 29 February. These two viruses clustered differently in the phylogenetic tree, confirming separate introductions (Fig. 1a). The advice to test hospitalized patients with serious respiratory infections was issued on 24 February and subsequent attempts to identify possible local transmission chains triggered testing for SARS-CoV-2 on a large scale in h...

Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.

The abnormal, strong functional connectivity in PNES patients provides a neurophysiological correlate for the underlying psychoform and somatoform dissociation mechanism where emotion can influence executive control, resulting in altered motor function (eg, seizure-like episodes).

Clinicians should consider both neurological and psychosocial factors, including the family system, when treating psychopathology in children with epilepsy.

These findings support the hypothesis that chronic localization-related epilepsy causes cognitive deficits by inducing global cerebral network changes instead of a localized disruption only. Whether this is the result of epilepsy per se or the use of antiepileptic drugs remains to be elucidated. For application in clinical practice, future studies should address the relevance of altered cerebral network topology in prediction of cognitive deficits and monitoring of therapeutic interventions.

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

SUMMARYPurpose: To compare the cognitive profile of newly diagnosed untreated epilepsy patients with healthy volunteers using a comprehensive neuropsychological test battery. Methods: A total of 155 untreated patients with newly diagnosed epilepsy, and no known brain pathology, were assessed before the start of treatment with antiepileptic medication. Their scores across the neuropsychological measures were compared with 87 healthy volunteers from the general population equated for age and sex. Results: After adjusting for age, sex, and education, patients with epilepsy performed significantly worse than healthy volunteers on 6 of 14 cognitive measures, particularly in the domains of memory and psychomotor speed. Cognitive performance was not related to the number of seizures, type of epilepsy, or mood. When an impairment index was calculated, 53.5% patients had a least one abnormal score [>2 standard deviations (SD) below the control mean] on the test battery compared with 20.7% of healthy volunteers. Discussion: Newly diagnosed untreated patients with epilepsy are cognitively compromised before the start of antiepileptic drug medication. The domains most affected are memory and psychomotor speed. More than one-half of the patients had at least one abnormal test score across the test battery. There were no differences in epilepsy-related or mood variables between those who demonstrated dysfunction and those that did not.