The organization of functional neurocognitive networks in focal epilepsy correlates with domain-specific cognitive performance

Understanding and diagnosing cognitive impairment in epilepsy remains a prominent challenge. New etiological models suggest that cognitive difficulties might not be directly linked to seizure activity, but are rather a manifestation of a broader brain pathology. Consequently, treating seizures is not sufficient to alleviate cognitive symptoms, highlighting the need for novel diagnostic tools. Here, we investigated whether the organization of three intrinsic, resting-state functional connectivity networks was correlated with domain-specific cognitive test performance. Using individualized EEG source reconstruction and graph theory, we examined the association between network small worldness and cognitive test performance in 23 patients with focal epilepsy and 17 healthy controls, who underwent a series of standardized pencil-and-paper and digital cognitive tests. We observed that the specific networks robustly correlated with test performance in distinct cognitive domains. Specifically, correlations were evident between the default mode network and memory in patients, the central-executive network and executive functioning in controls, and the salience network and social cognition in both groups. Interestingly, the correlations were evident in both groups, but in different domains, suggesting an alteration in these functional neurocognitive networks in focal epilepsy. The present findings highlight the potential clinical relevance of functional brain network dysfunction in cognitive impairment.Peer reviewe

Epidemiology of epilepsy in Buskerud County: emphasasing clinical and psychosocial aspects of juvenile myoclonic epilepsy

Epilepsy is one of the most common neurological disorders, affecting people of all ages. Among epilepsies starting in youth, juvenile myoclonic epilepsy (JME) is the most common. The cause of JME is unknown, but it is thought to involve neuronal networks within the frontal lobes, networks which are important to decision-making and adaptation of behaviour. The aim of the present thesis was to assess epilepsy prevalence and aetiology in a Norwegian county, and to investigate whether there was an excess of risk-taking behaviour in a large and representative group of people with JME. The prevalence of epilepsy in Buskerud was 0.65%, and the prevalence of JME was 0.06%. People with JME had higher rates of police charges, use of illicit recreational drugs, and smoking prior to the age of 18 than a control group of people with other types of epilepsy. People with JME were more often victims of violence, and more often quitted their antiepileptic medication against medical advice. The present thesis provides evidence of a risk-taking behavioural profile in JME, supporting the hypothesis of disease-generating mechanisms involving networks within the frontal lobes. Furthermore, we found JME to be more common than previously reported, while the overall prevalence of epilepsy was comparable to that of previous studies

Epilepsy at different ages-Etiologies in a Norwegian population

The causes of epilepsy are age related, but confirmative data from population‐based studies are scarce. Our aim was to describe the typical causes of epilepsy in the different age groups of a defined population. The study was cross‐sectional, based on a review of all medical files containing a diagnostic code for epilepsy at Drammen Hospital from 1999‐2013. Drammen Hospital serves the population of Buskerud County, with 272 228 residents (as of January 1, 2014), including 1771 people with active epilepsy. This group of persons with active epilepsy was divided into different age groups with the causes of epilepsy mapped in each group. The proportion with unknown etiology ranged from 27% (age 5‐9) to 41% (age 10‐19). Structural‐metabolic epilepsy and perinatal insults were the leading causes of epilepsy in the age group 5‐9 (46%), whereas disturbances of brain development dominated in the youngest (23% in patients ≤4 years old). In the group comprising persons with epilepsy ≥60 years old, stroke was the most common cause of epilepsy (44%). Despite recent advances in research and technology, a large number of patients in all age groups (including the youngest) still have an unknown cause of epilepsy. We conclude that an effort must be made to improve the diagnostics for and understanding of the causes of epilepsy across all ages

Predictors of high school dropout, anxiety, and depression in genetic generalized epilepsy

Affective disorders are overrepresented in epilepsy, and people with epilepsy may be at risk of dropping out from school. The aim of the present study was to assess factors influencing high school dropout, anxiety, and depression in genetic generalized epilepsy (GGE). One hundred and ten people with GGE aged 19‐40 years underwent a clinical interview, including the Hospital Anxiety and Depression Scale (HADS) questionnaire. Potential predictors of high school dropout were analyzed with logistic regression, and factors influencing total HADS score were analyzed with linear regression. Having felt excluded because of epilepsy was significantly associated with high school dropout (odds ratio 7.80, P = .009), as was total HADS score (odds ratio 1.22, P = .005). If a participant was currently employed or undergoing education, previous high school dropout was less likely (odds ratio 0.07, P = .005). High school dropout was associated with increased current anxiety and depression (β = 0.32, P = .005). Epilepsy severity (current drug resistance, current polytherapy, and active generalized tonic‐clonic seizures) was not associated with high school dropout, nor with total HADS score. The issue of stigma in epilepsy must be thoroughly addressed in comprehensive care and may be as important as seizure control when it comes to education and quality of life

Long-term follow-up with therapeutic drug monitoring of antiepileptic drugs in patients with juvenile myoclonic epilepsy

Background and purpose: Patients with juvenile myoclonus epilepsy (JME) may experience uncontrolled seizures and challenges regarding adherence. Implementation of therapeutic drug monitoring (TDM) may contribute to individualization of the therapy with antiepileptic drugs (AEDs). The purpose of this study was to investigate how the treatment of patientswith JMEis monitored and todemonstrate pharmacokinetic variability withinand between patients with a long-term TDM approach. Method: Retrospective data from patients with JME from the TDM-database at Drammen Hospital and the National Center for Epilepsy in Norway (2007–2018) were included. Results: Data from 80 of 90 patients with JME using AEDs with TDM measurements was included (88%, 49/31 women/men aged 14–39). One third (27, 33%) was seizure free, 19 (24%) had generalized tonic-clonic seizures, and 53 (66%) myoclonic seizures during the last year. The most common AEDs measured included lamotrigine, valproate, and levetiracetam. Long-term TDM demonstrated variability over time expressed as intra-patient median values and inter-patient ranges of 19% (7–47) for valproate, 43% (10–83) for lamotrigine and 35% (6–111) forlevetiracetam. Fifteenpecent (83/563) ofserum concentrations were below the referencerangesand clould be due to variable adherence. Comedication with valproate for lamotrigine and pregnancy contributed to variability. The applicability is illustrated in a case of 10 years’ follow-up in a young woman. Conclusion: There was extensive pharmacokinetic variability of AEDs in and between patients with JME. A longterm TDM approach may contribute to closer monitoring of patients with JME and be used as a practical tool during clinical consultations

Treatment and challenges with antiepileptic drugs in patients with juvenile myoclonic epilepsy

Background: Patients with juvenile myoclonic epilepsy (JME) may have uncontrolled seizures. The purpose of this study was to investigate the use and challenges with antiepileptic drugs (AEDs) and the patients' view of these challenges. Method: A questionnaire about the use of AEDs, adherence to therapy, and quality of life was given to patients with JME recruited from Drammen Hospital. Data regarding AEDs were confirmed from medical records at Drammen Hospital, Norway (2007–2018). Additional clinical interviews were performed, and a mixed method approach was applied. Results: Ninety patients with defined JME diagnosis, 54/36 women/men aged 14–39 (mean: 25) years, were included. Only 29 (33%) were seizure-free.Within the last year, 21% experienced generalized tonic–clonic seizures (GTCS), and 68% hadmyoclonic jerks. Seventy-six (84%) used AEDs, 78% inmonotherapy. A total of 10 AEDswere used;: most commonly valproate (n = 33), lamotrigine (n = 27), and levetiracetam (n = 21). Two-thirds of valproate users were men while all other AEDs were used more in females than in men. Valproate and levetiracetam displayed better efficacy against GTCS than lamotrigine. One-third often/sometimes forgot their medication nonintentionally while 14% had intentional poor adherence. The majority reported good quality of life (76%). No significant correlations between the use of AEDs, use of valproate, poor adherence, quality of life score, and seizure freedom were demonstrated. Half of the patients had serum concentrations measured every year, and two thirds thought this was important. Qualitative interviews elucidated treatment challenges in JME;, adverse effect burden, adherence, and activities of daily life. Conclusion: Despite the use of AEDs in the majority of patients, only one-thirdwere seizure-free. Other challenges included polypharmacy, the use of valproate in women, and variable adherence. This points to a need for closer follow-up in patients with JME