SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy.

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

Variation in prognosis and treatment outcome in juvenile myoclonic epilepsy: a Biology of Juvenile Myoclonic Epilepsy Consortium proposal for a practical definition and stratified medicine classifications.

Reliable definitions, classifications and prognostic models are the cornerstones of stratified medicine, but none of the current classifications systems in epilepsy address prognostic or outcome issues. Although heterogeneity is widely acknowledged within epilepsy syndromes, the significance of variation in electroclinical features, comorbidities and treatment response, as they relate to diagnostic and prognostic purposes, has not been explored. In this paper, we aim to provide an evidence-based definition of juvenile myoclonic epilepsy showing that with a predefined and limited set of mandatory features, variation in juvenile myoclonic epilepsy phenotype can be exploited for prognostic purposes. Our study is based on clinical data collected by the Biology of Juvenile Myoclonic Epilepsy Consortium augmented by literature data. We review prognosis research on mortality and seizure remission, predictors of antiseizure medication resistance and selected adverse drug events to valproate, levetiracetam and lamotrigine. Based on our analysis, a simplified set of diagnostic criteria for juvenile myoclonic epilepsy includes the following: (i) myoclonic jerks as mandatory seizure type; (ii) a circadian timing for myoclonia not mandatory for the diagnosis of juvenile myoclonic epilepsy; (iii) age of onset ranging from 6 to 40 years; (iv) generalized EEG abnormalities; and (v) intelligence conforming to population distribution. We find sufficient evidence to propose a predictive model of antiseizure medication resistance that emphasises (i) absence seizures as the strongest stratifying factor with regard to antiseizure medication resistance or seizure freedom for both sexes and (ii) sex as a major stratifying factor, revealing elevated odds of antiseizure medication resistance that correlates to self-report of catamenial and stress-related factors including sleep deprivation. In women, there are reduced odds of antiseizure medication resistance associated with EEG-measured or self-reported photosensitivity. In conclusion, by applying a simplified set of criteria to define phenotypic variations of juvenile myoclonic epilepsy, our paper proposes an evidence-based definition and prognostic stratification of juvenile myoclonic epilepsy. Further studies in existing data sets of individual patient data would be helpful to replicate our findings, and prospective studies in inception cohorts will contribute to validate them in real-world practice for juvenile myoclonic epilepsy management.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

Monogenic developmental and epileptic encephalopathies of infancy and childhood, a population cohort from Norway.

Introduction: Developmental and epileptic encephalopathies (DEE) is a group of epilepsies where the epileptic activity, seizures and the underlying neurobiology contributes to cognitive and behavioral impairments. Uncovering the causes of DEE is important in order to develop guidelines for treatment and follow-up. The aim of the present study was to describe the clinical picture and to identify genetic causes in a patient cohort with DEE without known etiology, from a Norwegian regional hospital. Methods: Systematic searches of medical records were performed at Drammen Hospital, Vestre Viken Health Trust, to identify patients with epilepsy in the period 1999-2018. Medical records were reviewed to identify patients with DEE of unknown cause. In 2018, patients were also recruited consecutively from treating physicians. All patients underwent thorough clinical evaluation and updated genetic diagnostic analyses. Results: Fifty-five of 2,225 patients with epilepsy had DEE of unknown etiology. Disease-causing genetic variants were found in 15/33 (45%) included patients. Three had potentially treatable metabolic disorders (SLC2A1, COQ4 and SLC6A8). Developmental comorbidity was higher in the group with a genetic diagnosis, compared to those who remained undiagnosed. Five novel variants in known genes were found, and the patient phenotypes are described. Conclusion: The results from this study illustrate the importance of performing updated genetic investigations and/or analyses in patients with DEE of unknown etiology. A genetic cause was identified in 45% of the patients, and three of these patients had potentially treatable conditions where available targeted therapy may improve patient outcome.

Sex-specific disease modifiers in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.

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.

Source-level EEG and graph theory reveal widespread functional network alterations in focal epilepsy.

OBJECTIVE: The hypersynchronous neuronal activity associated with epilepsy causes widespread functional network disruptions extending beyond the epileptogenic zone. This altered network topology is considered a mediator for non-seizure symptoms, such as cognitive impairment. The aim of this study was to investigate functional network alterations in focal epilepsy patients with good seizure control and high quality of life. METHODS: We compared twenty-two focal epilepsy patients and sixteen healthy controls on graph metrics derived from functional connectivity of source-level resting-state EEG. Graph metrics were calculated over a range of network densities in five frequency bands. RESULTS: We observed a significantly increased small world index in patients relative to controls. On the local level, two left-hemisphere regions displayed a shift towards greater alpha band "hubness". The findings were not mediated by age, sex or education, nor by age of epilepsy onset, duration or focus lateralisation. CONCLUSIONS: Widespread functional network alterations are evident in focal epilepsy, even in a cohort characterised by successful anti-seizure medication therapy and high quality of life. These findings might support the position that functional network analysis could hold clinical relevance for epilepsy. SIGNIFICANCE: Focal epilepsy is accompanied by global and local functional network aberrancies which might be implied in the sustenance of non-seizure symptoms.

Trait impulsivity in Juvenile Myoclonic Epilepsy.

OBJECTIVE: Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta-analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs). METHODS: 322 participants with JME and 126 age and gender-matched controls completed the Barratt's Impulsiveness Scale (BIS-brief) alongside information on seizure history and AED use. We compared group BIS-brief scores and assessed associations of JME BIS-brief scores with seizure characteristics and AED adverse effects. RESULTS: The mean BIS-brief score in JME was 18.1 ± 4.4 compared with 16.2 ± 4.1 in controls (P = 0.0007). Elevated impulsivity was associated with male gender (P = 0.027), frequent absence seizures (P = 0.0004) and lack of morning predominance of myoclonus (P = 0.008). High impulsivity significantly increased the odds of a psychiatric adverse event on levetiracetam (P = 0.036), but not any other psychiatric or somatic adverse effects. INTERPRETATION: Trait impulsivity is elevated in JME and comparable to scores in personality and neurotic disorders. Increased seizure frequency and absence of circadian seizure pattern moderate BIS score, suggesting disruption of both cortico-striatal and thalamocortical networks as a shared mechanism between seizures and impulsivity in JME. These findings warrant consideration of impulsivity as a distinct target of intervention, and as a stratifying factor for AED treatment in JME, and perhaps other types of epilepsy. The role of impulsivity in treatment adherence and psychosocial outcome requires further investigation.

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 (ß = 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.

Trait impulsivity correlates with active myoclonic seizures in genetic generalized epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a common subtype of genetic generalized epilepsy (GGE) arising in adolescence and is often associated with executive function (EF) deficits. Some EF components like response inhibition have been extensively evaluated in JME, but few studies have focused upon trait impulsivity or compared between GGE subtypes. The aim of the present study was to compare the association of trait impulsivity in JME with other GGE subtypes. METHODS: Patients with GGE aged between 14 and 40 years (n = 137) were divided into those with JME (n = 92) and those with other GGEs (n = 45: 8 childhood absence epilepsy (CAE), 22 juvenile absence epilepsy (JAE), and 15 epilepsy with generalized tonic-clonic seizures only (EGTCS)). The study participants were recruited through medical records of the general population of Buskerud County and the neighboring municipalities, covering 477,000 people or 9.1% of Norway's total population. All participants underwent a clinical interview including the Barratt Impulsiveness Scale (BIS), an established measure of trait impulsivity. We controlled for other potential predictors of BIS score using analysis of covariance (ANCOVA). RESULTS: There were no differences between JME and other types of GGE for BIS scores, but the presence of myoclonic seizures within the last year, irrespective of GGE subtype, was independently associated with significantly increased behavioral impulsivity. CONCLUSIONS: This study demonstrates that trait impulsivity in GGE is most strongly related to the recent occurrence of myoclonic seizures rather than GGE subtype.

Meta-analysis of response inhibition in juvenile myoclonic epilepsy.

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) show evidence of cognitive impulsivity that may be linked to later adverse psychosocial outcomes. Here, we quantify the strength of association and estimate effect size (ES) of response inhibition by pooling available evidence in a meta-analysis. METHODS: We conducted a systematic review of the literature using Ovid MEDLINE and Ovid EMBASE databases (covering 2001-2019) with a search strategy using combinations of the specific Medical Subject Headings (MeSH) terms 'juvenile myoclonic epilepsy, cognitive impulsivity, response inhibition, Stroop, cognition, personality, traits' using the 'explode' feature where possible. We also searched within references of retrieved articles. We included studies reporting ESs describing established measures of response inhibition in teenage and adult patients with JME. RESULTS: Using the ESs pooled from 16 studies comprising 1047 patients and controls, we found ESs for response inhibition to be homogeneous with a significant moderate mean ES of d = 0.50 (95% confidence interval [CI]: 0.37-0.63). CONCLUSIONS: We confirm that reduced response inhibition is a consistently observed homogeneous trait in patients with JME.

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% had myoclonic jerks. Seventy-six (84%) used AEDs, 78% in monotherapy. A total of 10 AEDs were 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-third were 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.

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 patients with JME is monitored and to demonstrate pharmacokinetic variability within and 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) for levetiracetam. Fifteen pecent (83/563) of serum concentrations were below the reference ranges and 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 long-term TDM approach may contribute to closer monitoring of patients with JME and be used as a practical tool during clinical consultations.

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.

Antiepileptic drug withdrawal in juvenile myoclonic epilepsy.

OBJECTIVES: Withdrawal of antiepileptic drugs (AEDs) has been discouraged in juvenile myoclonic epilepsy (JME). However, impulsivity as a consequence of executive dysfunction in JME may influence treatment adherence. The aim of the present study was to assess how common withdrawal of AEDs is in a large and representative JME group. MATERIALS AND METHODS: Patients with genetic generalized epilepsy (GGE) were identified through a retrospective search of medical records at Drammen Hospital, Norway, and invited to a clinical interview. Information related to AED withdrawal was analyzed in those classified as JME. RESULTS: A total of 132 patients with GGE were interviewed (87 JME). Thirty-five patients with JME (40%) discontinued AEDs, of which 74% did so without consulting a doctor. The rate of self-withdrawal was significantly higher in JME than in other types of GGE. Having a parent with psychosocial difficulties was significantly over-represented in the JME self-withdrawal group. Twelve of those who discontinued AEDs (34%) were free from generalized tonic-clonic seizures (GTCS) and without antiepileptic drugs >1 year. All but one of them withdrew AEDs without consulting a doctor. Age at first motor seizure was significantly higher in those with a favorable outcome of AED withdrawal. CONCLUSIONS: Self-withdrawal of AEDs is common in JME, especially in those with troublesome conditions at home. However, about 1/3 may remain free from GTCS without AEDs. The findings indicate a need for a stronger follow-up with appropriate information about the prognosis of the disorder.

Psychosocial complications in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) constitutes about 10% of all epilepsies. Because of executive dysfunction, people with JME may be prone to impulsivity and risk-taking behavior. Our aim was to investigate whether psychosocial issues associated with impulsivity are more prominent in people with JME than in those with other types of genetic generalized epilepsy (GGE). Patients with GGE were recruited retrospectively through the Drammen Hospital records in Buskerud County, Norway, 1999-2013. They were invited to a semi-structured interview, either at the hospital or at home. Ninety-two patients with JME and 45 with other types of GGE were interviewed. Variables were evaluated in terms of their association with JME versus other GGE diagnosis using a logistic regression model. Juvenile myoclonic epilepsy was associated with use of illicit recreational drugs and police charges, although with borderline significance (odds ratio [OR] 3.4, p = 0.087 and OR 4.2, p = 0.095); JME was also associated with being examined for attention-deficit hyperactivity disorder (ADHD) in females (OR 15.5, p = 0.015), a biological parent with challenges like addiction or violent behavior (OR 3.5, p = 0.032), and use of levetiracetam (OR 5.1, p = 0.014). After controlling for group differences, we found psychosocial complications to be associated with JME, potentially influencing the lives of the individuals and their families to a greater extent than the seizures per se. Thus, JME should be considered a disorder of the brain in a broader sense than a condition with seizures only.

Prolonged epileptiform EEG runs are associated with persistent seizures in juvenile myoclonic epilepsy.

OBJECTIVE: In juvenile myoclonic epilepsy (JME), various EEG characteristics have been suggested as poor prognostic signs, but their significance is unclear. The aim of this study was to assess the influence of EEG variables on seizure and psychosocial outcome after a follow-up exceeding 20 years. METHODS: 396 EEG recordings were available for assessment in 40 patients (42 complete digital, 330 paper segments and 24 written reports only). Mean follow-up was 31 years (range 20-68). The number of EEGs per patient ranged from 2 to 23 (mean 9). Twenty-one patients were in remission for >5 years, whereas 19 had persistent seizures. Favorable psychosocial outcome was found in 14 of 37. EEGs were retrospectively categorized into four main groups; normal, slowing, epileptiform discharges or both slowing and epileptiform discharges, with further sub-classification. Hyperventilation and photoparoxysmal responses were also evaluated. Scoring of EEG findings was blinded to seizure and psychosocial outcome. RESULTS: Significant associations were found between poor seizure control and prolonged ≥3s epileptiform runs, p=0.03 (8/19 vs 2/21), long ≥3s photoparoxysmal runs, p=0.04 (6/19 vs 1/21) and long ≥3s hyperventilation-induced epileptiform runs, p=0.02 (5/19 vs 0/21). The strongest association between persistent seizures and EEG was found when all epileptiform runs ≥3s were combined (p=0.007), with a positive predictive value equal to 79% and a negative predictive value equal to 69%. Fast (4-5c/s) spike-wave runs were also more frequent in patients with persistent seizures compared to the remission group, p=0.04 (9/19 vs 3/21). Other epileptiform elements occurred equally in the two prognostic groups. Psychosocial outcome was not influenced by EEG findings. Prolonged runs within 6 months from first recording did also predict clinical outcome, p=0.03; (8/19 vs 2/21), with a positive predictive value equal to 80% and a negative predictive value equal to 63%. SIGNIFICANCE: Fast spike-wave runs and prolonged (≥3s) epileptiform runs, including photoparoxysmal and hyperventilation-induced runs were associated with persistent seizures in JME. Focal EEG abnormalities were not associated with clinical outcome. Conceivably, the duration of epileptiform bursts reflects the degree of deficient intracortical inhibition. Prolonged runs may represent an essential predictive feature for poor seizure control in JME.

Prevalence of juvenile myoclonic epilepsy in people <30 years of age-A population-based study in Norway.

OBJECTIVE: Despite juvenile myoclonic epilepsy (JME) being considered one of the most common epilepsies, population-based prevalence studies of JME are lacking. Our aim was to estimate the prevalence of JME in a Norwegian county, using updated diagnostic criteria. METHODS: This was a cross-sectional study, based on reviews of the medical records of all patients with a diagnosis of epilepsy at Drammen Hospital in the period 1999-2013. The study population consisted of 98,152 people <30 years of age. Subjects diagnosed with JME, unspecified genetic generalized epilepsy, or absence epilepsy were identified. All of these patients were contacted and asked specifically about myoclonic jerks. Electroencephalography (EEG) recordings and medical records were reevaluated for those who confirmed myoclonic jerks. Information about seizure onset was obtained from the medical records, and annual frequency of new cases was estimated. RESULTS: A total of 55 subjects fulfilled the diagnostic criteria for JME. The point prevalence was estimated at 5.6/10,000. JME constituted 9.3% of all epilepsies in the age group we investigated. Of subjects diagnosed with either unspecified genetic generalized epilepsy or absence epilepsy, 21% and 12%, respectively, had JME. We identified 21 subjects with JME (38%) who had not been diagnosed previously. Six subjects (11%) had childhood absence epilepsy evolving into JME. Between 2009 and 2013, the average frequency of JME per 100,000 people of all ages per year was estimated at 1.7. SIGNIFICANCE: A substantial portion of people with JME seem to go undiagnosed, as was the case for more than one third of the subjects in this study. By investigating subjects diagnosed with unspecified genetic generalized epilepsy or absence epilepsy, we found a prevalence of JME that was considerably higher than previously reported. We conclude that JME may go undiagnosed due to the underrecognition of myoclonic jerks. To make a correct diagnosis, clinicians need to ask specifically about myoclonic jerks.

Prevalence and incidence of epilepsy in the Nordic countries.

BACKGROUND: Updated knowledge on the prevalence of epilepsy is valuable for planning of health services to this large and complex patient group. Comprehensive epidemiological research on epilepsy has been undertaken, but because of variations in methodology, the results are difficult to compare. The objective of this article is to present evidence-based estimates of the prevalence and incidence of epilepsy in the Nordic countries. METHOD: The article is based on a search in PubMed with the search terms epilepsy and epidemiology, combined with each of the Nordic countries separately. RESULTS: Altogether 38 original articles reported incidence and/or prevalence rates of epilepsy in a Nordic country. Four studies had investigated the prevalence of active epilepsy in all age groups, with results ranging from 3.4 to 7.6 per 1,000 inhabitants. Only two studies had investigated the incidence of epilepsy in a prospective material that included all age groups. The reported incidence amounted to 33 and 34 per 100,000 person-years respectively. A prospective study that only included adults reported an incidence of 56 per 100,000 person-years. INTERPRETATION: We estimate that approximately 0.6% of the population of the Nordic countries have active epilepsy, i.e. approximately 30,000 persons in Norway. Epilepsy is thus one of the most common neurological disorders. The incidence data are more uncertain, but we may reasonably assume that 30-60 new cases occur per 100,000 person-years.