Risk factors for status epilepticus after brain disorders in adults: A multi-cohort national register study.

PURPOSE: We aimed to describe risks of status epilepticus (SE) after different brain disorders in adults using population-wide register data. Our hypothesis was that SE would be more common in disorders with widespread pathology and that the risk would increase with disorder severity. METHODS: We analyzed five large datasets created from the Swedish National Patient Register, the Cause of Death Register, and national quality registers with adults in Sweden with brain infections, dementia, multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Risk factors were assessed using Cox regression. RESULTS: In adults with TBI, stroke, dementia, MS, or brain infections, the incidence rate of SE was highest in survivors of brain infections (64/100,000 person years) and stroke (64/100,000), followed by TBI (37/100,000), dementia (36/100,000), and MS (26/100,000). SE was considerably more common in patients with epilepsy after their brain disorder. Across all datasets severe disorder increased SE-risk. Herpes simplex encephalitis (HR 5.5 95 % CI: 2.6-12), progressive MS (HR 2.3, 95 % CI: 1.1-4.7), structural TBI (2.0, 95 % CI: 1.6-2.6), and intracerebral hemorrhage (HR 1.5, 95 % CI: 1.2-2.0) were the subtypes of brain disorders with the highest relative risk of SE. Having another CNS disorder increased SE-risk in TBI (HR 2.9, 95 % CI: 2.3-3.7), brain infections (HR 2.8, 95 % CI: 1.7-4.5), and dementia (HR 2.5, 95 % CI: 1.5-4.2). CONCLUSION: SE-risk increases with disorder severity and number of CNS comorbidities. These findings can guide treatment strategy by allowing identification of high-risk patients. Pathophysiological studies are needed to better understand remote symptomatic SE.

Second antiseizure medication monotherapy in patients with adult-onset epilepsy: A register-based analysis.

OBJECTIVE: Revision of therapy is fundamental in epilepsy care, since only half of patients achieve seizure freedom and tolerate the first antiseizure medication (ASM). We studied the selection and retention of second antiseizure medication monotherapy in adults who discontinued treatment with one of the three most frequently prescribed first ASMs, and the impact of age or brain comorbidities. METHODS: Using Swedish national registers, we conducted a population-based, retrospective cohort study from 2007 to 2019 on patients age ≥ 30 at the epilepsy diagnosis that had switched to a second monotherapy after the three most common initial monotherapies (n = 7369). Retention rates (RR) were estimated via Kaplan-Meier. Discontinuation of the second monotherapy was defined as 12-month prescription gap or initiation of a third ASM. Analyses were stratified by sex, age, and presence of stroke or dementia. RESULTS: The three most commonly prescribed second ASMs were carbamazepine, levetiracetam, and lamotrigine. The 1-year retention rate was 63-76% in all patients. For groups with stroke or dementia, the maximal 1-year RRs were 77% and 87%, respectively. After five years, retention rates ranged from 12% to 39%. There were no major differences between ASMs, apart from in patients discontinuing carbamazepine, where lamotrigine had a superior retention compared to levetiracetam as second monotherapy. SIGNIFICANCE: The three most often prescribed second ASMs seem to be suitable treatment options according to present guidelines. The second ASMs' retention rates were initially high in all studied patient groups but dropped to approximately the expected proportion of second monotherapy responders over the next five years. This suggests that therapy revision could be expedited.

Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population-based cohort study.

OBJECTIVE: Historically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real-world data. Third-generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden. METHODS: A multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy. RESULTS: A total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52-77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow-up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty-nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p = .010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16-3.51). SIGNIFICANCE: Levetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow-up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.

Neurofilament light, glial fibrillary acidic protein, and tau in a regional epilepsy cohort: High plasma levels are rare but related to seizures.

OBJECTIVE: Higher levels of biochemical blood markers of brain injury have been described immediately after tonic-clonic seizures and in drug-resistant epilepsy, but the levels of such markers in epilepsy in general have not been well characterized. We analyzed neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau in a regional hospital-based epilepsy cohort and investigated what proportion of patients have levels suggesting brain injury, and whether certain epilepsy features are associated with high levels. METHODS: Biomarker levels were measured in 204 patients with an epilepsy diagnosis participating in a prospective regional biobank study, with age and sex distribution correlating closely to that of all patients seen for epilepsy in the health care region. Absolute biomarker levels were assessed between two patient groups: patients reporting seizures within the 2 months preceding inclusion and patients who did not have seizures for more than 1 year. We also assessed the proportion of patients with above-normal levels of NfL. RESULTS: NfL and GFAP, but not tau, increased with age. Twenty-seven patients had abnormally high levels of NfL. Factors associated with such levels were recent seizures (p = .010) and epileptogenic lesion on radiology (p = .001). Levels of NfL (p = .006) and GFAP (p = .032) were significantly higher in young patients (<65 years) with seizures ≤2 months before inclusion compared to those who reported no seizures for >1 year. NfL and GFAP correlated weakly with the number of days since last seizure (NfL: rs = -.228, p = .007; GFAP: rs = -.167, p = .048) in young patients. NfL also correlated weakly with seizure frequency in the last 2 months (rs = .162, p = .047). SIGNIFICANCE: Most patients with epilepsy do not have biochemical evidence of brain injury. The association with seizures merits further study; future studies should aim for longitudinal sampling and examine whether individual variations in NfL or GFAP levels could reflect seizure activity.

Risk of poststroke epilepsy after reperfusion therapies: A national cohort study.

BACKGROUND AND PURPOSE: The risk of poststroke epilepsy (PSE) after endovascular treatment (EVT) is not well characterized. In this nationwide study, we assessed the risk of PSE after EVT and identified associated predictors. METHODS: We included all individuals (n = 3319) treated with EVT (±intravenous thrombolysis [IVT]) between 2015 and 2019 in the Swedish National Quality Register for EVT. Two control groups were identified from the Swedish Stroke Register: the first treated with IVT alone (n = 3132) and the second with no treatment (n = 3184), both matched for age, sex, stroke severity, and time of stroke. RESULTS: PSE developed in 7.9% (n = 410). The survival-adjusted 2-year risk was 6.5% (95% confidence interval [CI] = 5.28-7.70) after EVT, 10.0% (95% CI = 8.25-11.75) after IVT, and 12.3% after no revascularization (95% CI = 10.33-14.25). The hazard ratio (HR) of PSE after EVT was almost half compared to no treatment (HR = 0.51, 95% CI = 0.41-0.64). The risk of PSE after EVT was lower compared to no treatment in a multivariable Cox model that adjusted for age, sex, hemicraniectomy, and stroke severity (HR = 0.76, 95% CI = 0.60-0.96). Multivariable predictors of PSE after EVT were large infarction on computed tomography Day 1, high posttreatment National Institutes of Health Stroke Scale score, and need of assistance 3 months after stroke. IVT before EVT was associated with a lower risk of PSE (HR = 0.66, 95% CI = 0.46-0.94). CONCLUSIONS: This nationwide study identified a reduced risk of PSE after EVT. Markers of severe infarction after EVT were associated with PSE, whereas IVT given before EVT was protective.

Presence of neural surface and onconeural autoantibodies in cerebrospinal fluid and serum in neurological diseases presents a potential risk for misdiagnosis.

BACKGROUND AND PURPOSE: Autoantibodies have been found to contribute to pathology and are used in the diagnosis of some neurological diseases. We examined the prevalence of autoantibodies in patients with various neurological diseases and whether patients who had autoantibodies differed in age, sex, or disability from those who did not. METHODS: We examined the prevalence of neural surface and onconeural autoantibodies in cerebrospinal fluid (CSF) and serum from patients with multiple sclerosis (n = 64), Parkinson disease plus atypical parkinsonism (n = 150), amyotrophic lateral sclerosis (n = 43), or autoimmune encephalitis (positive control; n = 7) and a healthy control group (n = 37). A total of 12 onconeural autoantibodies and six neural surface autoantibodies were tested in all participants. RESULTS: Autoantibodies were present in all cohorts. The prevalence of autoantibodies was high (>80%) in the autoimmune encephalitis cohort but low (<20%) in all other cohorts. When comparing patients within cohorts who were positive for autoantibodies to patients who were not, there was no difference in age, sex, and disability. This was apart from the multiple sclerosis and Parkinson disease plus atypical parkinsonism cohorts, where those with positivity for autoantibodies in the CSF were significantly older. CONCLUSIONS: The presence of the autoantibodies examined does not appear to have a substantial clinical impact within the diseases examined in this study. The presence of autoantibodies in all cohorts presents a risk for misdiagnosis when the method is used incorrectly on patients with atypical clinical presentation.

Big data analysis of ASM retention rates and expert ASM algorithm: A comparative study.

OBJECTIVE: Only 50% of patients with new-onset epilepsy achieve seizure freedom with their first antiseizure medication (ASM). A growing body of data illustrates the complexity of predicting ASM response and tolerability, which is influenced by age, sex, and comorbidities. Randomized data with sufficient resolution for personalized medicine are unlikely to emerge. Two potential facilitators of ASM selection are big data using real-world retention rates or algorithms based on expert opinion. We asked how these methods compare in adult-onset focal epilepsy. METHODS: ASM retention rates were determined by cross-referencing data from comprehensive Swedish registers for 37 643 individuals, with identified comorbidities. Eight fictive cases were created and expert advice was collected from the algorithm Epipick. We compared Epipick suggestions in representative patient subgroups, and determined whether ranking based on retention rate reflected expert advice. RESULTS: The Epipick algorithm suggested six ASM alternatives for younger patients and three ASM alternatives for older patients. In the real-world data, retention rates for the ASMs ranked as best options by Epipick were high; 65%-72% for young patients and 71%-84% for older patients. The lowest retention rate for Epipick suggestions was 42%-56% in younger cases, and 70%-80% in older cases. The ASM with the best retention rate was generally recommended by Epipick. SIGNIFICANCE: We found a large overlap between expert advice and real-world retention rates. Notably, Epipick did suggest some ASMs with more modest retention rates. Conversely, clearly inappropriate ASMs (not recommended by Epipick) had high retention rates in some cases, showing that decision systems should not rely indiscriminately on retention rates alone. In future clinical decision support systems, expert opinion and real-world retention rates could work synergistically.

Valproate Restrictions in Sweden and Norway: Online survey suggests implementation deficit.

OBJECTIVES: To assess knowledge among neurologists in Sweden and Norway on the restrictions issued by the European Medicines Agency (EMA) regarding use of valproic acid (VPA) to female patients of childbearing potential, their use of the pregnancy prevention programme and their VPA prescription habits. MATERIALS & METHODS: We conducted an online survey from May through September 2021 inviting neurologists in Sweden and Norway to participate. The questions assessed familiarity with the EMA restrictions, knowledge and use of the information material issued by Market Authorization Holders (MAH) of VPA, and experience of VPA prescriptions to women of childbearing age in the last 2 years. RESULTS: The survey received 202 responses (response rate ≈ 20%). Of the responders, 51% were well acquainted with the EMA restrictions, and 49% were aware of the MAH-issued educational material. Eighty-eight (44%) had prescribed VPA to women of childbearing age in the last 2 years, and of these, only a small minority (n = 13) regularly used the information brochure for patients, and even fewer (n = 8) the VPA risk acknowledgement forms. CONCLUSIONS: We found limited penetrance of the new EMA restrictions on VPA use as well as limited acceptance and use among prescribers of the current company-issued information material and risk acknowledgment forms. More information campaigns and closer collaboration with treating physicians are likely needed.

Blood biomarkers in epilepsy.

Robust and accessible biomarkers are greatly needed in epilepsy. Diagnostic and prognostic precision in the clinic needs to improve, and there is a need for objective quantification of seizure burden. In recent years, there have been advances in the development of accessible and cost-effective blood-based biomarkers in neurology, and these are increasingly studied in epilepsy. However, the field is in its infancy and specificity and sensitivity for most biomarkers in most clinical situations are not known. This review describes advancements regarding human blood biomarkers in epilepsy. Examples of biochemical markers that have been shown to have higher blood concentrations in study subjects with epilepsy include brain proteins like S100B or neuronal specific enolase, and neuroinflammatory proteins like interleukins, and tumor necrosis factor-alpha. Some of the blood biomarkers also seem to reflect seizure duration or frequency, and levels decrease in response to treatment with antiseizure medication. For most biomarkers, the literature contains seemingly conflicting results. This is to be expected in an emerging field and could reflect different study populations, sampling or analysis techniques, and epilepsy classification. More studies are needed with emphasis put on the classification of epilepsy and seizure types. More standardized reporting could perhaps decrease result heterogeneity and increase the potential for data sharing and subgroup analyses.

Temporal trends of epilepsy in multiple sclerosis.

OBJECTIVES: Epilepsy is associated with advanced multiple sclerosis (MS). We aimed to investigate whether the incidence of epilepsy in MS has been affected by the introduction of disease-modifying treatments (DMT) for MS. MATERIALS AND METHODS: This retrospective study included 14,557 patients from the Swedish MS register with MS onset between 1991 and 2018. Incident diagnoses of epilepsy or any seizure were identified through cross-linkage with the National Patient Register. Next, yearly prevalence of epilepsy as well as 5- and 10 years incidence of epilepsy or any seizure for consecutive years of MS onset were estimated, the latter with Kaplan-Meier analysis. Cox regression was used to adjust the association between the year of MS onset and incidence of epilepsy for baseline variables. RESULTS: Prevalence of epilepsy in the MS cohort increased from 0.34% in 1991 to 2.54% in 2018 (yearly odds: 1.26 [1.22, 1.29]). The 5 years incidence rate of epilepsy, ranging from 0.4% (95% CI 0.008-0.79%) to 1.3% (95% CI 0.71-1.89%), and the 10 years incidence rate of epilepsy, ranging from 1.1% (95% CI 0.31-1.88%) to 2.6% (95% CI 1.22-3.97%) showed no significant trends (p = .147 and p = .418, respectively). Similarly, no significant trends were found for the incidences of any seizure. The incidence trends of epilepsy remained not significant after adjusting for sex, MS onset type (relapsing or progressive onset), or age at MS onset. CONCLUSIONS: Our findings do not support the hypothesis that the introduction of novel DMT for MS has reduced the incidence of epilepsy among MS patients.

Perceived stigma in adults with epilepsy in Sweden and associations with country of birth, socioeconomic status, and mental health.

BACKGROUND: Stigma contributes to negative health outcomes and amplifies health disparities in epilepsy. This study aimed to investigate associations of perceived stigma with the country of birth and socioeconomic status (SES). METHODS: This is a cross-sectional questionnaire study. Participants were recruited consecutively from three demographically different neurology outpatient clinics in the southwest of Sweden. Participants responded to a questionnaire concerning their epilepsy, country of birth, mother tongue, and different SES-variables. The Neuro-QOL stigma scale and the Jacoby stigma scale were applied to assess stigma and the Hospital Anxiety and Depression Scale (HADS) and PROMIS Mental Health scale were applied to assess mental health. RESULTS: In total 161 adults with epilepsy were included in the cohort. The median Neuro-QOL stigma score was 48.3, and was higher among foreign-born than in native-born participants (foreign-born in non-European country 52.3, in other European country 49.8, and in native-born 47.0, p = 0.003). Other factors associated with Neuro-QOL were seizure frequency last year (≥2 seizures 52.4 compared to 1 seizure 50.9 and no seizures 44.3, p < 0.001), having had seizures in public (yes 50.9 compared to no 44.7, p = 0.035), HADS depression score ≥11 (57.4 compared to 47.8 for score <11 points, p < 0.001), HADS anxiety score ≥11 (53.5 compared to 46.8 for score <11 points, p < 0.001), and lower PROMIS Mental Health score (42.9 for PROMIS < 40 compared to 54.4 for PROMIS > 60, p < 0.01). A stepwise multiple regression analysis indicated that having had seizures the last year increased the average Neuro-QOL stigma score with 5.89 and appeared as the most determining factor for the Neuro-QOL stigma score among the variables investigated. CONCLUSIONS: It is important that the concerns of foreign-born patients are acknowledged and that the focus of seizure control and the detection and treatment of comorbidities are prioritized in the management of epilepsy and perceived stigma.

Pediatric Ischemic Stroke and Epilepsy: A Nationwide Cohort Study.

Background and Purpose: The risk of epilepsy after stroke has not been thoroughly explored in pediatric ischemic stroke. We examined the risk of epilepsy in children with ischemic stroke as well as in their first-degree relatives. Methods: In Swedish National Registers, we identified 1220 children <18 years with pediatric ischemic stroke diagnosed 1969 to 2016, alive 7 days after stroke and with no prior epilepsy. We used 12 155 age- and sex-matched individuals as comparators. All first-degree relatives to index individuals and comparators were also identified. The risk of epilepsy was estimated in children with ischemic stroke and in their first-degree relatives using Cox proportional hazard regression model. Results: Through this nationwide population-based study, 219 (18.0%) children with ischemic stroke and 91 (0.7%) comparators were diagnosed with epilepsy during follow-up corresponding to a 27.8-fold increased risk of future epilepsy (95% CI, 21.5­36.0). The risk of epilepsy was still elevated after 20 years (hazard ratio [HR], 7.9 [95% CI, 3.3­19.0]), although the highest HR was seen in the first 6 months (HR, 119.4 [95% CI, 48.0­297.4]). The overall incidence rate of epilepsy was 27.0 per 100 000 person-years (95% CI, 21.1­32.8) after ischemic stroke diagnosed ≤day 28 after birth (perinatal) and 11.6 per 100 000 person-years (95% CI, 9.6­13.5) after ischemic stroke diagnosed ≥day 29 after birth (childhood). Siblings and parents, but not offspring, to children with ischemic stroke were at increased risk of epilepsy (siblings: HR, 1.64 [95% CI, 1.08­2.48] and parents: HR, 1.41 [95% CI, 1.01­1.98]). Conclusions: The risk of epilepsy after ischemic stroke in children is increased, especially after perinatal ischemic stroke. The risk of epilepsy was highest during the first 6 months but remained elevated even 20 years after stroke which should be taken into account in future planning for children affected by stroke.

Post-traumatic epilepsy in adults: a nationwide register-based study.

OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of epilepsy. Our aim was to characterise the risk of epilepsy in adults after hospitalisation for TBI. METHODS: Register-based cohort study. All individuals aged 18-100 with a first hospitalisation for TBI in the comprehensive national patient register in Sweden between 2000 and 2010 (n=111 947) and three controls per exposed (n=325 881), matched on age and sex were included. Exposed individuals were categorised according to TBI severity. Kaplan-Meier curves were used to estimate the risk of epilepsy and Cox regression to estimate the hazard in univariate or multivariate regression. RESULTS: The 10-year risk of epilepsy was 12.9% (95% CI 11.7% to 14.1%) for focal cerebral injuries, 8.1% (95% CI 7.5% to 8.7%) for diffuse cerebral injuries, 7.3% (95% CI 6.9% to 7.7%) for extracerebral injuries, 2.8% (95% CI 2.4% to 3.2%) for skull fractures and 2.6% (95% CI 2.4% to 2.8%) for mild TBI. The risk of epilepsy after any TBI was 4.0% (95% CI 3.8% to 4.2%). The corresponding 10-year risk for controls was 0.9% (95% CI 0.9% to 0.9%). The HR increased with a more severe injury, from 3.0 (95% CI 2.8 to 3.2) for mild injury to 16.0 (95% CI 14.5 to 17.5) for focal cerebral injury. Multivariable analyses identified central nervous system (CNS) comorbidities as risk factors, but TBI remained significant also after adjustment for these. Other identified risk factors were male sex, age, mechanical ventilation and seizure during index hospitalisation. CONCLUSION: The risk of post-traumatic epilepsy is considerable, also with adjustments for CNS comorbidities.

Prehospital lactate levels in blood as a seizure biomarker: A multi-center observational study.

OBJECTIVE: The objective of this study was to assess the value of prehospital measurement of lactate level in blood for diagnosis of seizures in cases of transient loss of consciousness. METHODS: Between March 2018 and September 2019, prehospital lactate was measured with a point-of-care device by the emergency medical services in an area serving a population of 900 000. A total of 383 cases of transient loss of consciousness were identified and categorized as tonic-clonic seizure (TCS), other seizure, syncope, or other cause, according to the final diagnosis in the electronic medical records system. Receiver operating characteristic curve analyses were used to identify the optimal lactate cut-off. RESULTS: A total of 383 cases were included (135 TCS, 42 other seizure, 163 syncope, and 43 other causes). The median lactate level in TCS was 7.0 mmol/L, compared to a median of 2.0 mmol/L in all other cases (P < .001). The area under the curve (AUC) of TCS vs nonepileptic causes was 0.87 (95% confidence interval [CI] 0.83-0.91). The optimal cut-off (Youden index, 67.8%) was 4.75 mmol/L, with 79% sensitivity (95% CI 71-85) and 89% specificity (95% CI 85-93) for TCS. SIGNIFICANCE: Prehospital lactate can be a valuable tool for identifying seizures in transient loss of consciousness. For acceptable specificity, a higher cut-off than that previously demonstrated for hospital-based measurements must be used when values obtained close to the time of the event are interpreted.

Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis.

OBJECTIVE: The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. METHODS: We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. RESULTS: Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). SIGNIFICANCE: We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.

Long-term seizure and psychosocial outcome in childhood epilepsy of unknown cause.

OBJECTIVE: The purpose was to investigate long-term prognosis of epilepsy of unknown cause with onset between ages 2 and 16 in children without any major disability, by evaluation of a previously described prognostic model and long-term follow-up of a study on the impact of duration of initial antiseizure medication (ASM) treatment. METHODS: Patients included in a randomized controlled trial (RCT) of either one or three years of ASM therapy prior to withdrawal (if seizure-free for at least 6 months) were contacted after 29-35 years and asked to complete a survey. Potential prognostic factors were evaluated: duration of initial ASM treatment, seizure type, seizure frequency, and score in a prognostic model developed in the initial publication. RESULTS: One hundred and forty-nine subjects answered the questionnaire (response rate 65%). Seizure freedom without treatment was found in 110 responders (77%, 95%CI: 73-81). There was no significant difference in score in the prognostic model between responders with and without epilepsy at follow-up. Those with active epilepsy were unemployed significantly more often and perceived their mental health significantly more affected than those seizure-free without treatment. CONCLUSIONS: Duration of initial ASM treatment was not associated with any difference in subsequent epilepsy risk. This indicates that the timing of withdrawal attempts is unlikely to alter the long-term prognosis of uncomplicated childhood epilepsy. The failure of the prognostic model from the initial study to predict long-term outcome argues that although prediction of relapse risk in the shorter term may be possible, the bearing of such models on long-term epilepsy risk is more questionable.

Valproic acid and socioeconomic associations in Swedish women with epilepsy 2010-2015.

OBJECTIVE: We investigated the correlation between socioeconomic status and the prescription of Valproic acid (VPA) in women of fertile age in Sweden. METHODS: This is a registered-based cohort study including all women living in Sweden aged 18-45 years in the years 2010-2015, with a diagnosis of epilepsy and no intellectual disability (n = 9143). Data were collected from the National Patient Register, the Drug Prescription Register, and the Longitudinal integration database for health insurance and labor market studies (LISA). RESULTS: Women with only 9 years of school were more often prescribed VPA than women with a University degree (12.9% compared to 10.7% in 2015 [p = 0.015]). Similar differences were seen between the lowest and highest income group (16.6% compared to 12.7% in 2015 [p < 0.001]). The odds of having a VPA prescription in 2015 was 1.59 (p < 0.001) in women with 9 years of school compared to women with a University degree, and 1.60 (p < 0.001) in the lowest income group relative to the highest income group after adjusting for age. From 2010 to 2015, the proportion with VPA prescription in the whole cohort diminished with an absolute reduction of -2.2% (p < 0.001). The decrease was similar among the different education and income groups (p = 0.919 and p = 0.280). SIGNIFICANCE: The results indicate that the increased knowledge on VPA teratogenicity was implemented across socioeconomic strata in the Swedish healthcare system. Women with lower income or education level remained more frequent VPA users. Whether this difference reflects epilepsy type or severity, or socioeconomic disparities, merit further study.

Retention of antiseizure medications for epilepsy in multiple sclerosis: A retrospective observational study.

PURPOSE: Epilepsy in multiple sclerosis (MS) is rare, and longitudinal clinical studies evaluating treatment with antiseizure medications (ASMs) are difficult to conduct. We instead designed a nationwide register study to estimate retention rates of ASMs prescribed as initial monotherapy for epilepsy in MS and investigated factors influencing their retention. METHODS: multiple sclerosis patients with a first prescription of ASM for epilepsy were identified by cross-referencing the Swedish MS register with comprehensive national registers. One and five-year retention rates of ASMs were estimated using Kaplan-Meier analysis. Cox proportional regression was employed to estimate hazard ratios (HR) of discontinuation for different ASMs as well as for baseline predictors. RESULTS: One hundred and twenty-nine MS patients were included. The most commonly prescribed ASMs were: carbamazepine (n = 38, 29.5%), lamotrigine (n = 33, 25.6%) and levetiracetam (n = 19, 14.7%). One-year retention rates (95% CI) were: lamotrigine 87.5% [76, 98.9], carbamazepine 60.5% [45, 76], levetiracetam 60.2% [37.2, 83.2], valproate 51.3% [23, 79.6] and phenytoin 44.4% [11.8, 77]. Fiveyear retention rates (95% CI) were: lamotrigine 74.4% [57.3, 91.5], carbamazepine 52.2% [34.9, 69.4], valproate 51.3% [23.1, 79.5] and phenytoin 14.8% [0, 40.9]. With carbamazepine as reference, lamotrigine was the only ASM that displayed a lower hazard of discontinuation, HR 0.41 [0.17, 0.99]. We could not identify any baseline factors that influenced the risk of discontinuation. CONCLUSION: Lamotrigine displayed the lowest risk of discontinuation when prescribed as initial monotherapy for epilepsy in MS. Newer ASMs generally compared well to older ones, at least suggesting non-inferiority.

Multiple stigma among first-generation immigrants with epilepsy in Sweden.

OBJECTIVES: To investigate the meaning of stigma among first-generation immigrants with epilepsy in Sweden. METHODS: Data were collected by individual face-to-face interviews with 25 first-generation immigrants with epilepsy from 18 different countries. Interviews were recorded, transcribed verbatim, and analyzed systematically using a hermeneutic approach. RESULTS: Multiple aspects of stigma were associated with epilepsy, immigration, and socioeconomic deprivation. The main theme "It is a fight to be appreciated as a person and member of society" illuminated the meaning of stigma in the struggle with a negative self-image and strategies to build self-confidence. The seizure-related fears were amplified by language barriers and a lack of knowledge of the healthcare system that obstructed access to health care. Few close relatives nearby or misconceptions of epilepsy in the family resulted in a lack of support. The stigma of being an immigrant and of socioeconomic deprivation resulted in feelings of being unvalued by the society in addition to feelings of being unvalued in relationships and at work because of epilepsy. The social isolation experienced as a result of immigration was increased due to the presence of perceived stigma due to epilepsy which led people to stay at home in order to conceal their epilepsy. At the same time, to inform others about their epilepsy could reduce seizure-related fears. Employment appeared as a symbol of being a capable person and helped participants gain self-confidence. CONCLUSIONS: Barriers to access health care and the exposure to multiple stigma can result in increased seizure-related fears, social isolation, and a lack of support for immigrants with epilepsy. In the context of epilepsy and immigration, stigma was intricately connected to how people perceived themselves as capable and contributing members of society. To reduce the negative influence of stigma, employment appeared vital to build self-confidence and break social isolation. Investigating the patient's experience of stigma may provide healthcare professionals with valuable information on the need for support and priorities in epilepsy management. Public efforts to increase knowledge about epilepsy also among first-generation immigrants would be valuable.

Randomized controlled trial of moderate cardiovascular exercise for patients with drug-resistant epilepsy.

OBJECTIVE: The primary research question of this study was whether a moderate cardiovascular exercise program can reduce seizure frequency in patients with focal drug-resistant epilepsy (DRE). The hypothesis is that cardiovascular fitness will reduce seizure frequency in persons with epilepsy (PWE). METHODS: Twenty-eight patients were randomized into two groups; exercise or relaxation. The exercise group were given an ergometric bicycle sent to their home to be used for 150 min/week, 30 min/day for 5 days a week for the study period of 6 months. Participants in the relaxation group were given audio muscular relaxation exercises to be performed for 20 min at least five times per week for the study period of 6 months. Seizure counts and exercise/relaxation sessions were registered daily in a written diary. Both groups received monthly motivational telephone calls. Seizures, anxiety, and depression symptom ratings (Hospital Anxiety and Depression Scale (HADS)), health status ratings (RAND-36), aerobic capacity (estimated VO2max), self-efficacy for exercise (SEE), level of physical activity, and adverse events were measured at the baseline and after the 6 months of intervention. CONSORT guidelines were followed. RESULTS: Twenty-two patients completed the intervention. There were no significant changes in seizure frequency in either of the groups. Six months of moderate exercise did increase the level of physical activity and maximal oxygen uptake. SIGNIFICANCE: Moderate exercise did not affect seizure frequency in this study. The patients in the exercise group did increase their estimated VO2max, which is an important indicator for health, without deterioration of seizure frequency. This was accomplished with only minimal support from a physiotherapist every month. To exercise at home at a moderate intensity level with regular support may therefore be an option for patients with epilepsy. The patients in the exercise group increased their level of physical activity significantly, which indicates that they were compliant to the treatment.