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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., (© 2022 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of Competing Interest J. Zelano reports consultancy fee from the Swedish medical products agency, the National Board of Health and Welfare and speaker honoraria from UCB and Eisai for non-branded educational events. As an employee of Sahlgrenska university hospital (no personal compensation) he is/has been investigator in clinical trials sponsored by GW pharma, Bial, SK life science, and UCB. The other authors have no disclosures to report., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of epilepsy, a disease generally associated with increased morbidity and mortality, is increased in multiple sclerosis (MS) but its impact on MS prognosis is largely unknown., Objectives: To investigate the association between acquired epilepsy and mortality in MS and to examine the occurrence of epilepsy as a stated cause of death in MS. To examine the association between acquired epilepsy and subsequent conversion to secondary progressive MS (SPMS)., Methods: Using the Swedish MS register, we conducted a nationwide register-based cohort study including 10,383 patients with MS onset between 31/12/1991 and 31/12/2014, and with no history of epilepsy before MS onset. Data on epilepsy diagnosis and cause of death (COD) were extracted from comprehensive national registers. Cox regression was used to estimate hazard ratios (HR) of death stratified by MS course, and SPMS conversion after epilepsy diagnosis. The HRs were adjusted for age at MS onset and sex., Results: The adjusted HR of death after epilepsy diagnosis for unselected MS patients was 3.85 (95% CI: 2.53-5.85). Stratifying by disease course, the adjusted HR of death after epilepsy diagnosis in primary progressive MS was 2.28 (95% CI: 0.99-5.26) and in relapsing-onset MS (ROMS), 5.48 (95% CI: 3.33-9.04). Further subdivision of ROMS revealed the adjusted risk of death after epilepsy diagnosis in relapsing remitting MS to be 3.84 (95% CI: 1.57-9.42) and 6.66 (95% CI: 3.18-13.92) in SPMS. Epilepsy was the underlying COD in 4.55% of MS patients with epilepsy. The majority (50%) of MS patients with epilepsy had MS as their stated underlying COD. Adjusted HR of conversion to SPMS after epilepsy diagnosis was 0.83 (95% CI: 0.45-1.56)., Conclusion: Epilepsy in MS is associated with increased mortality although death from epilepsy is rare. Most MS patients with epilepsy died of MS, and epilepsy was most lethal when developed in SPMS. We thus suggest that development of epilepsy is a marker of severe MS. Despite this, we found no association between epilepsy and conversion to SPMS., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: The 2014 International League Against Epilepsy clinical definition of epilepsy allows diagnosis after a single unprovoked seizure if the 10-year recurrence risk exceeds 60%. Multiple sclerosis (MS) carries an increased risk of epilepsy, but the risk after a first seizure is unknown. We aimed to investigate the risk of epilepsy in patients with MS who had suffered a first seizure., Methods: We cross-referenced data from the Swedish MS register with the national patient register for 15 810 patients with MS and 43 635 controls and included 289 patients with MS and 222 controls with a first diagnosis of seizure or status epilepticus (SE) without prior epilepsy or presumed symptomatic aetiology. Kaplan-Meier curves were used to estimate the risk of epilepsy., Results: The 10-year risk of epilepsy was 51.4% [95% confidence interval (CI), 44.0-58.9] for patients with MS and 41.3% (95% CI, 33.5-49.1) for controls. The risk was 46.1% (95% CI, 35.3-56.9) for patients with relapsing-remitting MS and 60.7% (95% CI, 46.6-74.8) for patients with secondary progressive MS. For patients with MS with SE, the 10-year risk of epilepsy was 85.9% (95% CI, 67.9-100)., Conclusions: Our data indicate that patients with relapsing-remitting MS have a similar risk as controls of developing epilepsy after a single seizure. Patients with secondary progressive MS could run a greater risk of subsequent epilepsy, but our data do not indicate a risk that, with certainty, exceeds the threshold specified by the International League Against Epilepsy. Patients with SE have a high risk of epilepsy, possibly motivating diagnosis and treatment., (© 2018 EAN.)

Purpose: The prevalence of epilepsy is increased in multiple sclerosis (MS), but information on AED treatment and seizure outcome is scarce. We describe epilepsy characteristics including the use of AEDs and proportion of seizure-free patients at two tertiary hospitals in Sweden., Method: We retrospectively studied electronic medical records of all patients with a diagnosis of MS and seizures at Sahlgrenska university hospital and Uppsala university hospital. Clinical data were reviewed until 2017., Results: We identified a total of 62 MS patients with at least one seizure. Median age at the first seizure (before or after MS) was 41 years (range 0-80). The most common MS disease course at the first seizure was secondary progressive MS, the neurological disability was considerable, and most patients had several MRI lesions at their first seizure. The first EEG demonstrated epileptiform discharges in 38% and unspecific pathology in 40%. Current seizure status could be determined for 37 patients. Out of these, 46% had been seizure free for more than one year at last follow-up. The majority of patients (65%) were on monotherapy at last follow-up. Carbamazepine was the most commonly used first AED, with a retention rate of 52%. No individual AED was associated with a particularly high rate of seizure freedom. The most common reason for discontinuation of the first AED was side-effects., Conclusion: Seizure freedom rates were low, perhaps indicating a need for higher ambitions in management. Side effects of AEDs may be a particular concern when treating epilepsy in patients with MS., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS., Methods: All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers., Results: The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17-3.76) in patients with MS and 1.4% (95% CI 1.30-1.52) in controls (risk ratio 2.5, 95% CI 2.19-2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64-3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88-2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89-6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90-7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95-7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01-1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09-1.26 per EDSS step, p < 0.0001)., Conclusions: Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy., (© 2017 American Academy of Neurology.)