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      Clinical risk factors in SUDEP : A nationwide population-based case-control study

      research-article
      , MD, MSc , , BSc, , MD, PhD, , PhD, , MD, PhD
      Neurology
      Lippincott Williams & Wilkins

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          Abstract

          Objective

          We conducted a nationwide case-control study in Sweden to test the hypothesis that specific clinical characteristics are associated with increased risk of sudden unexpected death in epilepsy (SUDEP).

          Methods

          The study included 255 SUDEP cases (definite and probable) and 1,148 matched controls. Clinical information was obtained from medical records and the National Patient Register. The association between SUDEP and potential risk factors was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) and interaction assessed by attributable proportion due to interaction (AP).

          Results

          Experiencing generalized tonic-clonic seizures (GTCS) during the preceding year was associated with a 27-fold increased risk (OR 26.81, 95% CI 14.86–48.38), whereas no excess risk was seen in those with exclusively non-GTCS seizures (OR 1.15, 95% CI 0.54–48.38). The presence of nocturnal GTCS during the last year of observation was associated with a 15-fold risk (OR 15.31, 95% CI 9.57–24.47). Living alone was associated with a 5-fold increased risk of SUDEP (OR 5.01, 95% CI 2.93–8.57) and interaction analysis showed that the combination of not sharing a bedroom and having GTCS conferred an OR of 67.10 (95% CI 29.66–151.88), with AP estimated at 0.69 (CI 0.53–0.85). Among comorbid diseases, a previous diagnosis of substance abuse or alcohol dependence was associated with excess risk of SUDEP.

          Conclusions

          Individuals with GTCS who sleep alone have a dramatically increased SUDEP risk. Our results indicate that 69% of SUDEP cases in patients who have GTCS and live alone could be prevented if the patients were not unattended at night or were free from GTCS.

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          Most cited references20

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          ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

          The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
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            The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research

            Education, income, and occupation are factors known to affect health and disease. In this review we describe the Swedish Longitudinal Integrated Database for Health Insurance and Labour Market Studies (LISA, Longitudinell Integrationsdatabas för Sjukförsäkrings- och Arbetsmarknadsstudier). LISA covers the adult Swedish population aged ≥ 16 years registered on December 31 each year since 1990 (since 2010 individuals aged ≥ 15 years). The database was launched in response to rising levels of sick leave in the country. Participation in Swedish government-administered registers such as LISA is compulsory, and hence selection bias is minimized. The LISA database allows researchers to identify individuals who do not work because of injury, disease, or rehabilitation. It contains data on sick leave and disability pension based on calendar year. LISA also includes information on unemployment benefits, disposable income, social welfare payments, civil status, and migration. During 2000–2017, an average of 97,000 individuals immigrated to Sweden each year. This corresponds to about 1% of the Swedish population (10 million people in 2017). Data on occupation have a completeness of 95%. Income data consist primarily of income from employment, capital, and allowances, including parental allowance. In Sweden, work force participation is around 80% (2017: overall: 79.1%; men 80.3% and women 77.9%). Education data are available in > 98% of all individuals aged 25–64 years, with an estimated accuracy for highest attained level of education of 85%. Some information on civil status, income, education, and employment before 1990 can be obtained through the Population and Housing Census data (FoB, Folk- och bostadsräkningen).
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              Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention.

              Sudden unexpected death in epilepsy (SUDEP) can affect individuals of any age, but is most common in younger adults (aged 20-45 years). Generalised tonic-clonic seizures are the greatest risk factor for SUDEP; most often, SUDEP occurs after this type of seizure in bed during sleep hours and the person is found in a prone position. SUDEP excludes other forms of seizure-related sudden death that might be mechanistically related (eg, death after single febrile, unprovoked seizures, or status epilepticus). Typically, postictal apnoea and bradycardia progress to asystole and death. A crucial element of SUDEP is brainstem dysfunction, for which postictal generalised EEG suppression might be a biomarker. Dysfunction in serotonin and adenosine signalling systems, as well as genetic disorders affecting cardiac conduction and neuronal excitability, might also contribute. Because generalised tonic-clonic seizures precede most cases of SUDEP, patients must be better educated about prevention. The value of nocturnal monitoring to detect seizures and postictal stimulation is unproven but warrants further study.
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                Author and article information

                Journal
                Neurology
                Neurology
                neurology
                neur
                neurology
                NEUROLOGY
                Neurology
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0028-3878
                1526-632X
                28 January 2020
                28 January 2020
                : 94
                : 4
                : e419-e429
                Affiliations
                From the Department of Neurology (O.S. T.T.), Karolinska University Hospital; Department of Clinical Neuroscience (O.S. T.T.) and Institute of Environmental Medicine (T.A., S.C.), Karolinska Institutet; Center for Occupational and Environmental Medicine (T.A.), Stockholm County Council; and Department of Neuroscience (P.M.), University of Uppsala, Sweden.
                Author notes
                Correspondence Dr. Sveinsson olafur.sveinsson@ 123456sll.se

                Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

                The Article Processing Charge was funded by CURE foundation.

                Article
                NEUROLOGY2019995761 00012
                10.1212/WNL.0000000000008741
                7079690
                31831600
                69203380-5cf0-4bb8-b106-b6ebab9b57f8
                Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 04 May 2019
                : 05 August 2019
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