{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T17:25:07Z","timestamp":1793899507374,"version":"4.8.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol. Res. Pract."],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Depending on the underlying etiology and epilepsy type, the burden of disease for patients with seizures can vary significantly. This analysis aimed to compare direct and indirect costs and quality of life (QoL) among adults with tuberous sclerosis complex (TSC) related with epilepsy, idiopathic generalized epilepsy (IGE), and focal epilepsy (FE) in Germany.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Questionnaire responses from 92 patients with TSC and epilepsy were matched by age and gender, with responses from 92 patients with IGE and 92 patients with FE collected in independent studies. Comparisons were made across the main QoL components, direct costs (patient visits, medication usage, medical equipment, diagnostic procedures, ancillary treatments, and transport costs), indirect costs (employment, reduced working hours, missed days), and care level costs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Across all three cohorts, mean total direct costs (TSC: \u20ac7602 [median \u20ac2620]; IGE: \u20ac1919 [median \u20ac446], <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; FE: \u20ac2598 [median \u20ac892], <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and mean total indirect costs due to lost productivity over 3 months (TSC: \u20ac7185 [median \u20ac11,925]; IGE: \u20ac3599 [median \u20ac0], <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; FE: \u20ac5082 [median \u20ac2981], <jats:italic>P<\/jats:italic>\u2009=\u20090.03) were highest among patients with TSC. The proportion of patients with TSC who were unemployed (60%) was significantly larger than the proportions of patients with IGE (23%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) or FE (34%, <jats:italic>P<\/jats:italic>\u2009=\u2009<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) who were unemployed. Index scores for the EuroQuol Scale with 5 dimensions and 3 levels were significantly lower for patients with TSC (time-trade-off [TTO]: 0.705, visual analog scale [VAS]: 0.577) than for patients with IGE (TTO: 0.897, VAS: 0.813; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) or FE (TTO: 0.879, VAS: 0.769; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Revised Epilepsy Stigma Scale scores were also significantly higher for patients with TSC (3.97) than for patients with IGE (1.48, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) or FE (2.45, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Overall Quality of Life in Epilepsy Inventory-31 items scores was significantly lower among patients with TSC (57.7) and FE (57.6) than among patients with IGE (66.6, <jats:italic>P<\/jats:italic>\u2009=\u20090.004 in both comparisons). Significant differences between patients with TSC and IGE were also determined for Neurological Disorder Depression Inventory for Epilepsy (TSC: 13.1; IGE: 11.2, <jats:italic>P<\/jats:italic>\u2009=\u20090.009) and Liverpool Adverse Events Profile scores (TSC: 42.7; IGE: 37.5, <jats:italic>P<\/jats:italic>\u2009=\u20090.017) with higher score and worse results for TSC patients in both questionnaires.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study is the first to compare patients with TSC, IGE, and FE in Germany and underlines the excessive QoL burden and both direct and indirect cost burdens experienced by patients with TSC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s42466-024-00323-6","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:01:41Z","timestamp":1717027301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A multicenter, matched case\u2013control analysis comparing burden of illness among patients with tuberous sclerosis complex related epilepsy, generalized idiopathic epilepsy, and focal epilepsy in Germany"],"prefix":"10.1186","volume":"6","author":[{"given":"Lisa","family":"Lappe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hertzberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Knake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Knuf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"von Podewils","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent M.","family":"Willems","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stjepana","family":"Kovac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann Philipp","family":"Z\u00f6llner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kurlemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Bertsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Marquard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Thiels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Zukunft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Schubert-Bast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Peter","family":"Reese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Rosenow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6288-9915","authenticated-orcid":false,"given":"Adam","family":"Strzelczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"issue":"1","key":"323_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13023-018-0870-y","volume":"13","author":"D Ebrahimi-Fakhari","year":"2018","unstructured":"Ebrahimi-Fakhari, D., Mann, L. L., Poryo, M., Graf, N., von Kries, R., Heinrich, B., et al. (2018). Incidence of tuberous sclerosis and age at first diagnosis: New data and emerging trends from a national, prospective surveillance study. Orphanet Journal of Rare Diseases, 13(1), 117. https:\/\/doi.org\/10.1186\/s13023-018-0870-y","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"1","key":"323_CR2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/epi4.12286","volume":"4","author":"R Nabbout","year":"2019","unstructured":"Nabbout, R., Belousova, E., Benedik, M. P., Carter, T., Cottin, V., Curatolo, P., et al. (2019). Epilepsy in tuberous sclerosis complex: Findings from the TOSCA study. Epilepsia Open, 4(1), 73\u201384. https:\/\/doi.org\/10.1002\/epi4.12286","journal-title":"Epilepsia Open"},{"key":"323_CR3","doi-asserted-by":"publisher","unstructured":"Rosset, C., Netto, C. B. O., & Ashton-Prolla, P. (2017). TSC1 and TSC2 gene mutations and their implications for treatment in tuberous sclerosis complex: A review. Genetics and Molecular Biology, 40(1), 69\u201379. https:\/\/doi.org\/10.1590\/1678-4685-GMB-2015-0321","DOI":"10.1590\/1678-4685-GMB-2015-0321"},{"key":"323_CR4","doi-asserted-by":"publisher","unstructured":"Dorn, T. (2022). Tuberous sclerosis complex (TSC). Zeitschrift f\u00fcr Epileptologie, 35(3), 242\u2013249. https:\/\/doi.org\/10.1007\/s10309-022-00512-w","DOI":"10.1007\/s10309-022-00512-w"},{"issue":"7","key":"323_CR5","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1111\/j.1528-1167.2009.02474.x","volume":"51","author":"CJ Chu-Shore","year":"2010","unstructured":"Chu-Shore, C. J., Major, P., Camposano, S., Muzykewicz, D., & Thiele, E. A. (2010). The natural history of epilepsy in tuberous sclerosis complex. Epilepsia, 51(7), 1236\u20131241. https:\/\/doi.org\/10.1111\/j.1528-1167.2009.02474.x","journal-title":"Epilepsia"},{"issue":"7","key":"323_CR6","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/S1474-4422(15)00069-1","volume":"14","author":"P Curatolo","year":"2015","unstructured":"Curatolo, P., Moavero, R., & de Vries, P. J. (2015). Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurology, 14(7), 733\u2013745. https:\/\/doi.org\/10.1016\/S1474-4422(15)00069-1","journal-title":"Lancet Neurology"},{"issue":"1","key":"323_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s13023-019-1258-3","volume":"15","author":"JP Zollner","year":"2020","unstructured":"Z\u00f6llner, J. P., Franz, D. N., Hertzberg, C., Nabbout, R., Rosenow, F., Sauter, M., et al. (2020). A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC). Orphanet Journal of Rare Diseases, 15(1), 23. https:\/\/doi.org\/10.1186\/s13023-019-1258-3","journal-title":"Orphanet Journal of rare Diseases"},{"key":"323_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.ejpn.2023.08.005","volume":"47","author":"N Specchio","year":"2023","unstructured":"Specchio, N., Nabbout, R., Aronica, E., Auvin, S., Benvenuto, A., de Palma, L., et al. (2023). Updated clinical recommendations for the management of tuberous sclerosis complex associated epilepsy. European Journal of Paediatric Neurology,47, 25\u201334. https:\/\/doi.org\/10.1016\/j.ejpn.2023.08.005","journal-title":"European Journal of Paediatric Neurology: EJPN : Official Journal of the European Paediatric Neurology Society"},{"key":"323_CR9","doi-asserted-by":"publisher","unstructured":"Strzelczyk, A., Kurlemann, G., Bast, T., Bettendorf, U., Kluger, G., Mayer, T., et al. (2022). Exploring the relationships between composite scores of disease severity seizure-freedom and quality of life in Dravet syndrome. Neurological Research and Practice, 4(1), 22. https:\/\/doi.org\/10.1186\/s42466-022-00186-9","DOI":"10.1186\/s42466-022-00186-9"},{"issue":"6","key":"323_CR10","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1111\/epi.17229","volume":"63","author":"LM Willems","year":"2022","unstructured":"Willems, L. M., Hochbaum, M., Z\u00f6llner, J. P., Schulz, J., Menzler, K., Langenbruch, L., et al. (2022). Trends in resource utilization and cost of illness in patients with active epilepsy in Germany from 2003 to 2020. Epilepsia, 63(6), 1591\u20131602. https:\/\/doi.org\/10.1111\/epi.17229","journal-title":"Epilepsia"},{"issue":"4","key":"323_CR11","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1111\/epi.17174","volume":"63","author":"LM Willems","year":"2022","unstructured":"Willems, L. M., Hochbaum, M., Frey, K., Schulz, J., Menzler, K., Langenbruch, L., et al. (2022). Multicenter, cross-sectional study of the costs of illness and cost-driving factors in adult patients with epilepsy. Epilepsia, 63(4), 904\u2013918. https:\/\/doi.org\/10.1111\/epi.17174","journal-title":"Epilepsia"},{"issue":"6","key":"323_CR12","doi-asserted-by":"publisher","first-page":"463","DOI":"10.2165\/00019053-200826060-00002","volume":"26","author":"A Strzelczyk","year":"2008","unstructured":"Strzelczyk, A., Reese, J. P., Dodel, R., & Hamer, H. M. (2008). Cost of epilepsy: A systematic review. Pharmacoeconomics, 26(6), 463\u2013476.","journal-title":"Pharmacoeconomics"},{"issue":"11","key":"323_CR13","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1080\/13696998.2016.1199432","volume":"19","author":"JC Kingswood","year":"2016","unstructured":"Kingswood, J. C., Crawford, P., Johnson, S. R., Sampson, J. R., Shepherd, C., Demuth, D., et al. (2016). The economic burden of tuberous sclerosis complex in the UK: A retrospective cohort study in the clinical practice research datalink. Journal of Medical Economics, 19(11), 1087\u20131098. https:\/\/doi.org\/10.1080\/13696998.2016.1199432","journal-title":"Journal of Medical Economics"},{"issue":"12","key":"323_CR14","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1080\/13696998.2016.1202254","volume":"19","author":"JC Kingswood","year":"2016","unstructured":"Kingswood, J. C., Nasuti, P., Patel, K., Myland, M., Siva, V., & Gray, E. (2016). The economic burden of tuberous sclerosis complex in UK patients with renal manifestations: A retrospective cohort study in the clinical practice research datalink (CPRD). Journal of Medical Economics, 19(12), 1116\u20131126. https:\/\/doi.org\/10.1080\/13696998.2016.1202254","journal-title":"Journal of Medical Economics"},{"issue":"1","key":"323_CR15","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1186\/s13023-021-01899-x","volume":"16","author":"J Grau","year":"2021","unstructured":"Grau, J., Z\u00f6llner, J. P., Schubert-Bast, S., Kurlemann, G., Hertzberg, C., Wiemer-Kruel, A., et al. (2021). Direct and indirect costs and cost-driving factors of tuberous sclerosis complex in children, adolescents, and caregivers: A multicenter cohort study. Orphanet Journal of Rare Diseases, 16(1), 282. https:\/\/doi.org\/10.1186\/s13023-021-01899-x","journal-title":"Orphanet Journal of rare Diseases"},{"issue":"1","key":"323_CR16","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s42466-021-00130-3","volume":"3","author":"JP Zollner","year":"2021","unstructured":"Z\u00f6llner, J. P., Conradi, N., Sauter, M., Knuf, M., Knake, S., Kurlemann, G., et al. (2021). Quality of life and its predictors in adults with tuberous sclerosis complex (TSC): A multicentre cohort study from Germany. Neurological Research and Practice, 3(1), 35. https:\/\/doi.org\/10.1186\/s42466-021-00130-3","journal-title":"Neurol Res Pract"},{"issue":"1","key":"323_CR17","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/s13023-021-01838-w","volume":"16","author":"JP Zollner","year":"2021","unstructured":"Z\u00f6llner, J. P., Grau, J., Rosenow, F., Sauter, M., Knuf, M., Kurlemann, G., et al. (2021). Direct and indirect costs and cost-driving factors in adults with tuberous sclerosis complex: A multicenter cohort study and a review of the literature. Orphanet Journal of Rare Diseases, 16(1), 250. https:\/\/doi.org\/10.1186\/s13023-021-01838-w","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"1","key":"323_CR18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s42466-022-00209-5","volume":"4","author":"K Korbel","year":"2022","unstructured":"K\u00f6rbel, K., Rosenow, F., Maltseva, M., Muller, H., Schulz, J., Tsalouchidou, P. E., et al. (2022). Impact of COVID-19 pandemic on physical and mental health status and care of adults with epilepsy in Germany. Neurological Research and Practice, 4(1), 44. https:\/\/doi.org\/10.1186\/s42466-022-00209-5","journal-title":"Neurol Res Pract"},{"key":"323_CR19","doi-asserted-by":"publisher","first-page":"108666","DOI":"10.1016\/j.yebeh.2022.108666","volume":"130","author":"M Hochbaum","year":"2022","unstructured":"Hochbaum, M., Kienitz, R., Rosenow, F., Schulz, J., Habermehl, L., Langenbruch, L., et al. (2022). Trends in antiseizure medication prescription patterns among all adults, women, and older adults with epilepsy: A German longitudinal analysis from 2008 to 2020. Epilepsy & Behavior, 130, 108666. https:\/\/doi.org\/10.1016\/j.yebeh.2022.108666","journal-title":"Epilepsy & Behavior"},{"issue":"1","key":"323_CR20","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s42466-023-00265-5","volume":"5","author":"K Siebenbrodt","year":"2023","unstructured":"Siebenbrodt, K., Willems, L. M., von Podewils, F., Mross, P. M., Struber, M., Langenbruch, L., et al. (2023). Determinants of quality of life in adults with epilepsy: A multicenter, cross-sectional study from Germany. Neurol Res Pract, 5(1), 41. https:\/\/doi.org\/10.1186\/s42466-023-00265-5","journal-title":"Neurol Res Pract"},{"key":"323_CR21","doi-asserted-by":"publisher","first-page":"109255","DOI":"10.1016\/j.yebeh.2023.109255","volume":"144","author":"LM Willems","year":"2023","unstructured":"Willems, L. M., Z\u00f6llner, J. P., Hamann, L., Knake, S., Kovac, S., von Podewils, F., et al. (2023). Unemployment and early retirement among patients with epilepsy - A study on predictors, resilience factors and occupational reintegration measures. Epilepsy & Behavior, 144, 109255. https:\/\/doi.org\/10.1016\/j.yebeh.2023.109255","journal-title":"Epilepsy & Behavior"},{"issue":"6","key":"323_CR22","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s40263-023-01013-8","volume":"37","author":"LM Willems","year":"2023","unstructured":"Willems, L. M., van der Goten, M., von Podewils, F., Knake, S., Kovac, S., Z\u00f6llner, J. P., et al. (2023). Adverse event profiles of antiseizure medications and the impact of coadministration on drug tolerability in adults with epilepsy. CNS Drugs, 37(6), 531\u2013544. https:\/\/doi.org\/10.1007\/s40263-023-01013-8","journal-title":"CNS Drugs"},{"issue":"4","key":"323_CR23","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1111\/epi.13709","volume":"58","author":"IE Scheffer","year":"2017","unstructured":"Scheffer, I. E., Berkovic, S., Capovilla, G., Connolly, M. B., French, J., Guilhoto, L., et al. (2017). ILAE classification of the epilepsies: Position paper of the ILAE commission for classification and terminology. Epilepsia, 58(4), 512\u2013521. https:\/\/doi.org\/10.1111\/epi.13709","journal-title":"Epilepsia"},{"issue":"4","key":"323_CR24","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/epi.13670","volume":"58","author":"RS Fisher","year":"2017","unstructured":"Fisher, R. S., Cross, J. H., French, J. A., Higurashi, N., Hirsch, E., Jansen, F. E., et al. (2017). Operational classification of seizure types by the international league against epilepsy: Position paper of the ILAE commission for classification and terminology. Epilepsia, 58(4), 522\u2013530. https:\/\/doi.org\/10.1111\/epi.13670","journal-title":"Epilepsia"},{"issue":"4","key":"323_CR25","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","volume":"49","author":"H Northrup","year":"2013","unstructured":"Northrup, H., & Krueger (2013). D. A (Ed.), International tuberous sclerosis complex consensus G tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatric Neurology 49 4 243\u2013254 https:\/\/doi.org\/10.1016\/j.pediatrneurol.2013.08.001","journal-title":"Pediatric Neurology"},{"issue":"9596","key":"323_CR26","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","volume":"370","author":"E von Elm","year":"2007","unstructured":"von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gotzsche, P. C., Vandenbroucke, J. P., et al. (2007). The strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. Lancet, 370(9596), 1453\u20131457. https:\/\/doi.org\/10.1016\/S0140-6736(07)61602-X","journal-title":"Lancet"},{"key":"323_CR27","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1374621","author":"JO Bock","year":"2015","unstructured":"Bock, J. O., Brettschneider, C., Seidl, H., Bowles, D., Holle, R., Greiner, W. (2015). Calculation of standardised unit costs from a societal perspective for health economic evaluation. Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany)). 77(1):53\u201361. https:\/\/doi.org\/10.1055\/s-0034-1374621"},{"issue":"11","key":"323_CR28","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1055\/a-0795-3319","volume":"81","author":"M Schwendler","year":"2019","unstructured":"Schwendler, M., & Flessa, S. (2019). The calculated physician\u2019s fee in the Doctor\u2019s fee scale (EBM): A normative parameter for medical doctors in the outpatient sector. Gesundheitswesen, 81(11), 919\u2013925. https:\/\/doi.org\/10.1055\/a-0795-3319","journal-title":"Gesundheitswesen (Bundesverband Der Arzte Des Offentlichen Gesundheitsdienstes (Germany))"},{"key":"323_CR29","doi-asserted-by":"crossref","unstructured":"Schwabe, U., & Ludwig, W. D. (2020). Arzneiverordnungs-Report 2020. Springer Nature.","DOI":"10.1007\/978-3-662-62168-4"},{"issue":"3","key":"323_CR30","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1002\/epi4.12737","volume":"8","author":"H Hersi","year":"2023","unstructured":"Hersi, H., Raitanen, J., Saarinen, J. T., & Peltola, J. (2023). Prescribed antiseizure medication doses and their relation to defined daily doses for achieving seizure freedom in newly diagnosed patients with epilepsy. Epilepsia Open, 8(3), 811\u2013819. https:\/\/doi.org\/10.1002\/epi4.12737","journal-title":"Epilepsia Open"},{"issue":"3","key":"323_CR31","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","volume":"16","author":"EuroQol Group","year":"1990","unstructured":"EuroQol Group. (1990). EuroQol - a new facility for the measurement of health-related quality of life. Health Policy, 16(3), 199\u2013208.","journal-title":"Health Policy (Amsterdam Netherlands)"},{"issue":"1","key":"323_CR32","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1528-1157.1998.tb01278.x","volume":"39","author":"JA Cramer","year":"1998","unstructured":"Cramer, J. A., Perrine, K., Devinsky, O., Bryant-Comstock, L., Meador, K., & Hermann, B. (1998). Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory. Epilepsia, 39(1), 81\u201388. https:\/\/doi.org\/10.1111\/j.1528-1157.1998.tb01278.x","journal-title":"Epilepsia"},{"issue":"5","key":"323_CR33","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/S1474-4422(06)70415-X","volume":"5","author":"FG Gilliam","year":"2006","unstructured":"Gilliam, F. G., Barry, J. J., Hermann, B. P., Meador, K. J., Vahle, V., & Kanner, A. M. (2006). Rapid detection of major depression in epilepsy: A multicentre study. Lancet Neurology, 5(5), 399\u2013405. https:\/\/doi.org\/10.1016\/S1474-4422(06)70415-X","journal-title":"Lancet Neurology"},{"key":"323_CR34","doi-asserted-by":"publisher","first-page":"109179","DOI":"10.1016\/j.yebeh.2023.109179","volume":"142","author":"A Strzelczyk","year":"2023","unstructured":"Strzelczyk, A., Aledo-Serrano, A., Coppola, A., Didelot, A., Bates, E., Sainz-Fuertes, R., et al. (2023). The impact of epilepsy on quality of life: Findings from a European survey. Epilepsy & Behavior, 142, 109179. https:\/\/doi.org\/10.1016\/j.yebeh.2023.109179","journal-title":"Epilepsy &amp; Behavior: E&amp;B"},{"key":"323_CR35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.yebeh.2018.01.028","volume":"81","author":"M Romoli","year":"2018","unstructured":"Romoli, M., Eusebi, P., Siliquini, S., Bedetti, C., Calabresi, P., & Costa, C. (2018). Liverpool adverse events profile: Italian validation and predictive value for dropout from antiepileptic treatment in people with epilepsy. Epilepsy & Behavior, 81, 111\u2013114. https:\/\/doi.org\/10.1016\/j.yebeh.2018.01.028","journal-title":"Epilepsy & Behavior"},{"issue":"1","key":"323_CR36","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/j.1528-1157.2000.tb01512.x","volume":"41","author":"GA Baker","year":"2000","unstructured":"Baker, G. A., Brooks, J., Buck, D., & Jacoby, A. (2000). The stigma of epilepsy: A European perspective. Epilepsia, 41(1), 98\u2013104. https:\/\/doi.org\/10.1111\/j.1528-1157.2000.tb01512.x","journal-title":"Epilepsia"},{"issue":"2","key":"323_CR37","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.seizure.2013.10.008","volume":"23","author":"I Bielen","year":"2014","unstructured":"Bielen, I., Friedrich, L., Sruk, A., Prvan, M. P., Hajnsek, S., Petelin, Z., et al. (2014). Factors associated with perceived stigma of epilepsy in Croatia: A study using the revised epilepsy stigma scale. Seizure, 23(2), 117\u2013121. https:\/\/doi.org\/10.1016\/j.seizure.2013.10.008","journal-title":"Seizure"},{"issue":"5","key":"323_CR38","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1111\/j.1528-1167.2010.02973.x","volume":"52","author":"A Jacoby","year":"2011","unstructured":"Jacoby, A., Lane, S., Marson, A., & Baker, G. A. (2011). Relationship of clinical and quality of life trajectories following the onset of seizures: Findings from the UK MESS Study. Epilepsia, 52(5), 965\u2013974.","journal-title":"Epilepsia"},{"issue":"5 Pt 1","key":"323_CR39","doi-asserted-by":"publisher","first-page":"487","DOI":"10.2165\/00019053-199813050-00002","volume":"13","author":"A Desgagne","year":"1998","unstructured":"Desgagne, A., Castilloux, A. M., Angers, J. F., & LeLorier, J. (1998). The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data. Pharmacoeconomics, 13(5 Pt 1), 487\u2013497.","journal-title":"Pharmacoeconomics"},{"issue":"23","key":"323_CR40","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1002\/1097-0258(20001215)19:23<3219::AID-SIM623>3.0.CO;2-P","volume":"19","author":"JA Barber","year":"2000","unstructured":"Barber, J. A., & Thompson, S. G. (2000). Analysis of cost data in randomized trials: An application of the non-parametric bootstrap. Statistics in Medicine, 19(23), 3219\u20133236.","journal-title":"Statistics in Medicine"},{"key":"323_CR41","doi-asserted-by":"publisher","first-page":"904","DOI":"10.3389\/fneur.2020.00904","volume":"11","author":"AC Jansen","year":"2020","unstructured":"Jansen, A. C., Vanclooster, S., de Vries, P. J., Fladrowski, C., Beaure d\u2019Augeres, G., Carter, T., et al. (2020). Burden of illness and quality of life in tuberous sclerosis complex: Findings from the TOSCA study. Frontiers in Neurology, 11, 904. https:\/\/doi.org\/10.3389\/fneur.2020.00904","journal-title":"Frontiers in Neurology"},{"issue":"4","key":"323_CR42","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1002\/epi4.12636","volume":"7","author":"F Fagnani","year":"2022","unstructured":"Fagnani, F., Laurendeau, C., de Zelicourt, M., & Marshall, J. (2022). Epidemiology and disease burden of tuberous sclerosis complex in France: A population-based study based on national health insurance data. Epilepsia Open, 7(4), 633\u2013644. https:\/\/doi.org\/10.1002\/epi4.12636","journal-title":"Epilepsia Open"},{"issue":"1","key":"323_CR43","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13023-020-01517-2","volume":"15","author":"WC Chu","year":"2020","unstructured":"Chu, W. C., Chiang, L. L., Chan, D. C., Wong, W. H., & Chan, G. C. (2020). Prevalence, mortality and healthcare economic burden of tuberous sclerosis in Hong Kong: A population-based retrospective cohort study (1995\u20132018). Orphanet Journal of Rare Diseases, 15(1), 264. https:\/\/doi.org\/10.1186\/s13023-020-01517-2","journal-title":"Orphanet Journal of rare Diseases"},{"issue":"2","key":"323_CR44","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s41669-023-00387-1","volume":"7","author":"H Skrobanski","year":"2023","unstructured":"Skrobanski, H., Vyas, K., Bowditch, S., Hubig, L., Dziadulewicz, E., Fish, L., et al. (2023). The burden of caring for individuals with tuberous sclerosis complex (TSC) who experience epileptic seizures: A descriptive UK survey. Pharmacoecon Open, 7(2), 299\u2013312. https:\/\/doi.org\/10.1007\/s41669-023-00387-1","journal-title":"Pharmacoecon Open"},{"key":"323_CR45","doi-asserted-by":"publisher","unstructured":"Kerling, F. (2022). New developments in anticonvulsive therapy for people with intellectual disability. Zeitschrift f\u00fcr Epileptologie, 35(3), 225\u2013229. https:\/\/doi.org\/10.1007\/s10309-022-00509-5","DOI":"10.1007\/s10309-022-00509-5"},{"key":"323_CR46","doi-asserted-by":"publisher","first-page":"107494","DOI":"10.1016\/j.yebeh.2020.107494","volume":"112","author":"KA Betts","year":"2020","unstructured":"Betts, K. A., Stockl, K. M., Yin, L., Hollenack, K., Wang, M. J., & Yang, X. (2020). Economic burden associated with tuberous sclerosis complex in patients with epilepsy. Epilepsy & Behavior, 112, 107494. https:\/\/doi.org\/10.1016\/j.yebeh.2020.107494","journal-title":"Epilepsy & Behavior"},{"issue":"10","key":"323_CR47","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1007\/s40263-021-00839-4","volume":"35","author":"LM Willems","year":"2021","unstructured":"Willems, L. M., Rosenow, F., Schubert-Bast, S., Kurlemann, G., Z\u00f6llner, J. P., Bast, T., et al. (2021). Efficacy, retention and tolerability of everolimus in patients with tuberous sclerosis complex: A survey-based study on patients\u2019 perspectives. CNS Drugs, 35(10), 1107\u20131122. https:\/\/doi.org\/10.1007\/s40263-021-00839-4","journal-title":"Cns Drugs"},{"key":"323_CR48","doi-asserted-by":"publisher","unstructured":"Willems, L. M., Strzelczyk, A., & Rosenow, F. (2021). Everolimus as disease-specific treatment option in tuberous sclerosis complex-associated drug refractory epilepsy - a systematic review. Zeitschrift f\u00fcr Epileptologie, 34, 168\u2013174. https:\/\/doi.org\/10.1007\/s10309-020-00393-x","DOI":"10.1007\/s10309-020-00393-x"},{"issue":"10","key":"323_CR49","doi-asserted-by":"publisher","first-page":"e015236","DOI":"10.1136\/bmjopen-2016-015236","volume":"7","author":"C Shepherd","year":"2017","unstructured":"Shepherd, C., Koepp, M., Myland, M., Patel, K., Miglio, C., Siva, V., et al. (2017). Understanding the health economic burden of patients with tuberous sclerosis complex (TSC) with epilepsy: A retrospective cohort study in the UK clinical practice research datalink (CPRD). BMJ open, 7(10), e015236. https:\/\/doi.org\/10.1136\/bmjopen-2016-015236","journal-title":"BMJ open"},{"issue":"1","key":"323_CR50","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1186\/s13023-022-02385-8","volume":"17","author":"FVM Mulder","year":"2022","unstructured":"Mulder, F. V. M., Peeters, E., Westerink, J., Zwartkruis, F. J. T., & de Ranitz-Greven, W. L. (2022). The long-term effect of mTOR inhibition on lipid and glucose metabolism in tuberous sclerosis complex: Data from the Dutch TSC registry. Orphanet Journal of Rare Diseases, 17(1), 252. https:\/\/doi.org\/10.1186\/s13023-022-02385-8","journal-title":"Orphanet Journal of rare Diseases"},{"key":"323_CR51","unstructured":"Bundeszentrale f\u00fcr politische Bildung. Erwerbst\u00e4tigenquote nach Geschlecht und Alter. Available from https:\/\/www.bpb.de\/kurz-knapp\/zahlen-und-fakten\/soziale-situation-in-deutschland\/61688\/erwerbstaetigenquoten-nach-geschlecht-und-alter\/ [accessed 2023]."},{"issue":"10","key":"323_CR52","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1080\/13696998.2018.1487447","volume":"21","author":"AM Skalicky","year":"2018","unstructured":"Skalicky, A. M., Rentz, A. M., Liu, Z., Said, Q., Nakagawa, J. A., Frost, M. D., et al. (2018). Economic burden, work, and school productivity in individuals with tuberous sclerosis and their families. Journal of Medical Economics, 21(10), 953\u2013959. https:\/\/doi.org\/10.1080\/13696998.2018.1487447","journal-title":"Journal of Medical Economics"},{"issue":"9","key":"323_CR53","doi-asserted-by":"publisher","first-page":"e2589","DOI":"10.1002\/brb3.2589","volume":"12","author":"P Ioannou","year":"2022","unstructured":"Ioannou, P., Foster, D. L., Sander, J. W., Dupont, S., Gil-Nagel, A., Drogon O\u2019Flaherty, E., et al. (2022). The burden of epilepsy and unmet need in people with focal seizures. Brain Behav, 12(9), e2589. https:\/\/doi.org\/10.1002\/brb3.2589","journal-title":"Brain Behav"},{"issue":"9","key":"323_CR54","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1007\/s10198-021-01326-9","volume":"22","author":"MF Janssen","year":"2021","unstructured":"Janssen, M. F., Pickard, A. S., & Shaw, J. W. (2021). General population normative data for the EQ-5D-3L in the five largest European economies. The European Journal of Health Economics, 22(9), 1467\u20131475. https:\/\/doi.org\/10.1007\/s10198-021-01326-9","journal-title":"The European Journal of Health Economics"},{"issue":"2","key":"323_CR55","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/ana.25956","volume":"89","author":"K Kotulska","year":"2021","unstructured":"Kotulska, K., Kwiatkowski, D. J., Curatolo, P., Weschke, B., Riney, K., Jansen, F., et al. (2021). Prevention of epilepsy in infants with tuberous sclerosis complex in the EPISTOP trial. Annals of Neurology, 89(2), 304\u2013314. https:\/\/doi.org\/10.1002\/ana.25956","journal-title":"Annals of Neurology"},{"issue":"1","key":"323_CR56","doi-asserted-by":"publisher","first-page":"7664","DOI":"10.1038\/s41467-023-42855-6","volume":"14","author":"F Huschner","year":"2023","unstructured":"Huschner, F., Glowacka-Walas, J., Mills, J. D., Klonowska, K., Lasseter, K., Asara, J. M., et al. (2023). Molecular EPISTOP, a comprehensive multi-omic analysis of blood from tuberous sclerosis complex infants age birth to two years. Nature Communications, 14(1), 7664. https:\/\/doi.org\/10.1038\/s41467-023-42855-6","journal-title":"Nature Communications"}],"container-title":["Neurological Research and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42466-024-00323-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s42466-024-00323-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s42466-024-00323-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:02:01Z","timestamp":1717027321000},"score":1,"resource":{"primary":{"URL":"https:\/\/neurolrespract.biomedcentral.com\/articles\/10.1186\/s42466-024-00323-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,30]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["323"],"URL":"https:\/\/doi.org\/10.1186\/s42466-024-00323-6","relation":{"references":[{"id-type":"uri","id":"","asserted-by":"subject"}]},"ISSN":["2524-3489"],"issn-type":[{"value":"2524-3489","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,30]]},"assertion":[{"value":"2 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"We confirm that we have read the Journal\u2019s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The underlying studies received ethics approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent for publication"}},{"value":"All participants provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"LL and none of the other authors report conflicts of interest related to this study.CH reports personal fees from Desitin Arzneimittel, Eisai, GW Pharmaceuticals companies, Novartis, Shire, and Zogenix.SKn received speaker\u00b4s honoraria from Angelini Pharma, Bial, Desitin Arzneimittel, Eisai, Epliog, GW Pharmaceuticals, Kanso, UCB Pharma, and Zogenix.MK does not have any COI. He receives no honoraria from pharmaceutical companies.FvP reports personal fees and grants from Bial, Desitin Arzneimittel, Eisai, GW Pharmaceutical companies, Arvelle Therapeutics, Zogenix, and UCB Pharma.LW does not have any COI. He receives no honoraria from pharmaceutical companies.SKo reports speakers honoraria from Eisai, UCB and Jazz Pharma, and research funding from Biogen.JPZ does not have any COI. He receives no honoraria from pharmaceutical companies.MS reports personal fees from Novartis and GW Pharmaceuticals companies.GKu reports honoraria for speaking engagements from Desitin Arzneimittel, Eisai, UCB Pharma, Takeda, Shire, Zogenix, Neuraxpharm, Stada, and GW Pharmaceuticals.TM does not have any COI. He receives no honoraria from pharmaceutical companies.AB reports grants from UCB Pharma and honoraria for speaking engagements from Biogen, Desitin Arzneimittel, Eisai GmbH, GW Pharmaceuticals, Neuraxpharm, Shire\/Takeda GmbH, UCB Pharma, and ViroPharma.KM does not have any COI. He receives no honoraria from pharmaceutical companies.SM reports grants from Novartis, UCB, Shire, Deutsche Forschungsgemeinschaft und Epilepsiestiftung Dr. Wolf.HS does not have any COI. She receives no honoraria from pharmaceutical companies.CT does not have any COI. She receives no honoraria from pharmaceutical companies.BZ does not have any COI. She receives no honoraria from pharmaceutical companies.SSB reports personal fees from Eisai, Desitin Pharma, GW Pharmaceuticals, Zogenix, UCB Pharma, and Marinus Pharma.JPR does not have any COI. He receives no honoraria from pharmaceutical companies.FR reports personal fees from Angelini Pharma, Eisai, Jazz Pharma, and UCB Pharma and grants from the Detlev-Wrobel-Fonds for Epilepsy Research, the Deutsche Forschungsgemeinschaft (DFG), the Federal Ministry of Education and Research (BMBF), the LOEWE Programme of the State of Hesse, and the European Union. FR reports that he is part of the editorial board of Neurological Research and Practice.AS reports personal fees and grants from Angelini Pharma, Biocodex, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, Marinus Pharma, Precisis, Takeda, UCB Pharma, and UNEEG Medical. AS reports that he is part of the editorial board of Neurological Research and Practice.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}