5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article
      a , b , , a , a , a , c , d , c , e , f , f , g , h , i , j , i , j , k , k , l , l , m , m , n , o , p , EpiPGX Consortium ao , q , q , r , s , s , t , t , u , u , v , w , x , y , y , z , aa , ab , ac , ac , ad , ad , ae , af , ag , ag , ah , ai , aj , ak , al , ah , t , am , an , b , a , ap , a , ap
      eClinicalMedicine
      Elsevier
      Juvenile myoclonic epilepsy, Prediction model, Refractory epilepsy, Drug resistance, Medication withdrawal, Remission, Multivariable prediction, JME, Seizure recurrence, Meta-analysis, Individual participant data

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Summary

          Background

          A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

          Methods

          We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed – last updated on March 11, 2021 – including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/).

          Findings

          Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68–0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68–0·73).

          Interpretation

          We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools.

          Funding

          MING fonds.

          Related collections

          Most cited references61

          • Record: found
          • Abstract: not found
          • Article: not found

          Measuring inconsistency in meta-analyses.

            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            An introduction to ROC analysis

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Receiver operating characteristic curve in diagnostic test assessment.

              The performance of a diagnostic test in the case of a binary predictor can be evaluated using the measures of sensitivity and specificity. However, in many instances, we encounter predictors that are measured on a continuous or ordinal scale. In such cases, it is desirable to assess performance of a diagnostic test over the range of possible cutpoints for the predictor variable. This is achieved by a receiver operating characteristic (ROC) curve that includes all the possible decision thresholds from a diagnostic test result. In this brief report, we discuss the salient features of the ROC curve, as well as discuss and interpret the area under the ROC curve, and its utility in comparing two different tests or predictor variables of interest.
                Bookmark

                Author and article information

                Contributors
                Journal
                eClinicalMedicine
                EClinicalMedicine
                eClinicalMedicine
                Elsevier
                2589-5370
                11 November 2022
                November 2022
                11 November 2022
                : 53
                : 101732
                Affiliations
                [a ]Department of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands
                [b ]Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands
                [c ]Epilepsy Research Center, Shiraz University of Medical Sciences, Zand, Shiraz, Iran
                [d ]Department of Neurology, Thomas Jefferson University, 909 Walnut Street, Philadelphia, PA, 19107, USA
                [e ]Department of Neurology, Unidade Local de Saude do Alto Minho, Estrada de Santa Luzia, Viana do Castelo, 4904-858, Portugal
                [f ]Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 500003, India
                [g ]Department of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpaşa, Kocamustafapaşa caddesi, Istanbul, 34098, Turkey
                [h ]Department of Neurology, Yedikule Chest Diseases and Chest Surgery Training and Research Hospital, University of Health Sciences, Belgrat Kapı yolu, Istanbul, 34020, Turkey
                [i ]Department of Neurology, Odense University Hospital, J.B. Winsløws Vej 4, Odense, 5000, Denmark
                [j ]Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 4, Odense, 5000, Denmark
                [k ]Epilepsy Unit, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK
                [l ]Department of Neurology, R. Madhavan Nayar Center for Comprehensive Epilepsy Care, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Chalakkuzhi, Medical College Road, Trivandrum, 695011, India
                [m ]Department of Neurology and Neuroscience Institute, Christian Doppler Medical Centre, Paracelsus Medical University and Centre for Cognitive Neuroscience, European Reference Network EpiCARE, Ignaz-Harrer Straße 79, Salzburg, 5020, Austria
                [n ]Karl Landsteiner Institute for Neurorehabilitation and Space Neurology, Hellbrunner Straße 34, Salzburg, 3100, Austria
                [o ]Department of Public Health, University for Health Sciences, Medical Informatics and Technology, Eduard-Wallnöfer-Zentrum 1, Hall in Tirol, 6060, Austria
                [p ]Bioinformatics Core Facility, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 Ave du Swing, Belvaux, 4367, Luxembourg
                [q ]Department of Human Neurosciences, Epilepsy Unit, Sapienza, University of Rome, Viale dell'Università 30, Rome, 00185, Italy
                [r ]Departments of Neurology, Neurosurgery, and Neurobiology, UAB Epilepsy Center, University of Alabama at Birmingham Heersink School of Medicine, 1670 University Blvd, Birmingham, AL, 35294, USA
                [s ]Department of Clinical Research, Epilepsy Clinic, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877, Mexico, 14269, Mexico
                [t ]Department of Neurology, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610000, China
                [u ]Department of Neuroscience, Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, 00165, Italy
                [v ]Department of Clinical Neurophysiology, Institute of Neurology and Neuropsychology, 83/11 Vazha-Pshavela Ave., Tbilisi, 186, Georgia
                [w ]Department of Clinical Neurophysiology, Danish Epilepsy Centre, Filadelfia, Visby Allé 5, Dianalund, 4293, Denmark
                [x ]Department of Clinical Neurophysiology, Aarhus University Hospital and Aarhus University, Palle Juul-Jensens Blvd. 99, Aarhus, 8200, Denmark
                [y ]Department of Neurosciences, Central Clinical School, Monash University, 99 Commercial Road, Melbourne, Victoria, 3004, Australia
                [z ]Departments of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Grattan Street, Parkville, Victoria, Australia
                [aa ]Department of Neurology, Vestre Viken Hospital Trust, Dronninggata 28, Drammen, 3004, Norway
                [ab ]National Centre for Epilepsy & Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, G. F. Henriksens vei 29, Sandvika, 1337, Norway
                [ac ]Department of Neurology, Epilepsy-Center Berlin-Brandenburg, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany
                [ad ]Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India
                [ae ]Department of Neurology and Clinical Neurophysiology, Istanbul Faculty of Medicine, Istanbul University, Millet Cad, Istanbul, 34390, Turkey
                [af ]Department of Neurology, Istanbul Florence Nightingale Hospital, Abide-i Hürriyet Cad, Istanbul, 34381, Turkey
                [ag ]Department of Neurology, Epilepsy Center, University Medicine Greifswald, Sauerbruchstraße, Greifswald, 17489, Germany
                [ah ]Department of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, 55 Victoria Parade, Melbourne, Victoria, 3065, Australia
                [ai ]Department of Medicine, The School of Clinical Sciences at Monash Health, Monash University, Clayton Road, Melbourne, Victoria, 3168, Australia
                [aj ]Department of Neurology, Hospital General de la Defensa, Vía Ibérica 1, Zaragoza, 50009, Spain
                [ak ]Instituto de Investigación Sanitaria (IIS) Aragón, Avda. San Juan Bosco 13, Zaragoza, 50009, Spain
                [al ]Department of Neurology, Emory University School of Medicine, 49 Jesse Hill Jr. Drive SE, Office 335, Atlanta, GA, 30303, USA
                [am ]Stichting Epilepsie Instellingen Nederland (SEIN), Achterweg 7, Heemstede, Netherlands
                [an ]UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK
                Author notes
                []Corresponding author. Department of Child Neurology, University Medical Center Utrecht, 3584 CX, Utrecht, Netherlands. R.Stevelink-4@ 123456umcutrecht.nl
                [ao]

                EpiPGX Consortium members are listed in the supplementary materials.

                [ap]

                These authors contributed equally.

                Article
                S2589-5370(22)00462-X 101732
                10.1016/j.eclinm.2022.101732
                9716332
                36467455
                d516ea8a-0236-49af-8938-a348eda028d4
                © 2022 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 August 2022
                : 14 October 2022
                : 18 October 2022
                Categories
                Articles

                juvenile myoclonic epilepsy,prediction model,refractory epilepsy,drug resistance,medication withdrawal,remission,multivariable prediction,jme,seizure recurrence,meta-analysis,individual participant data

                Comments

                Comment on this article