Evidence map›Paper›PMID 36467455›Full record

ArticleEClinicalMedicine2022

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.

Remi Stevelink, Dania Al-Toma, Floor E Jansen, Herm J Lamberink, Ali A Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara and 42 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors at 20 institutions in 17 countries.

Remi StevelinkDepartment of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
Dania Al-TomaDepartment of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
Floor E JansenDepartment of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
Herm J LamberinkDepartment of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
Ali A Asadi-PooyaEpilepsy Research Center, Shiraz University of Medical Sciences, Zand, Shiraz, Iran.
Mohsen FarazdaghiEpilepsy Research Center, Shiraz University of Medical Sciences, Zand, Shiraz, Iran.
Gonçalo CaçãoDepartment of Neurology, Unidade Local de Saude do Alto Minho, Estrada de Santa Luzia, Viana do Castelo, 4904-858, Portugal.
Sita JayalakshmiDepartment of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 500003, India.
Anuja PatilDepartment of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 500003, India.
Çiğdem ÖzkaraDepartment of Neurology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpaşa, Kocamustafapaşa caddesi, Istanbul, 34098, Turkey.
Şenay AydınDepartment of Neurology, Yedikule Chest Diseases and Chest Surgery Training and Research Hospital, University of Health Sciences, Belgrat Kapı yolu, Istanbul, 34020, Turkey.
Joanna GescheDepartment of Neurology, Odense University Hospital, J.B. Winsløws Vej 4, Odense, 5000, Denmark.
Christoph P BeierDepartment of Neurology, Odense University Hospital, J.B. Winsløws Vej 4, Odense, 5000, Denmark.
Linda J StephenEpilepsy Unit, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
Martin J BrodieEpilepsy Unit, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
Gopeekrishnan UnnithanDepartment 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.
Ashalatha RadhakrishnanDepartment 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.
Julia HöflerDepartment 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.
Eugen TrinkaDepartment 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.
Roland KrauseBioinformatics Core Facility, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 Ave du Swing, Belvaux, 4367, Luxembourg.
EpiPGX Consortium
Emanuele Cerulli IrelliDepartment of Human Neurosciences, Epilepsy Unit, Sapienza, University of Rome, Viale dell'Università 30, Rome, 00185, Italy.
Carlo Di BonaventuraDepartment of Human Neurosciences, Epilepsy Unit, Sapienza, University of Rome, Viale dell'Università 30, Rome, 00185, Italy.
Jerzy P SzaflarskiDepartments of Neurology, Neurosurgery, and Neurobiology, UAB Epilepsy Center, University of Alabama at Birmingham Heersink School of Medicine, 1670 University Blvd, Birmingham, AL, 35294, USA.
Laura E Hernández-VanegasDepartment of Clinical Research, Epilepsy Clinic, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877, Mexico, 14269, Mexico.
Monica L Moya-AlfaroDepartment of Clinical Research, Epilepsy Clinic, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877, Mexico, 14269, Mexico.
Yingying ZhangDepartment of Neurology, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610000, China.
Dong ZhouDepartment of Neurology, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610000, China.
Nicola PietrafusaDepartment of Neuroscience, Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, 00165, Italy.
Nicola SpecchioDepartment of Neuroscience, Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, 00165, Italy.
Giorgi JaparidzeDepartment of Clinical Neurophysiology, Institute of Neurology and Neuropsychology, 83/11 Vazha-Pshavela Ave., Tbilisi, 186, Georgia.
Sándor BeniczkyDepartment of Clinical Neurophysiology, Danish Epilepsy Centre, Filadelfia, Visby Allé 5, Dianalund, 4293, Denmark.
Mubeen JanmohamedDepartment of Neurosciences, Central Clinical School, Monash University, 99 Commercial Road, Melbourne, Victoria, 3004, Australia.
Patrick KwanDepartment of Neurosciences, Central Clinical School, Monash University, 99 Commercial Road, Melbourne, Victoria, 3004, Australia.
Marte SyvertsenDepartment of Neurology, Vestre Viken Hospital Trust, Dronninggata 28, Drammen, 3004, Norway.
Kaja K SelmerNational Centre for Epilepsy & Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, G. F. Henriksens vei 29, Sandvika, 1337, Norway.
Bernd J VorderwülbeckeDepartment of Neurology, Epilepsy-Center Berlin-Brandenburg, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
Martin HoltkampDepartment of Neurology, Epilepsy-Center Berlin-Brandenburg, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, 10117, Germany.
Lakshminarayanapuram G ViswanathanDepartment of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India.
Sanjib SinhaDepartment of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 560029, India.
Betül BaykanDepartment of Neurology and Clinical Neurophysiology, Istanbul Faculty of Medicine, Istanbul University, Millet Cad, Istanbul, 34390, Turkey.
Ebru AltindagDepartment of Neurology, Istanbul Florence Nightingale Hospital, Abide-i Hürriyet Cad, Istanbul, 34381, Turkey.
Felix von PodewilsDepartment of Neurology, Epilepsy Center, University Medicine Greifswald, Sauerbruchstraße, Greifswald, 17489, Germany.
Juliane SchulzDepartment of Neurology, Epilepsy Center, University Medicine Greifswald, Sauerbruchstraße, Greifswald, 17489, Germany.
Udaya SeneviratneDepartment of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, 55 Victoria Parade, Melbourne, Victoria, 3065, Australia.
Alejandro Viloria-AlebesqueDepartment of Neurology, Hospital General de la Defensa, Vía Ibérica 1, Zaragoza, 50009, Spain.
Ioannis KarakisDepartment of Neurology, Emory University School of Medicine, 49 Jesse Hill Jr. Drive SE, Office 335, Atlanta, GA, 30303, USA.
Wendyl J D'SouzaDepartment of Medicine, St Vincent's Hospital Melbourne, The University of Melbourne, 55 Victoria Parade, Melbourne, Victoria, 3065, Australia.
Josemir W SanderDepartment of Neurology, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu, 610000, China.
Bobby P C KoelemanDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
Willem M OtteDepartment of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
Kees P J BraunDepartment of Child Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, European Reference Network EpiCARE, Heidelberglaan 100, Utrecht, 3584 CX, Netherlands.
University of Southern Denmark · DKNational Hospital for Neurology and Neurosurgery · GBEmory University · USHeidelberg University · DESichuan University · CNInstituto de Investigación Sanitaria Aragón · ESIstanbul Florence Nightingale Hospital · TRThe University of Melbourne · AUUniversitätsmedizin Greifswald · DEAarhus University Hospital · DKBambino Gesù Children's Hospital · ITInstituto Nacional de Neurología y Neurocirugía · MXNeurological Research Institute · USOslo University Hospital · NOShiraz University of Medical Sciences · IRThe Royal Melbourne Hospital · AUThomas Jefferson University · USUniversity of Alabama at Birmingham · USUniversity of Luxembourg · LUVestre Viken Hospital Trust · NO

Funding

EEG-fMRI in Patients with JMEK23NS052468 · NINDS · UNIVERSITY OF CINCINNATI · PI SZAFLARSKI, JERZY P · 2006 to 2010
$869k
NINDS NIH HHS K23 NS052468
6 · The paper itself

Abstract

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.

Indexed as

Drug resistanceIndividual participant dataJMEJuvenile myoclonic epilepsyMedication withdrawalMeta-analysisMultivariable predictionPrediction modelRefractory epilepsyRemissionSeizure recurrence

Identifiers

PMID36467455
PMCPMC9716332
OpenAlexW4308929805

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.