Exploring the relationships between composite scores of disease severity, seizure-freedom and quality of life in Dravet syndrome.

Composite endpoint Dravet syndrome Quality of life Seizures Statistical analysis Symptoms

Journal

Neurological research and practice
ISSN: 2524-3489
Titre abrégé: Neurol Res Pract
Pays: England
ID NLM: 101767802

Informations de publication

Date de publication:
06 Jun 2022
Historique:
received: 10 04 2022
accepted: 02 05 2022
entrez: 6 6 2022
pubmed: 7 6 2022
medline: 7 6 2022
Statut: epublish

Résumé

In Dravet syndrome (DS), a rare epileptic and developmental encephalopathy, the effectiveness of a new treatment is predominantly measured in terms of seizure frequency. However, this may not fully capture the impact of a treatment on the broader aspects of the syndrome and patients' health-related quality of life (HRQoL). Using a previously published survey which collected data from DS patients and their carers on the broader manifestations of their syndrome, their HRQoL, and their experience of seizures, this study created composite measures of symptom severity to offer new perspectives on the multifaceted aspects of this rare condition. Survey responses on the severity of physical and psychosocial symptoms were combined with independent assessments of disability and care need, to generate three composite symptom scores assessing the manifestations of DS (physical, psychosocial and care requirements). Variation in HRQoL was investigated in multiple regression analyses to assess the strength of association between each of these composite measures and three forms of seizure measures (seizure frequency, days with no seizures and longest interval without seizures), as experienced over a 4- and 12-week period. Composite scores were calculated for a cohort of 75 primarily paediatric patients who were enrolled in the study. Strong associations were found between each of the three composite symptom scores and each of the three seizure measures, with the regression coefficient on symptom score highly significant (p ≤ 0.001) in all nine comparisons. Separate regressions using predictors of HRQoL (Kiddy KINDL and Kid KINDL) as the dependent variable were inconclusive, identifying only behavioural/attention problems and status epilepticus as significant predictors of HRQoL. These results allow the development of a composite score that may be useful in developing a clinical understanding of the severity of DS for an individual patient and establishing their treatment goals. Where measurement of long-term sequalae of disease is not feasible, such as clinical trials, correlation of the composite score with experience of seizures and seizure-free periods may allow a better contextualisation of the results of short-term assessments. German Clinical Trials Register (DRKS), DRKS00011894. Registered 16 March 2017, http://www.drks.de/ DRKS00011894.

Sections du résumé

BACKGROUND BACKGROUND
In Dravet syndrome (DS), a rare epileptic and developmental encephalopathy, the effectiveness of a new treatment is predominantly measured in terms of seizure frequency. However, this may not fully capture the impact of a treatment on the broader aspects of the syndrome and patients' health-related quality of life (HRQoL). Using a previously published survey which collected data from DS patients and their carers on the broader manifestations of their syndrome, their HRQoL, and their experience of seizures, this study created composite measures of symptom severity to offer new perspectives on the multifaceted aspects of this rare condition.
METHODS METHODS
Survey responses on the severity of physical and psychosocial symptoms were combined with independent assessments of disability and care need, to generate three composite symptom scores assessing the manifestations of DS (physical, psychosocial and care requirements). Variation in HRQoL was investigated in multiple regression analyses to assess the strength of association between each of these composite measures and three forms of seizure measures (seizure frequency, days with no seizures and longest interval without seizures), as experienced over a 4- and 12-week period.
RESULTS RESULTS
Composite scores were calculated for a cohort of 75 primarily paediatric patients who were enrolled in the study. Strong associations were found between each of the three composite symptom scores and each of the three seizure measures, with the regression coefficient on symptom score highly significant (p ≤ 0.001) in all nine comparisons. Separate regressions using predictors of HRQoL (Kiddy KINDL and Kid KINDL) as the dependent variable were inconclusive, identifying only behavioural/attention problems and status epilepticus as significant predictors of HRQoL.
CONCLUSIONS CONCLUSIONS
These results allow the development of a composite score that may be useful in developing a clinical understanding of the severity of DS for an individual patient and establishing their treatment goals. Where measurement of long-term sequalae of disease is not feasible, such as clinical trials, correlation of the composite score with experience of seizures and seizure-free periods may allow a better contextualisation of the results of short-term assessments.
TRIAL REGISTRATION BACKGROUND
German Clinical Trials Register (DRKS), DRKS00011894. Registered 16 March 2017, http://www.drks.de/ DRKS00011894.

Identifiants

pubmed: 35659154
doi: 10.1186/s42466-022-00186-9
pii: 10.1186/s42466-022-00186-9
pmc: PMC9169336
doi:

Types de publication

Journal Article

Langues

eng

Pagination

22

Informations de copyright

© 2022. The Author(s).

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Auteurs

Adam Strzelczyk (A)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany. strzelczyk@med.uni-frankfurt.de.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany. strzelczyk@med.uni-frankfurt.de.
Epilepsy Center Hessen and Department of Neurology, Philipps-University Marburg, Marburg (Lahn), Germany. strzelczyk@med.uni-frankfurt.de.

Gerhard Kurlemann (G)

Department of Neuropediatrics, University of Münster, Münster, Germany.

Thomas Bast (T)

Epilepsy Center Kork, Kehl-Kork, Germany.
Faculty of Medicine, University of Freiburg, Freiburg i. Br., Germany.

Ulrich Bettendorf (U)

Neuropediatric Practice, Hirschaid, Germany.

Gerhard Kluger (G)

Epilepsy Center for Children and Adolescents, Clinic for Neuropediatrics and Neurorehabilitation, Schön Klinik Vogtareuth, Vogtareuth, Germany.
Research Institute "Rehabilitation, Transition, and Palliation", PMU Salzburg, Salzburg, Austria.

Thomas Mayer (T)

Epilepsy Center Kleinwachau, Radeberg, Dresden, Germany.

Bernd A Neubauer (BA)

Department of Neuropediatrics, Justus-Liebig-University Giessen, Giessen, Germany.

Tilman Polster (T)

Epilepsy Center Bethel, Bielefeld, Germany.

Sarah von Spiczak (S)

Northern German Epilepsy Center for Children and Adolescents, Raisdorf, Kiel, Germany.

Regina Trollmann (R)

Department of Neuropediatrics, Friedrich-Alexander University, Erlangen, Germany.

Markus Wolff (M)

Department of Pediatric Neurology, Vivantes Klinikum Neukölln, Berlin, Germany.

Toby Toward (T)

Zogenix International Limited, Maidenhead, United Kingdom.

Jens Gruenert (J)

Zogenix International Limited, Maidenhead, United Kingdom.

Eddie Gibson (E)

Wickenstones Ltd., Abingdon, United Kingdom.

Clive Pritchard (C)

Wickenstones Ltd., Abingdon, United Kingdom.

Joe Carroll (J)

Wickenstones Ltd., Abingdon, United Kingdom.

Felix Rosenow (F)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.

Susanne Schubert-Bast (S)

Epilepsy Center Frankfurt Rhine-Main and Department of Neurology, Goethe-University Frankfurt, Schleusenweg 2-16 (Haus 95), 60528, Frankfurt am Main, Germany.
Center for Personalized Translational Epilepsy Research (CePTER), Goethe-University Frankfurt, Frankfurt am Main, Germany.
Department of Neuropediatrics, Goethe-University Frankfurt, Frankfurt am Main, Germany.

Classifications MeSH