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Paediatric UK demyelinating disease longitudinal study (PUDDLS)
Michael Absoud1, Carole Cummins, Wui K Chong
1School of Health & Population Sciences, University of Birmingham, Birmingham, UK. michaelabsoud@childdemyelination.org.uk
Insights
Childhood Multiple Sclerosis (MS) studies can predict future trends in adult MS epidemiology. Researching early demyelinating events in children offers insights into MS pathogenesis and environmental factors.
Area of Science:
- Neurology
- Epidemiology
- Pediatrics
Background:
- Childhood Multiple Sclerosis (MS) accounts for at least 5% of cases, with diagnosis following a second demyelinating event.
- Changes in adult MS incidence and sex ratios, along with higher risk in children of immigrants, suggest pediatric cohorts may indicate emerging trends.
- Studying pediatric MS from the first demyelinating event can test hypotheses on changing epidemiology and inform understanding of MS pathogenesis.
Purpose of the Study:
- To establish the natural history, predictors, and outcomes of childhood central nervous system (CNS) inflammatory demyelinating diseases.
- To create a prospective, longitudinal cohort of children experiencing their first CNS inflammatory demyelinating event for long-term follow-up.
- To build a biological sample archive for future research, including biomarker validation, and to facilitate international collaboration.
Main Methods:
- The Paediatric UK Demyelinating Disease Longitudinal Study (PUDDLS) is a prospective, longitudinal observational study.
- Recruitment of children with a first CNS inflammatory demyelinating event across UK centers over approximately 5 years.
- Establishment of a biological sample archive (CSF, serum, DNA) and consent for future contact, alongside international collaboration and data sharing.
Main Results:
- The study is designed to capture the initial phase of pediatric demyelinating disease.
- It aims to identify predictors and outcomes for childhood CNS inflammatory demyelinating diseases.
- The PUDDLS cohort will enable validation of novel biomarkers and investigation of genetic and environmental interactions in MS.
Conclusions:
- Pediatric MS populations may represent early indicators of epidemiological shifts observed in adult MS.
- The early disease window in children provides a unique opportunity to study MS pathogenesis.
- Investigating childhood demyelinating events can yield insights into the changing epidemiology and etiology of Multiple Sclerosis.
Background:
There is evidence that at least 5% of Multiple sclerosis (MS) cases manifest in childhood. Children with MS present with a demyelinating episode involving single or multiple symptoms prior to developing a second event (usually within two years) to then meet criteria for diagnosis. There is evidence from adult cohorts that the incidence and sex ratios of MS are changing and that children of immigrants have a higher risk for developing MS. A paediatric population should reflect the vanguard of such changes and may reflect trends yet to be observed in adult cohorts. Studying a paediatric population from the first demyelinating event will allow us to test these hypotheses, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS.
Methods/Design:
The Paediatric UK Demyelinating Disease Longitudinal Study (PUDDLS) is a prospective longitudinal observational study which aims to determine the natural history, predictors and outcomes of childhood CNS inflammatory demyelinating diseases. PUDDLS will involve centres in the UK, and will establish a cohort of children affected with a first CNS inflammatory demyelinating event for long-term follow up by recruiting for approximately 5 years. PUDDLS will also establish a biological sample archive (CSF, serum, and DNA), allowing future hypothesis driven research. For example, the future discovery of a biomarker will allow validation within this dataset for the evaluation of novel biomarkers. Patients will also be requested to consent to be contacted in the future. A secondary aim is to collaborate internationally with the International Paediatric Multiple Sclerosis Study Group when future collaborative studies are proposed, whilst sharing a minimal anonymised dataset. PUDDLS is the second of two jointly funded studies. The first (UCID-SS) is an epidemiological surveillance study that already received ethical approvals, and started on the 1st September 2009. There is no direct patient involvement, and UCID-SS aims to determine the UK and Ireland incidence of CNS inflammatory demyelinating disorders in children under 16 years.
Discussion:
A paediatric population should reflect the vanguard of MS epidemiological changes and may reflect trends yet to be observed in adult MS cohorts. The restricted window between clinical expression of disease and exposure to environmental factors in children offers a unique research opportunity. Studying a paediatric population from the first demyelinating event will allow us to investigate the changing epidemiology of MS, and may offer further valuable insights into the genetic and environmental interactions in the pathogenesis of MS.
