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Make a choice Coretta Van Leer Buter Jelte Helfferig Bert Niesters Marit de Lange Bart Jacobs

Project properties

Title	Acute flaccid paralysis in children: exploring methods to improve diagnostic accuracy
Keywords	virology Acute flaccid myelitis Guillain-Barré syndrome
Researchers	Coretta Van Leer Buter Jelte Helfferig Bert Niesters Marit de Lange Bart Jacobs
Type of project	Pilot project (year 2 or 3), Stage Wetenschap / Researchproject of MD/PhD programme
Nature of the research	Prospective multicenter study
Fields of study	pediatrics neurology virology

Background / introduction

Acute flaccid paralysis (AFP) is a syndrome of rapidly progressive limb weakness, that may have many different causes. In children, two important causes of AFP are acute flaccid myelitis, in which viruses damage the anterior horn cell the spinal cord and Guillain-Barré syndrome (GBS), an immune-mediated polyneuropathy. Both conditions are rare with approximately 2 children with AFM and 20 children with GBS per year in the Netherlands. However, the incidence may change as both conditions are associated with infections, which may be endemic, but may also occur in outbreaks. Polioviruses are the best known cause of AFM (poliomyelitis), but in the past ten years AFM has mostly been associated with non-polio enteroviruses, such as enterovirus D68 and A71. GBS is also mostly caused by infections, but has also been associated with vaccinations, potentially causing societal distress. Two themes will play a central role in this research: 1. There is often important diagnostic delay in children with AFP, which leads to suboptimal treatment and potentially persisting deficits in affected patients. Early and accurate diagnostic procedures could help in making the correct diagnosis, but evidence-based guidelines for AFP are currently not available. 2. The association between infections and different causes of AFP is incompletely elucidated. Clarification of this association provides opportunities for surveillance, diagnostic procedures and treatment and possibly prevention. After the completion and publication of the results from our retrospective study, in which all hospitals with a pediatric neurology department in the Netherlands participated, we are now in the process of starting a prospective national cohort study in children with AFP, coordinated by UMCG, in collaboration with important stakeholders such as the RIVM.

Research question / problem definition

Short-term (student) 1. To develop a diagnostic protocol for children with AFP 2. To take part in the set-up the study, including organization and data sharing 3. To collect data and obtain permissions from potential participants Long-term (MD-PhD) 4. To identify early clinical and diagnostic features that differentiate the conditions causing AFP. 5. To clarify the relation between infections and these conditions.

Workplan

The student will be involved in the development of the study protocol and set-up of the study, data collection, analysis of results and if possible, the writing of a manuscript for publication in one of the projects. Depending on the results of a project, participation can result in the development of a MD-PhD project. During the research project, the student is able to participate in ongoing meetings of the pediatric neurology and virology and can participate in the outpatient clinical follow-up.

References

1. J Helfferich, MM de Lange, KS Benschop et al. Epidemiology of acute flaccid myelitis in children in the Netherlands, 2014 to 2019; Euro Surveill. 2022 Oct;27(42):2200157. 2. J Helfferich, RF Neuteboom, MMA de Lange et al. Pediatric acute flaccid myelitis: Evaluation of diagnostic criteria and differentiation from other causes of acute flaccid paralysis. Eur J Paediatr Neurol. 2023 May;44:28-36. doi: 10.1016/j.ejpn.2023.03.002. 3. Murphy OC, Messacar K, Benson L, Bove R, Carpenter JL, Crawford T, et al. Acute flaccid myelitis: cause, diagnosis, and management. Lancet [Internet]. 2020 Dec 28; Available from: https://doi.org/10.1016/S0140-6736(20)32723-9 4. Hayes LH, Hopkins SE, Liu S, Pardo CA, Garcia-Dominguez MA, Oleszek J, et al. Challenges in the clinical recognition of acute flaccid myelitis and its implications. J Pediatr. 2022 Sep;