Translating metagenomics into clinical practice of complex paediatric neurological presentations

• DOI: 10.1101/2023.06.02.23290816
• Publication Date: 2023-06-05T17:55:19Z
• Authors: Justin Penner; Jane Hassell; Julianne R Brown; Kshitij Mankad; Nathaniel Storey; Laura Atkinson; Nisha Ranganathan; Alexander Lennon; Jack C D Lee; Dimitrios Champsas; Angelika Kopec; Divya Shah; Cristina Venturini; Garth Dixon; Surjo De; James Hatcher; Kathryn Harris; Kristian Aquilina; Maaike A. Kusters; Karyn Moshal; Delane Shingadia; Austen JJ Worth; Giovanna Lucchini; Ashirwad Merve; Thomas S Jacques; Alasdair Bamford; Marios Kaliakatsos; Judith Breuer; Sofia Morfopoulou
• Keywords: Etiology; Brain biopsy; Clinical Practice; Work-up

ABSTRACT Background Atypical or complex paediatric neurological presentations are common clinical conundrums and often remain undiagnosed despite extensive investigations. This is particularly pronounced in immunocompromised patients. Here we show that metagenomics (CMg) a valuable adjunct diagnostic tool to be used by neuro-infection multidisciplinary teams (MDTs). Methods We included patients referred the Great Ormond Street Hospital MDT whom uncertainty remained, standardised comprehensive set of investigations, who were for untargeted CMg on brain tissue and/or cerebrospinal fluid (CSF). In retrospective review, two clinicians independently assessed whether conjunction with resulted change management. Findings 60 met inclusion criteria. detected causative pathogen 14/60 (23%), 12/36 known immunocompromised. results, even when negative, informed patient care, resulting changes management 42/57 (74%). Six had unexpected findings pathogens not identified prior samples. four patients, was found solely biopsy absent from all other specimens, including CSF. Interpretation useful conventional techniques meningoencephalitis exhausted proved an important provided increased reassurance against infective aetiology recommending immunosuppressive immunomodulatory treatment. Specialised MDTs should advocate early biopsies routine experienced laboratory cases affecting