Safety and Diagnostic Utility of Brain Biopsy and Metagenomics in Decision-Making for Patients with Inborn Errors of Immunity (IEI) and Unexplained Neurological Manifestations

Unexplained neurological symptoms can pose a diagnostic challenge in patients with inborn errors of immunity (IEI) where the aetiology can be varied, and diverse pathologies may require contrasting treatments. Brain biopsy, the process of sampling brain tissue directly, has historically provided histological and microbiological information and can now be exploited for deep metagenomic next generation analysis (mNGS). We conducted a retrospective analysis of clinical and diagnostic data on paediatric patients with IEI who had a brain biopsy between 2010 and 2022 at a UK tertiary centre where 14 patients fulfilled our search criteria. We report on clinical characteristics, adverse events and the additional impact of mNGS of brain biopsies, where these were conducted. We found that brain biopsy enabled diagnostics with manageable complications in most cases, either by tissue or metagenomics analysis (n = 11/14, 79%). We found that mNGS analysis improved the diagnostic yield of brain biopsy in 29% of IEI cases (n = 4/14). Brain biopsy enabled a change in management in 71% of cases (n = 10/14). This series provides compelling evidence for the safe and purposeful use of brain biopsy in children with IEI.