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Background and aims Seronegative autoimmune encephalitis is a heterogeneous entity characterised by the subacute onset of neurological symptoms and signs in association with paraclinical evidence of neuroinflammation but the absence of any known encephalitis-associated autoantibodies. The lack of specific biomarkers has led to clinical uncertainty regarding treatment and prognostication in seronegative autoimmune encephalitis. In this project, we aimed to address this knowledge gap.Methods We performed a systematic review and individual patient meta-analysis of published cases of seronegative autoimmune encephalitis between 2014 and 2024 (PROSPERO ID CRD42024555388) and supplemented this with our own local case data. We used univariate and mulitvariate analysis along with dimensionality reduction and clustering to identify key clinical and paraclinical features within the data associated with immunotherapy responsiveness and clinical outcome.Results We obtained individual case data on a total of 226 patients. We characterised key aspects of heterogeneity and demonstrated an association between time to immunotherapy and clinical outcome. We used multivariate regression analysis to identify candidate clinical and paraclinical markers of poor outcome.Conclusions Our study has highlighted the importance of prompt immunotherapy in seronegative autoimmune encephalitis and identified key factors associated with a poor outcome in this patient group.adam.handel@ndcn.ox.ac.uk