Prevalence of Cerebrospinal Fluid Abnormalities in First Episode Psychosis: A Systematic Review and Meta-analysis

ImportanceFirst-episode psychosis (FEP) may result from a variety of secondary etiologies, making lumbar puncture (LP) for cerebrospinal fluid (CSF) investigations an important diagnostic consideration in this context. However, the lack of high-quality evidence on the prevalence of clinically-relevant CSF abnormalities hampers clinical consensus on when to pursue LP in FEP. ObjectiveDetermine a meta-analytic estimate of the prevalence of clinically-relevant CSF abnormalities in FEP. Data SourcesElectronic databases Ovid, Medline, Embase, PsychoINFO, and Web of Science were searched from inception to October, 2024. References of included articles were also screened. Study SelectionWe included studies that performed LP on a cohort of FEP and reported results of clinically available CSF analysis, enabling prevalence-estimates of abnormalities. Data Extraction and SynthesisData was extracted following PRISMA and MOOSE guidelines. Pooled prevalences were calculated by random-effects models. Moderators were tested using meta-regression analysis, and heterogeneity assessed by I2 index. Main Outcomes and MeasuresPrevalence of CSF abnormalities, focusing on clinically-relevant markers and number needed to assess (NNA). ResultsThirty-seven papers comprising 3,330 FEP patients who underwent LP were included, allowing calculation of prevalence-estimates for 12 CSF abnormalities. Of clinically-relevant abnormalities, the prevalence of CSF-restricted oligoclonal bands (OCB2) was 7.1% (95% CI 3.3-12.0, NNA 14), pleocytosis was 3.2% (95% CI 2.1-4.4, NNA 31) and anti-NMDAR antibodies was 2.3% (95% CI 0.1-6.4, NNA 43). Subgroup analysis showed that anti-neuronal antibodies were mainly detected in studies that selected patients with high suspicion of secondary causes and were low in studies which excluded patients with a high index of suspicion of a secondary cause, based on clinical and ancillary testing. OCBs and pleocytosis also had higher prevalence in the high-suspicion subgroup but were still detected at prevalence even in the low-suspicion subgroup. Conclusions and RelevanceThe meta-analytic estimate of the prevalence of the most common clinically relevant CSF abnormality was 7.1%, which is similar to the prevalence of finding any clinically-relevant radiologic abnormality with an MRI brain. Subgroup-analysis supports the usefulness of methods to estimate the pre-LP probability of clinically-relevant CSF abnormalities, albeit these methods are better applied for some abnormalities (CNS-reactive antibodies) than others (OCB2). Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of clinically actionable cerebrospinal fluid abnormalities in first-episode psychosis (FEP)? FindingsIn this systematic review and meta-analysis including 3330 patients with FEP who systematically received a lumbar puncture, at least 7.1% had a clinically-relevant abnormality detected in the cerebrospinal fluid; prevalence of oligoclonal bands was 7.1%, pleocytosis was 3.2%, anti-NMDAR antibodies were 2.3%, and other anti-neuronal antibodies were 0.4%. Subgroup-analysis identified association between prior suspicion of secondary causes and prevalence-estimates. MeaningLumbar puncture detects clinically-relevant abnormalities in FEP at a similar rate to brain MRI and may be especially informative when there is heightened suspicion for secondary psychosis.