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

Importance

First-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.

Objective

Determine a meta-analytic estimate of the prevalence of clinically-relevant CSF abnormalities in FEP.

Data Sources

Electronic databases Ovid, Medline, Embase, PsychoINFO, and Web of Science were searched from inception to October, 2024. References of included articles were also screened.

Study Selection

We 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 Synthesis

Data 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 I ² index.

Main Outcomes and Measures

Prevalence of CSF abnormalities, focusing on clinically-relevant markers and number needed to assess (NNA).

Results

Thirty-eight papers comprising 3,552 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 bans (OCB2) was 6.5% (95% CI 3.1-10.8, NNA 15), 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 Relevance

The meta-analytic estimate of the prevalence of the most common clinically relevant CSF abnormality was 6.5%, 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 Points

Question: What is the prevalence of cerebrospinal fluid abnormalities in first-episode psychosis (FEP)?

Findings: In this systematic review and meta-analysis including 3,552 patients with FEP who systematically received a lumbar puncture, at least 6.5% had a clinically-relevant abnormality in the cerebrospinal fluid; prevalence of oligoclonal bands was 6.5%, 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.

Meaning: Lumbar 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.