Prevalence of clinically-relevant cerebrospinal fluid abnormalities in first-episode psychosis: a systematic review...

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.

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

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

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 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.

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

Thirty-seven papers comprising 3,330 FEP patients who underwent LP were included, allowing calculation of prevalence estimates for 14 clinically-available CSF abnormalities. The prevalence of CSF-restricted oligoclonal bands (OCB2) was 7.1% (95% CI 3.3-12.0, NNA 14), the prevalence of pleocytosis was 3.2% (95% CI 2.1-4.4, NNA 31) and the prevalence of anti-NMDAR antibodies was 2.3% (95% CI 0.1-6.4, NNA 43). Subgroup analysis found that the prevalence of anti-NMDAR antibodies was higher in studies that selected for patients with a high index of suspicion of secondary causes compared to studies which excluded these patients, based on clinical and ancillary testing. OCBs and pleocytosis were detected at appreciable prevalence in both the high-suspicion and low-suspicion subgroups.

The most common clinically-relevant CSF abnormality, CSF-restricted oligoclonal bands, had a pooled prevalence of 7.1%, similar to the reported prevalence of a clinically-relevant abnormality on brain MRI. The probability of detecting an abnormality was higher among patients with a high index of suspicion for a secondary cause, and this was most marked for anti-NMDAR antibodies. However, few studiesincluded healthy controls, and none explicitly reported whether the presence of these abnormalities altered treatment response or outcomes. Further research is therefore needed to establish the specificity and treatment implications of these findings.