Anjali Chandra, Laura Duque, Andrew Pines, Anne Fladger, Giovanna S Manzano, Michael E Benros, Graham Blackman, Matthew L Baum
Thirty-seven papers comprising 3,330 FEP patients who underwent LP were included, allowing calculation of prevalence estimates for 14 clinically-available 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-NMDAR 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. OCB2 was detected at appreciable prevalence in both the high-suspicion and low-suspicion subgroups; a high-suspicion subgroup estimate could not be derived for pleocytosis.
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-available CSF abnormalities in FEP.
DATA SOURCES: Electronic databases Ovid MEDLINE, Embase, PsycINFO, 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 I2 index.
MAIN OUTCOMES AND MEASURES: Prevalence of clinically-available CSF abnormalities, focusing on clinically-relevant markers and number needed to assess (NNA).
RESULTS: Thirty-seven papers comprising 3,330 FEP patients who underwent LP were included, allowing calculation of prevalence estimates for 14 clinically-available 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-NMDAR 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. OCB2 was detected at appreciable prevalence in both the high-suspicion and low-suspicion subgroups; a high-suspicion subgroup estimate could not be derived for pleocytosis.
CONCLUSION AND RELEVANCE: 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 included studies reported healthy controls, and none explicitly tested whether presence of these abnormalities alter treatment response or outcomes, so the specificity and treatment implications of these findings for psychosis will benefit from future research.