OS11.5.A Utility of lumbar puncture (LP) and cerebrospinal fluid (CSF) profile in the diagnosis of neoplastic meningitis (NM): a retrospective cohort study and meta-analyses

Abstract

Abstract Background CSF cytology remains the gold standard for diagnosing NM, but the sensitivity of this test is low (approximately 50% with one LP). Little is known about the predictive value of routine CSF and clinical findings for a positive cytology. We addressed these questions by analyzing 337 consecutive patients at our institution, and by conducting exhaustive evidence-based literature reviews and meta-analyses of relevant research. Material and Methods 337 consecutive patients at a single institution were evaluated. Of these, 210 met criteria for NM (a positive CSF cytology on at least one of four pre-treatment samples) or no NM (four consecutive negative CSF cytologies). CSF white blood cell count, glucose, protein, and lactate were collected, as well as the presence of neurological symptoms. Optimal threshold values were identified using ROC curves. Sensitivity (Sn), specificity (Sp), and likelihood ratios were calculated for each variable. Two PRISMA-compliant meta-analyses were also performed: one analyzed studies reporting the cytology results of multiple LPs, and one analyzed the frequency of abnormal CSF findings as predictors of NM. Results All published results describe outcomes in patients with known NM. These results are, therefore, strongly distorted by spectrum bias, which artificially inflates the apparent sensitivity and specificity of those outcomes. Thus, 25 studies report the yield of positive CSF cytology on the first, second, and third LP as 73%, 87%, and 94%, but also do not describe the parameters of the procedure. Our series in patients with suspected NM (the cohort most relevant to the practicing physician) reports 74%, 85%, and 92% for immediately processed, 10 mL or greater, lumbar and ventricular specimens. Similarly, while 50 studies suggested that low CSF glucose, high CSF protein, and suggestive symptoms are associated with NM, we found very poor Sn/Sp for elevated protein (61%/61%), low glucose (35%/85%), elevated lactate (35%/91%), and symptoms consistent with NM (74%/73%). Of these values, only an elevated lactate and symptoms were even marginally helpful in predicting a positive CSF cytology. No variable predicted a negative cytology, and 22.8% of patients with a positive CSF cytology had completely normal CSF findings. Conclusion Generally accepted concepts about the frequency of CSF and clinical findings in patients with suspected NM are based on biased estimates in the literature. No CSF chemistry or clinical finding reliably predicts the presence of NM, and almost a quarter of patients with cytologically proven NM have completely normal findings. In patients with positive CSF cytologies, about 73% are detected after one LP, and more than 90% after 3, but again these findings represent overestimates because of pervasive spectrum bias and differences in sample acquisition/handling. Better diagnostic techniques are desperately needed.