Mid-Regional Proadrenomedullin in Cerebrospinal Fluid Is a Reliable Diagnostic and Prognostic Marker for Acute Meningoencephalitis and Neurological Disorders

Objectives: Despite numerous pieces of evidence of its important role as a diagnostic and prognostic biomarker in infectious diseases and sepsis, adrenomedullin (ADM) was only poorly investigated in cerebrospinal fluid (CSF) in central nervous system (CNS) infections. In this multicentre retrospective study, we investigated ADM CSF concentrations in acute meningitis compared to other noninfectious neurological disorders. Methods: Since ADM is rapidly metabolised in vivo, the available diagnostic methods are designed to measure its cognate metabolite called mid-regional proADM (MR-proADM). We collected detailed clinical and laboratory data about 293 patients in whom MR-proADM was measured in CSF and plasma as part of the diagnostic workup. Results: Patients were finally classified in CNS infection (n = 59), other CNS disorders (n = 190) and 14 disease controls, in which CNS infections and other definite disorders were excluded. Both cerebrospinal MR-proADM levels and their CSF/blood ratio were significantly higher in CNS infections compared to the other two groups (p < 0.001 and p < 0.037 respectively). CSF MR-proADM resulted informative for patients' classification, furnishing a volume under the ROC surface of 0.513 [0.414–0.613], overcoming the 1/6 threshold value for undecidability. Threshold values of < 0.807 and > 1.590 nmol/L can differentiate controls from neurological disorders and neurological disorders from CNS infections respectively. Conclusions: We demonstrated significant upregulation of Adrenomedullin in CSF during infections compared to other neurological diseases and proposed preliminary thresholds of CSF MR-proADM to be used in the diagnostic workup of acute CNS infections, to help with differential diagnosis and possibly guide targeted therapeutic interventions.