# Exploring the Role of Cerebrospinal Fluid and Serum Mid-Regional Pro-Adrenomedullin in Tick-Borne Encephalitis: A Pilot Study

## TL;DR

This study explores MR-proADM as a potential biomarker for tick-borne encephalitis, finding altered levels in cerebrospinal fluid and serum that may indicate CNS infection and blood-CSF barrier dysfunction.

## Contribution

The study is the first to investigate MR-proADM in tick-borne encephalitis, revealing its potential as a biomarker for CNS infection and blood-CSF barrier dysfunction.

## Key findings

- Serum MR-proADM levels were significantly lower in TBE patients compared to controls.
- The CSF/serum MR-proADM ratio showed strong diagnostic performance with high sensitivity and specificity.
- CSF MR-proADM correlated with total CSF protein, indicating blood-CSF barrier dysfunction.

## Abstract

Background: Adrenomedullin (ADM) is a multifunctional peptide with vasoregulatory, antimicrobial, and anti-inflammatory properties. Its stable fragment, mid-regional pro-adrenomedullin (MR-proADM), is a validated biomarker in sepsis and systemic infections, but its role in viral neuroinfections remains unexplored. Tick-borne encephalitis (TBE), caused by the tick-borne encephalitis virus (TBEV), is a major viral infection of the central nervous system (CNS) associated with long-term neurological sequelae. This study aimed to assess MR-proADM levels in cerebrospinal fluid (CSF) and serum of patients with TBE and to evaluate their diagnostic utility and pathophysiological significance. Methods: This retrospective observational study included 20 patients with confirmed TBE and 14 non-infectious neurological controls. MR-proADM concentrations were measured in paired CSF and serum samples using an ELISA assay. Statistical analyses included group comparisons (Mann–Whitney U test), correlation analyses (Spearman’s r), and receiver operating characteristic (ROC) curve evaluation. Results: Serum MR-proADM levels at baseline (SER1) were significantly lower in TBE patients compared with controls (p = 0.0197). The CSF/serum MR-proADM ratio differed significantly between groups (p = 0.0063) and showed the best diagnostic performance (AUC = 0.816, 95% CI 0.63–0.93; sensitivity 79%, specificity 80%). MR-proADM concentrations in CSF correlated with total CSF protein (r = 0.53), suggesting an association with blood–CSF barrier dysfunction. Strong reproducibility was observed for serum MR-proADM between sampling points (r = 0.83). Conclusions: MR-proADM levels in CSF and serum are altered in patients with TBE, indicating its potential as a biomarker of CNS infection and inflammation. The CSF/serum MR-proADM ratio may serve as a sensitive indicator of blood–CSF barrier involvement, while decreased serum levels may reflect impaired systemic neuroprotective response. These findings highlight a possible role of ADM in neuroimmune regulation during viral encephalitis and warrant validation in larger prospective studies.