Blood Biomarkers for the Diagnosis of Peripheral Causes of Vestibular Syndrome: A Systematic Review and Meta-Analysis

BACKGROUND: Peripheral vestibular syndromes (PVS) encompass disorders such as benign paroxysmal positional vertigo, vestibular neuritis, and Ménière's disease, presenting with vertiginous symptoms. Existing diagnostic approaches rely on clinical and vestibular function tests but have overlapping presentations and invasive investigations. Blood-based biomarkers may offer a minimally invasive diagnostic alternative.

OBJECTIVES: This systematic review and meta-analysis aims to synthesize current evidence on blood-based biomarkers to identify PVS compared with controls.

METHODS: A literature search was conducted for studies until January 1, 2025, in PubMed, Ovid Medline, and EMBASE databases analyzing blood-based biomarkers for PVS versus controls. The QUADAS-2 assessed study quality and a meta-analysis was conducted on biomarkers reported by at least two studies. Pooled standardized mean differences (SMD) with 95% confidence intervals were calculated, and heterogeneity was assessed using the I2 statistic.

RESULTS: Thirty-four studies (2,857 PVS, 3,249 controls) met the inclusion criteria where 75 biomarkers were identified and 31 meta-analyzed. Significant differences between PVS and controls were identified for otolin-1 (SMD, 1.53; 95% CI, 0.95 to 2.12), 25-OH vitamin D (SMD, -0.47; 95% CI, -0.76 to -0.19), C-reactive protein (SMD, 0.86; 95% CI, 0.35 to 1.37), leukocyte counts (SMD, 0.45; 95% CI, 0.18 to 0.72), neutrophil counts (SMD, 0.85; 95% CI, 0.44 to 1.25), and the neutrophil-to-lymphocyte ratio (SMD, 0.80; 95% CI, 0.48 to 1.12).

CONCLUSIONS: Inner ear-specific protein (otolin-1) and inflammatory markers (e.g., CRP, fibrinogen, leukocyte/neutrophil counts, and NLR) demonstrated potential diagnostic utility for PVS. Larger, prospective studies should confirm these findings, establish normative values, and explore combined biomarker panels to enhance diagnostic accuracy in PVS.