Serum microRNA profile and serum neuron specific enolase, S-100, and interleukin-6 level as biomarkers for differentiating acute vertigo between cerebellar or brainstem infarction and peripheral vertigo

Abstract

Background and PurposeAcute vertigo is a common presentation of inner ear disease. However, it can also be caused by more serious conditions, especially posterior circulation stroke. Differentiation between these 2 conditions by clinical presentations and imaging studies during acute phase can be challenging. This study aims to evaluate the serum microRNA profile and serum neuron specific enolase (NSE), S-100, and interleukin-6 (IL-6) level as potential biomarkers to differentiate between patients with central vertigo due to cerebellar or brainstem infarction and peripheral vertigo.MethodsIn the discovery phase, miRNA expression profiling was performed by Nanostring nCounter Technology in serum of patients with central vertigo due to cerebellar or brainstem infarction (n=3) and peripheral vertigo (n=3) during acute phase within 72 hours after vertigo onset (day 0) and on day 90. MiRNAs that expressed only in acute phase of patients with stroke were selected as potential candidates. Subsequent validation was performed by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in the serum of patients with posterior circulation stroke (n=23) and peripheral vertigo (n=35). The serum NSE, S100 and interleukin-6 (IL-6) measurements were performed by electrochemiluminescence immunoassay (ECLIA).ResultsIn the discovery phase, miR-342-3p, miR-376-3p, and miR-433-5p were identified by Nanostring nCounter Technology as potential biomarker candidates. In subsequent validation phase, serum miR-433-5p was the only miRNA expressed at significantly high levels in patients with central vertigo during acute phase (median (IQR) central: 92.13 (49.06-183.2) copies/µL vs. peripheral: 53.45 (35.37-102.3) copies/µL, P=0.0056). Only miR-433-5p had discriminative ability to differentiate between central and peripheral vertigo with area under the receiver operating characteristic curve (AUROC) of 0.71. Using a serum miR-433-5p cut off at level >46 copies/µL, the sensitivity and specificity were 87% and 49% respectively. Both S100 (central: 0.111 (0.049-0.335) µg/L vs. peripheral: 0.054 (0.039-0.082) µg/L, P=0.005), and IL-6 central: 7.42 (4.23-14.47) pg/mL vs. peripheral: 2.44 (0.70-4.68) pg/mL, P< 0.001) had significantly higher level in patients with central vertigo.ConclusionThis is the first study to demonstrate the potential of serum miR-433-5p as a biomarker to differentiate between cerebellar or brainstem infarction and peripheral vertigo among patients with acute vertigo.