Retrospective validation of a β-trace protein interpretation algorithm for the diagnosis of cerebrospinal fluid leakage

Abstract

Background: Cerebrospinal fluid (CSF) leakage is a rare condition that can potentially lead to the development of serious complications. In the last decade, β-trace protein (β-TP) has been shown to be a valuable immunological biomarker that allows prompt and non-invasive identification of CSF leakage. At our institution, the measurement of β-TP has been included in the diagnostic work-up of CSF leakage for more than 10 years. According to our diagnostic algorithm, the presence of CSF in secretion is excluded when β-TP values are <0.7 mg/L, whereas β-TP values ≥1.3 mg/L indicate the presence of CSF in secretion. β-TP values between 0.7 and 1.29 mg/L indicate the presence of CSF if the β-TP ratio (β-TP secretion/β-TP serum) is ≥2. This study aimed to validate this diagnostic algorithm using clinically defined nasal/ear secretions. Methods: We performed a retrospective statistical analysis of three β-TP interpretation strategies using data of 236 samples originating from 121 patients with suspect CSF leakage received at our laboratory between 2004 and 2012. Results: The highest odds ratio was obtained when the proposed algorithm has been used for the interpretation of β-TP results, showing a sensitivity of 98.3% and a specificity of 96%. Positive and negative predictive values were 89.2% and 99.4%, respectively.

Management and Outcomes of Spontaneous Cerebrospinal Fluid Otorrhoea

“…β-trace protein (βTP) testing was performed on fluid obtained from the affected ear and compared to the serum levels βTP, in line with the diagnostic algorithm of Bernasconi et al (18) The doctor's delay was defined as the time between the first presenting features of CSF leakage (chronic otorrhoea or meningitis) and the confirmed diagnosis of CSF leakage (positive βTP). Radiographic imaging consisted of multi-detector computed tomography of the temporal bone and magnetic resonance imaging.…”

“…Patients can also report other non-specific symptoms such as aural fullness, tinnitus, and a headache (1). Diagnosis is confirmed by β2transferrin or β-trace protein analysis in the fluid retracted from the ear (5,18,19); radiologic imaging before reconstructive surgery is primordial to inform the surgeon about the site, size, and consistency of the defect(s).…”

Tau protein as a possible marker of cerebrospinal fluid leakage in cerebrospinal fluid rhinorrhoea: A pilot study

“…β-trace protein (prostaglandin D2 synthase), a member of the family of lipocalins, is the second most abundant protein in CSF after albumin ( 12 , 13 ). β-trace protein is also measurable in healthy subject’s rhinorrhoea fluid.…”

Rapid Diagnostic Test Kit for Point-of-Care Cerebrospinal Fluid Leak Detection

“…15 As a result, numerous studies have demonstrated that nasal secretions with βTP concentrations (measured using laser nephelometry) above a certain threshold are highly likely to be contaminated with CSF. [16][17][18][19][20] A recent study by Bernasconi et al 21 demonstrated that concentrations of βTP in nasal secretions ≥1.3 mg/L indicate the presence of a CSF leak, whereas concentrations of βTP <0.7 mg/L indicate the absence of a leak. βTP concentrations between 0.7 and 1.29 mg/L (denoted the "gray zone") require further analysis and comparison with the patient's βTP serum level to confirm the presence or absence of a CSF leak.…”

“…Overall, this approach showed a sensitivity and specificity of 98.3% and 96%, respectively. 21 Although the nephelometric assay is more rapid than electrophoresis, it still requires centralized laboratory equipment that may not be available in every clinical setting. In fact, there are still no proven, widely available diagnostic techniques that allow physicians to rule out the presence of a CSF leak in a rapid, affordable, and noninvasive manner.…”