Obtaining information from the brain in a non-invasive way: determination of iron in nasal exudate to differentiate hemorrhagic and ischemic strokes

Abstract

BackgroundDifferentiation between hemorrhagic and ischemic stroke is currently made by brain imaging or analyzing blood and cerebrospinal fluid (CSF) samples. After describing a new drainage route from brain to nasal mucosa, nasal exudate samples can be considered a new and promising source of biomarkers. Saliva can also be evaluated.MethodsWe determined iron in nasal exudate and saliva samples from patients of acute stroke during the first 48 h from onset. A simple, non-invasive sampling procedure was employed to obtain information from the brain. Samples were taken with a pre-weighed swab, solved in a 2% nitric acid solution and iron was measured by inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS).ResultsA significant difference in the dispersion of results of iron concentration for both stroke subtypes was observed in nasal exudate samples. The interquartile range was 0.608 nmol mg−1 of iron for hemorrhagic strokes and only 0.044 nmol mg−1 for ischemic strokes. In saliva samples, however, the values were 0.236 vs. 0.157 nmol mg−1. A cut-off limit of 0.102 nmol of iron per mg of nasal exudate provides a methodology with a 90% of sensitivity and a 90% of specificity. The value of the area under (AUC) the receiver operating characteristic curve (ROC) for nasal exudate samples is 0.960, considered as very good in which regards to its predictive value.ConclusionsNon-invasive samples of nasal secretion have allowed obtaining, for the first time, information from the brain. Determination of iron in nasal exudate by ICP-MS allowed differentiation between ischemic and hemorrhagic strokes.

Iron Measured in Nasal Exudate Samples as a New and Useful Biomarker in the Differential Diagnosis of Patients with Acute Stroke

“…Twenty of the study patients were included in a previous publication [16]; we found similar trends in subjects who did not take part of the previous study (nasal exudate iron concentration: 0.103 ± 0.010 nmol/mg in the IS group vs. 0.480 ± 0.050 nmol/mg in the HS group p < 0.0001). These concentration differences were not found in the levels of iron in blood (IS 58.38 mcg/dL and HS 66.05 mcg/dL p = 0.323).…”

“…The chance of studying cerebral lymphatic drainage opens up new expectations in this field. Our group performed a previous pilot study which suggested that measurement of iron in nasal secretion was feasible and could distinguish between IS and HS [16]. Our objective was to confirm our previous findings in a bigger sample of stroke patients.…”

“…This study included 32 patients with IS and 43 patients with HS ( Table 1). The first 20 patients (10 IS and 10 HS) were used to develop the methodology [16].…”

“…Nasal exudate samples were obtained within 48 h from symptom onset. Iron was determined following an analytical methodology previously optimized and characterized [16]. Briefly, samples were collected by the same researcher with Thermo Scientific TM swabs making circular movements in the area closest to the upper turbinate for 3 s in each nostril.…”

Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics

“…The authors were able to differentiate patients that had suffered from hemorrhagic stroke compared with ischemic stroke by the amount of iron in the nasal exudate. Although this study was preliminary, consisting of samples from only 20 patients, it serves as in vivo clinical evidence that CSF waste products may be cleared through nasal pathways, at least during pathological conditions [246].…”