Nasal exudate for diagnosis of stroke: fundamental studies through iron fractionation, total iron, and targeted protein determinations.

During the last years, there has been an increasing research interest in the analysis of biological fluids requiring non-invasive sampling for biomedical and clinical applications. In this work, we have focused on the nasal exudate with the aim of investigating the potential use of this fluid to know the role of iron in stroke and also for diagnosis. Potential differences in the nasal exudate, collected in swabs, from diagnosed hemorrhagic stroke, ischemic stroke, and control groups were investigated with regard to total iron by inductively coupled plasma-mass spectrometry, iron fractionation studies by size exclusion chromatography together with post-column isotope dilution analysis, and four proteins containing iron (ferritin, transferrin, lactoferrin, and ferroportin) with ELISA kits. All these analyses represent an analytical challenge, considering the rather limited amount of sample (10-40 mg) available, being the nasal exudate extracted from the swab with 300 µL 10 mM Tris/HCl, pH = 7.4. Studies to obtain reliable analytical information, such as the blank contribution of the sampling step, evaluation of the extraction efficiency of the nasal exudate from the swab, and normalization strategies for data treatment, have been carried out. Results showed that despite the limited number of investigated samples, fractionation studies as well as the concentrations of ferritin and ferroportin obtained with ELISA kits showed a differential behavior between the different cohorts.

Measurement of GFAP in nasal exudate in the differential diagnosis between ischemic and hemorrhagic stroke.

INTRODUCTION: Differential diagnosis between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is a great challenge. Recently, the discovery of cerebral lymphatic drainage towards the nostrils suggested nasal exudate (NE) as a new source for measure biomarkers from neural damage. We sought to confirm whether glial fibrillary acidic protein (GFAP) levels in NE could identify ICH. METHODS: GFAP in nasal exudate (nGFAP) was studied in 5 IS and 5 ICH patients. All patients underwent neurological examination, brain computed tomography, laboratory tests and measurement of nGFAP and serum GFAP. RESULTS: We found higher concentrations in ICH patients (p=0.02). The area under the ROC curve for IS/ICH discrimination was 0.840, with a cut-off point of 0.06 pg/mg for 100% sensitivity and 80% specificity Conclusions: These findings suggest that nGFAP could be a useful biomarker for differential diagnosis between IS and ICH and opens a potential field of study for other biomarkers in NE in neurological disorders.

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

INTRODUCTION: Differential diagnosis between ischemic and hemorrhagic strokes in the acute stage is one of the major challenges of neurovascular research. Several biomarkers have been studied, but attempts to date have focused on determining their blood levels. Recently, cerebral lymphatic drainage toward the nostrils has been discovered, giving us the chance to study nasal exudate looking for biomarkers of neural damage. We sought to confirm whether iron levels in nasal exudate could identify the hemorrhagic nature of acute stroke. METHODS: We studied iron nasal exudate levels in 32 ischemic and 43 hemorrhagic stroke patients. All patients underwent neurological examination assessed by the National Institutes of Health Stroke Scale (NIHSS), brain computed tomography to the differential diagnosis of stroke subtype, laboratory tests, and measurement of iron levels in nasal exudate. RESULTS: The iron levels in nasal exudate were higher in hemorrhagic stroke patients. The area under the receiver operating characteristic curve for ischemic/hemorrhagic stroke discrimination was 0.896 (95% confidence interval 0.823-0.970) and cutoff point of 0.078 nmol/mg (sensitivity 93%, specificity 73%). CONCLUSIONS: Our findings suggest that iron levels in nasal exudate may be useful in the acute stage for the differential diagnosis between ischemic and hemorrhagic damage in acute stroke patients. They also open a potential field to study other biomarkers in nasal exudate in several neurological disorders. Clinical studies must be performed to confirm our results.

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

Background Differentiation 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. Methods We 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). Results A 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. Conclusions Non-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.

Vitamin K antagonist-associated intracerebral hemorrhage: lessons from a devastating disease in the dawn of the new oral anticoagulants.

BACKGROUND: Intracerebral hemorrhage (ICH) is the most feared complication associated with vitamin K antagonists (VKAs). We performed a retrospective study on the clinicoradiologic characteristics that influence its outcome. METHODS: We reviewed the clinical histories and neuroimaging studies of all patients attended at the Hospital Universitario Central de Asturias in 2010-2011 who had an ICH while being on VKA and analyzed the differential characteristics between patients with acceptable versus poor outcomes attending to 3 end points: death, poor outcome (modified Rankin Scale [mRS] score ≥ 4) at discharge, and poor outcome 3 months later. Additionally, CHA2DS2-VASc and HAS-BLED scores (validated tools for prediction of the risk of stroke and major hemorrhage, respectively, in patients with atrial fibrillation) were calculated to assess a priori risk-benefit balance for anticoagulant therapy. RESULTS: Eighty patients entered the sample (median age of 79 years). A priori annual risk of major bleeding surpassed ischemic stroke risk-without anticoagulation-only in 4. Fifty percent of the patients had an initial Glasgow Coma Scale (GCS) score lower than 13; in 51.3%, initial international normalized ratio was above their therapeutic range. Median hematoma size was 24.75 cc(3); relevant growth (≥33%) occurred in 29.4% of patients with a second computed tomography scan. On multivariable analysis, overall in-hospital mortality (47.5%) was related to prior antiplatelet therapy (P = .008), GCS (P = .001), and perilesional edema size (P = .036). Baseline mRS (P = .058) and National Institutes of Health Stroke Scale (NIHSS) scores (P = .008) were associated with poor outcome at discharge (77.5%). Initial NIHSS (P = .005) and glycemia (P = .038) predicted 3-month poor outcome (68.3%). VKA reversal was performed in almost all patients, which prevented assessment of its therapeutic value. CONCLUSIONS: VKA-associated ICH presents in a particularly vulnerable population and has a poor prognosis that may be reliably predicted by several clinicoradiologic features.

Incidence and mortality of cerebrovascular disease in Spain: 1,600,000 hospital admissions between 2001 and 2015.

BACKGROUND: To analyze the incidence and mortality of cerebrovascular diseases (CeVD) in Spain from 2001 to 2015. METHODS: Retrospective study of hospital incidence, hospital case fatality and population mortality, with records from the Spanish Government Statistics. Days of hospital stay and risk of death (RD) during admission were estimated adjusting for age, sex, first stroke (FS), atrial fibrillation (AF), diabetes, hypertension, and smoking. RESULTS: There were 1,662,487 stroke cases older than 15 years of age admitted to hospital (1,096,748 FS), with a national incidence = 291/105 in this period (Murcia maximum (367/105), Canary Islands minimum (238/105)). Population mortality (-50%) decreased while case fatality remained stable (-3%), despite the increase in the age of patients (+2.29 years) and the incidence (+25%). Canary Islands had the youngest patients (-3.5 years for men and -6 years for women) and the longest hospital stay (+5.1 days). Andalusia (odds ratio (OR) = 1.21 (1.19; 1.22)) and the Canaries (OR = 1.18 (1.15; 1.21)) had the highest RD. The factors associated to the highest increases in RD were FS (OR = 1.34 (95% confidence interval (CI) = 1.33-1.35)) and AF (OR = 1.30 (95% CI = 1.29-1.31)). CONCLUSION: Population mortality due to CeVD was reduced by half in Spain between 2001 and 2015, but hospital incidence increased. Andalusia and the Canary Islands had the highest RD in the country. These islands presented the lowest incidence, but their patients were younger, and their hospital stay longer. FS and AF were the factors associated with a higher RD.

Serum Prealbumin Levels on Admission as a Prognostic Marker in Stroke Patients Treated with Mechanical Thrombectomy.

INTRODUCTION: Prealbumin is a marker of malnutrition and inflammation. It has been associated with poor prognosis in cardiovascular disease, but less is known in stroke patients. Our objective was to evaluate the association of prealbumin levels at admission with prognosis in patients with stroke treated with mechanical thrombectomy. METHODS: Retrospective study of a prospective database of consecutive patients treated with mechanical thrombectomy. Clinical, radiological, and blood parameters including serum prealbumin, and prognostic variables such as respiratory infection, in-hospital mortality, and the modified Rankin scale at 3 months were collected. RESULTS: We included 319 patients between 2018 and 2019. Prealbumin levels were significantly lower in patients older than 80 years, women, patients with a prestroke Rankin score >2, a glomerular filtrate rate <60 mL/min, and in those with atrial fibrillation. Regarding prognostic variables, prealbumin levels were not associated with respiratory infection. Low prealbumin levels were associated with poor functional prognosis (Rankin score >2), in-hospital mortality, and 3-month mortality. In multivariate analysis, prealbumin was an independent risk factor associated with mortality at 3 months, OR 0.92 [0.86-0.98], p = 0.019. CONCLUSION: Lower prealbumin levels at admission behaved as an independent predictor of long-term mortality in patients treated with mechanical thrombectomy. These results should be replicated in other cohorts.

Efficacy and Safety of Endovascular Treatment in Acute Tandem Carotid Occlusions: Analysis of a Single-Center Cohort.

INTRODUCTION: Acute ischemic strokes with tandem occlusions, which represent 10-20% of all ischemic strokes, have a particularly poor prognosis. Since emergent treatment of tandem lesions has not been specifically addressed in randomized trials, there is an absence of standardized management. OBJECTIVE: We sought to assess the efficacy and safety of acute endovascular treatment in stroke due to tandem occlusions in our center and compare the results with previous reports. METHODS: From a prospective registry we analyzed data of 99 consecutive patients (males: 77.7%, mean age ± SD: 67.5 ± 9.5 years) with stroke due to tandem occlusions who underwent treatment with emergent carotid stenting and intracranial mechanical thrombectomy. Successful recanalization was defined as a TICI score of 2b-3 and a good functional outcome was defined as a modified Rankin scale score ≤2 at 90 days. Symptomatic intracranial hemorrhage (sICH) was considered when associated with worsening on the National Institutes of Health Stroke Scale (≥4 points). RESULTS: A successful recanalization rate was achieved in 87.8 and 48.5% of the patients had a good functional outcome. sICH and mortality rates were 12.1 and 20.2%, respectively, and 21.2% of the patients received combined treatment with intravenous thrombolysis, which did not affect neither the prognosis nor the recanalization or sICH rates. The time from symptom onset to recanalization and the degree of recanalization were the main factors associated with prognosis and the occurrence of sICH. CONCLUSIONS: Our results suggest that endovascular treatment with emergent carotid stenting and intracranial thrombectomy in patients with acute stroke due to tandem occlusions is an effective and safe procedure.

Endovascular reconstruction of internal carotid artery dissection in patients with acute ischemic stroke using the Wingspan stent.

OBJECTIVE: The purpose of this study is to demonstrate our experience in endovascular reconstruction of carotid dissections using the Wingspan Stent System™ (Boston Scientific, Natick, MA, USA), a device we use because of its high radial force and its navigation in extreme curves. METHODS: We treated 11 consecutive patients with acute ischemic stroke due to carotid dissection with the Wingspan stent, in the cervical carotid artery. RESULTS: Functional evaluation revealed that 10 of the 11 patients were independent at 3 months post surgery and that the 11 stents used were found to be patent at the 6-month follow-up digital subtraction angiography (DSA). CONCLUSIONS: The Wingspan stent is an alternative to classic carotid stents and flow diverters for the treatment of cervical internal carotid artery (ICA) dissection associated with ectasias or large loops. The device remains patent over the long term and it is not associated with arterial wall complications.

[Migraine as a vascular risk factor]. / La migraña como factor de riesgo vascular.

INTRODUCTION: Migraine and stroke are associated with a higher frequency than expected. Numerous studies have shown a significant, but controversial, association between migraine and vascular disease, not only in cerebral but also in other arterial beds. The full spectrum of this relationship includes coexisting stroke and migraine, stroke with clinical features of migraine and migraine-induced stroke. Why migraine is a risk factor and how it leads to stroke is not entirely understood, possibly because the mechanisms involved are multiple, complex and interrelated. AIM: Emphasizing the most recent papers, we review critically the current knowledge about the causal relationship between migraine and vascular disease and discuss its pathophysiology. DEVELOPMENT: Migraine is an independent risk factor for stroke, especially for young women with frequent migraine with aura attacks, who smoke and use oral contraceptives. Migraine has also been associated with lesions in the white matter and in other vascular territories. Potential pathogenic mechanisms include endothelium and vascular smooth muscle dysfunction, hypercoagulability, cortical spreading depression, genetic factors, patent foramen ovale, unfavourable vascular risk profile, arterial dissection and migraine-specific treatment. CONCLUSION: Considering that cerebrovascular disease is a major cause of disability and mortality and that migraine is a risk factor for vascular disease, understanding the relationship between migraine and vascular disease is necessary to reduce risks and optimize management and treatment.

[Endovascular treatment of carotid stenosis: an experience in the Hospital Universitario Central de Asturias]. / Tratamiento endovascular de la estenosis carotídea: experiencia en el Hospital Universitario Central de Asturias.

INTRODUCTION: Carotid stenosis accounts for about 25% of all ischaemic cerebrovascular events. Carotid angioplasty and stenting (CAS) is a minimally invasive procedure used as an alternative to carotid endarterectomy, especially in high surgical risk patients. AIM: To analyse the effectiveness and safety of the endovascular treatment of carotid stenosis in the Hospital Universitario Central de Asturias. PATIENTS AND METHODS: The study consisted in a retrospective analysis of the carotid stenoses treated by means of CAS between February 2005 and April 2010, and the following information was recorded: demographic data, clinical diagnosis, indication of treatment, time between the onset of symptoms and beginning of treatment, angiographic findings, complications and long-term follow-up (including the rate of restenosis). RESULTS: Altogether 121 patients were treated (77.8% males and 22.2% females), with a mean age of 70.8 ± 10.7 years. The main vascular risk factors were arterial hypertension (65.3%), smoking (61.2%) and dyslipidaemia (42.1%). In 86% of cases the stenoses were symptomatic and in the remaining 14% they were asymptomatic. In 60.3% of cases they were stenoses > 70%, in 30.6% they were preocclusive stenoses and in 9.1% they were recanalisations of unstable carotid occlusions. The mean treatment time was 17.0 ± 8.3 days after the ischaemic event. The residual stenosis was less than 30% in all cases. The morbidity and mortality rate at 30 days was 4.1% and the rate of restenosis throughout a mean follow-up of 31.2 ± 10.8 months was 2.4%. CONCLUSIONS: In our hospital CAS is considered an effective and safe technique, with a rate of complications that is within the parameters that justify its indication.