Palladium nanoclusters as a label to determine GFAP in human serum from donors with stroke by bimodal detection: inductively coupled plasma-mass spectrometry and linear sweep voltammetry.

Water-soluble, stable, and monodisperse palladium nanoclusters (PdNCs) were synthesized using NaBH4 as a reductant and lipoic acid as a ligand. PdNCs, measured by high-resolution transmission electron microscopy, showed a round shape and a diameter of 2.49 ± 0.02 nm. It was found that each PdNC contains 550 Pd atoms on average. These PdNCs offer high amplification as a label of biochemical reactions when inductively coupled plasma-mass spectrometry (ICP-MS) is used as a detector. In addition, PdNCs have catalytic activity on electrochemical reactions, allowing detection by linear sweep voltammetry (LSV). As a proof of applicability, a competitive immunoassay based on PdNC labels was developed for the determination of glial fibrillary acidic protein (GFAP) in human serum, comparing ICP-MS and LSV detection. GFAP is a biomarker for differentiating between patients with ischemic stroke (IS) and hemorrhagic stroke (HS). The limit of detection (LoD), corresponding to IC10 (4-parameter logistic curve), was 0.03 pM of GFAP, both by ICP-MS and LSV, being lower than the 0.31 pM LoD provided by the ELISA commercial kit. Using the error profile method, 0.03 pM and 0.11 pM LoDs were obtained respectively by ICP-MS and LSV: LoD is lower by ICP-MS due to the better precision of the measurements. The analyses of human serum samples from IS, HS, and control (CT) donors using PdNC labels and detection by ICP-MS and LSV were validated with a commercial ELISA kit (for CT donors only ICP-MS provided enough sensitivity). Results point out toward the future use of PdNCs as a label in other immunoprobes for the determination of specific proteins requiring very low LoDs as well as the development of electrochemical decentralized methodologies.

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.

Craniocervical Junction Calcium Pyrophosphate Deposition Causing Hypoglossal Nerve Palsy.

This case report describes an 80-year-old patient's right-sided hemicranial headache, right-sided tongue hemiatrophy with fasciculations and deviation, right side of the tongue on protrusion, and mild dysarthria.

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.

Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke.

Background and Purpose: We aimed to determine the prevalence and predictors of delayed neurological improvement (DNI) after complete endovascular reperfusion in anterior circulation acute ischemic stroke (AIS). Methods: Retrospective analysis of an online multicenter prospective reperfusion registry of patients with consecutive anterior circulation AIS treated with endovascular thrombectomy (EVT) from January 2018 to June 2019 in tertiary stroke centers of the NORDICTUS (NORD-Spain Network for Research and Innovation in ICTUS) network. We included patients with AIS with a proximal occlusion in whom a modified Thrombolysis in Cerebral Infarction 3 reperfusion pattern was obtained. DNI was defined if, despite absence of early neurological improvement during the first 24 hours, patients achieved functional independence on day 90. Clinical and radiological variables obtained before EVT were analyzed as potential predictors of DNI. Results: Of 1565 patients with consecutive AIS treated with EVT, 1381 had proximal anterior circulation occlusions, 803 (58%) of whom achieved a modified Thrombolysis in Cerebral Infarction 3. Of these, 628 patients fulfilled all selection criteria and were included in the study. Mean age was 73.8 years, 323 (51.4%) were female, and median baseline National Institutes of Health Stroke Scale was 16. Absence of early neurological improvement was observed in 142 (22.6%) patients; 32 of these (22.5%) achieved good long-term outcome and constitute the DNI group. Predictors of DNI in multivariable-adjusted logistic regression were male sex (odds ratio, 6.4 [95% CI, 2.1­22.3] P=0.002), lower pre-EVT National Institutes of Health Stroke Scale score (odds ratio, 1.4 [95% CI, 1.2­1.5], P<0.001), and intravenous thrombolysis (odds ratio, 9.1 [95% CI, 2.7­30.90], P<0.001). Conclusions: One-quarter of patients with anterior circulation AIS who do not clinically improve within the first 24 hours after complete cerebral endovascular recanalization will achieve long-term functional independence, regardless of the poor early clinical course. Male sex, lower initial clinical severity, and use of intravenous thrombolysis before EVT predicted this clinical pattern.

Trigeminal neuralgia as the sole neurological manifestation of COVID-19: A case report.

OBJECTIVE: To describe a case report of trigeminal neuralgia (TN) due to coronavirus disease-2019 (COVID-19). BACKGROUND: In March 2020, the World Health Organization declared COVID-19 as a pandemic. Respiratory system manifestations are dominant in this new disease. However, numerous case series and reviews have been published on the neurological manifestations, highlighting the potential neurotropism of the new coronavirus. METHODS: We describe a clinical case of TN during COVID-19 and we discuss the differential diagnosis and the potential pathogenic mechanism according to the literature. RESULTS: A 65-year-old man with general malaise and typical respiratory symptoms of COVID-19, who presented with paroxysmal lancinating pain in the right V1 trigeminal territory without other neurological symptoms. General blood test and neuroimaging study were normal. A rapid test showed positive IgG and IgM serologies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The patient was diagnosed with TN secondary to a viral infection by SARS-CoV-2. Facial pain resolved with the improvement of COVID-19. CONCLUSIONS: The new coronavirus SARS-CoV-2 is a possible etiology of secondary TN. Nevertheless, more studies are needed to elucidate the neuropathology of this viral infection.

Impact of Mediterranean Diet prior to Stroke on the Prognosis of Patients Undergoing Endovascular Treatment.

INTRODUCTION: Mediterranean diet (MeDiet) has been associated with lower risk of stroke. Additionally, animal models suggested that some components of MeDiet are associated with better outcomes after ischemic stroke (IS). We aimed to evaluate the association between global adherence to the MeDiet and the consumption of particular components of the MeDiet with stroke outcomes. MATERIAL AND METHODS: Multicenter observational study of consecutive IS patients treated with endovascular therapy. Inclusion criteria were large anterior circulation vessel occlusion and pre-stroke modified Rankin scale (mRS) <2. Adherence to MeDiet prior to stroke was evaluated using MEDAS 14-item scale. We evaluated the total score and also individual components of the scale. Clinical, radiological, and prognostic variables were collected. Good functional prognosis was considered as mRS ≤2 and complete recanalization as thrombolysis in cerebral infarction 3. RESULTS: From January 1 to October 30, 2018, 239 patients were included (mean age 71 years, 48% women, median baseline NIHSS 16). Median MEDAS scale was 8 points (7-10). Patients with a higher adherence to MeDiet had significantly lower total and LDL-cholesterol levels. Total adherence score was not associated with stroke outcomes. In multivariate analyses, consumption of olive oil as the principal source of fat was independently associated with good functional outcome at 3 months, OR 3.2 (1.1-10.1) and daily consumption of wine was independently associated with complete recanalization, OR 2.0 (1.1-3.8). CONCLUSIONS: Our study suggests that some components of MeDiet, such as olive oil and wine consumption, are related to better prognosis after stroke. More studies are needed to confirm these findings.

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.

Exercise and Stroke.

Stroke is a leading cause of mortality and morbidity all around the world. Identification of stroke risk factors and protective lifestyles is necessary for optimizing personalized treatment and reducing mortality. Sedentary lifestyle is a well-known modifiable risk factor in primary and secondary stroke prevention. Also, in recent years, exercise has been described as a neuroprotective and neuroreparative factor. Here we summarized the existing available evidence of the relationship between physical activity and stroke.

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.

Sudden hemichorea and frontal lobe syndrome: a rare presentation of unbalanced polycythaemia vera.

Polycythaemia vera (PV) is an haematological neoplasm that frequently presents neurological symptoms. However, chorea is a rare complication of this disease, occurring in less than 5% of the patients. Cognitive impairment related to PV unbalanced is also a rare complication, and it can improve with proper treatment. We present a 96-year-old-man with acute-onset hemichorea and frontal lobe syndrome with no vascular pathology in the basal ganglia or frontal region. A clear relationship was observed between the onset of involuntary movements and the cognitive impairment and worsening of haematological parameters in the patient. After causal and symptomatic treatment, the patient's clinical status improved. In the elderly, PV must be considered as a cause of acute chorea and sudden cognitive impairment, as early diagnosis leads to effective treatment and prevention of complications.

Comorbidity between idiopathic overactive bladder and chronic migraine.

Objective We tested whether overactive bladder (OAB) and chronic migraine (CM) could be comorbid. Patients and methods CM women, aged 40-69 years, answered a validated OAB questionnaire. Prevalence data were compared with those reported in our country in the general population (GP) using the same questionnaire. Results We interviewed 231 CM women. Eighty-four met OAB criteria. OAB prevalence in CM patients was significantly higher than that found in the GP (36.4% vs. 21.8% in the GP; p = 0.0001). There were 34 CM women aged 40-49 years (34.3% vs. 15.2%; p = 0.001), 35 aged 50-59 years (38.9% vs. 21.7%; p = 0.004) and 15 aged 60-69 years (35.7% vs. 24.5%; p = 0.15) meeting OAB criteria. Seventy-seven (33% vs. 9.9%; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1%, p = 0.002) experienced nocturia and 43 (18.6% vs. 8.1%; p = 0.001) urinary incontinence. Conclusion In this exploratory study, at least in women, OAB and CM are comorbid, which suggests shared mechanisms.

Sudden paraplegia after lumbar puncture as a clue in the diagnosis of a patient with spinal dural arteriovenous fistula.

PURPOSE: Spinal dural arteriovenous fistula (SDAVF) is manifested as congestive myelopathy with progressive motor, sensory and urinary symptoms. Sometimes, clinical picture and magnetic resonance imaging of the spinal cord are not specific and the diagnosis becomes troublesome. METHODS: We present a 68-year-old male with a progressive paraparesis of unknown etiology over the course of 12 months. Immediately after LP, the patient remarked a sudden worsening in muscular balance of his inferior limbs and a worsening of urinary retention. This fact was the clue to the SDAVF diagnosis. RESULTS: SDAVF was totally resolved after surgical treatment. During next months, paraplegia slightly improved and he is currently receiving rehabilitation treatment. CONCLUSIONS: Acute paraplegia or sudden worsening of previous symptoms secondary to decreasing in cerebrospinal fluid pressure after lumbar puncture has been described, so physicians should be aware of this dramatic and avoidable complication.

Descripción de una serie hospitalaria de pacientes con fístula espinal / Description of a series of hospital patients with a spinal fistula

Introducción. Aunque las fístulas espinales suponen el 70% de las malformaciones arteriovenosas espinales, son una entidad infradiagnosticada. El shunt arteriovenoso produce una congestión vascular que da lugar a una mielopatía progresiva, en ocasiones irreversible si no se trata de forma precoz. Objetivo. Describir las características clinicorradiológicas de una serie de pacientes con fístula espinal. Pacientes y métodos. Se realizó una búsqueda retrospectiva de pacientes con diagnóstico de fístula espinal ingresados en el área de neurociencias de un hospital de tercer nivel asistencial. Resultados. Se identificaron 19 pacientes (7 mujeres y 12 varones) con una edad media de 56 años. La fístula espinal fue de tipo I en un 79% de los pacientes y la localización dorsal fue la más frecuente. La mayoría de los casos presentó un curso progresivo (90%). Un 74% de los pacientes se diagnosticó mediante resonancia magnética. En cuatro casos fue necesaria la realización de una angiografía para llegar al diagnóstico, y en uno de ellos se precisó una biopsia intraoperatoria. Se realizaron tres punciones lumbares, en dos de las cuales se objetivó pleocitosis linfocitaria e hiperproteinorraquia. El retraso diagnóstico medio fue de nueve meses. Se trató a un 79% de los pacientes, y de ellos sólo mejoró el 10%. Conclusiones. Ante una clínica sugestiva de fístula espinal, debe realizarse una angiografía espinal diagnóstica aunque el paciente estudiado pueda presentar características licuorales atípicas y normalidad en la resonancia magnética medular (AU)

Introduction. Although spinal fistulas account for 70% of all spinal arteriovenous malformations, they are an underdiagnosed condition. The arteriovenous shunt produces vascular congestion that gives rise to a progressive myelopathy, sometimes irreversible if it is not treated in the early stages. Aim. To describe the clinicoradiological characteristics of a series of patients with spinal fistulas. Patients and methods. A retrospective search was conducted for patients diagnosed with a spinal fistula who were hospitalised in the neuroscience area of a tertiary care hospital. Results. A total of 19 patients (7 females and 12 males) were identified, with a mean age of 56 years. The spinal fistula was type I in 79% of patients, and a dorsal location was the most frequent. Most of the cases (90%) presented a progressive course. Magnetic resonance imaging was used in the diagnosis in 74% of the patients. In four cases angiography was required to reach a diagnosis, and in one of them it was necessary to perform an intraoperative biopsy. Three lumbar punctures were performed, two of which revealed lymphocytic pleocytosis and high protein levels in cerebrospinal fluid. The average diagnostic delay was nine months. Seventy-nine per cent of the patients were treated and only 10% of them improved. Conclusions. When faced with a clinical picture suggestive of a spinal fistula, a diagnostic spinal angiography must be carried out, although the patient under study may present atypical cerebrospinal fluid characteristics and normal results in magnetic resonance imaging of the spinal cord (AU)

Ojo con los colirios oftálmicos en pacientes con accidente isquémico transitorio / Keep an eye on transient ischaemic attacks in patients treated with eyedrops

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No Change in Interictal PACAP Levels in Peripheral Blood in Women With Chronic Migraine.

OBJECTIVE: To determine total pituitary adenylate cyclase activating polypeptide (PACAP) in peripheral blood as a potential marker of the activation of the parasympathetic arm of the trigemino-vascular system in chronic migraine (CM) in a case-control study. METHODS: Women older than 17 and diagnosed as CM were recruited. Healthy women with no headache history and women with episodic migraine (EM) served as control groups. Total PACAP and vasoactive intestinal peptide (VIP) levels were determined in blood samples obtained from the right antecubital vein by ELISA outside a migraine attack and having taken no symptomatic medication the day before. RESULTS: We assessed serum samples from 86 women with CM, 32 healthy women, and 35 women with EM. There were no differences in PACAP levels in CM patients (109.8 ± 43.8, 97.4 [32.5-253.1] pg/mL), controls (108.7 ± 43.0, 98.7 [50.7-197.3] pg/mL), or EM patients (98.8 ± 34.3, 94.2 [52.0-190.7] pg/mL). VIP levels were significantly increased (P = .027) in CM as compared to control healthy women (136.0 ± 111.5 pg/mL; 103.1 [20.5-534.0] pg/mL vs 88.6 ± 61.0 pg/mL; 66.0 [21.1-256.1]) and EM patients (103.0 ± 56.7 pg/mL; 103.5 [15.2-263.0] pg/mL). In the range of this study variables such as age, CM duration, the presence of aura, analgesic overuse, depression, fibromyalgia, vascular risk factors, history of triptan consumption or kind of preventative treatment did not significantly influence PACAP or VIP levels. CONCLUSION: In contrast to VIP, interictal PACAP level measured in peripheral blood does not seem to be a biomarker reflecting parasympathetic activation in CM.

Safety and Efficacy of Mechanical Thrombectomy in Acute Ischemic Stroke of Anticoagulated Patients-A Prospective Observational Study.

BACKGROUND: Anticoagulated patients (APs) are excluded from the acute stroke management with alteplase in Europe, not in the United States. They could benefit from mechanical thrombectomy (MT), which was not undoubtedly proven. There are scarce data about its results in such patients. The authors' aim is to analyze the efficacy and safety of MT in APs presenting with an acute stroke in our institution. METHODS: Prospective observational study comparing 30 APs and 109 non-anticoagulated patients (N-APs) underwent direct MT without alteplase. Demographic data, clinical severity (National Institutes of Health Stroke Scale [NIHSS]), efficacy (recanalization thrombolysis in cerebral infarction [TICI] ≥ 2b and modified Rankin Scale score ≤ 2 at 3 months), and security (symptomatic intracranial hemorrhage [SICH], mortality at 3 months) were compared between both groups. RESULTS: In both groups men were more frequent (63.3% of APs were men and 61.5% of N-APs were men). Mean age was 73 in APs and 67.2 in N-APs. Median NIHSS was similar (17 APs; 16 N-APs), also TICI greater than or equal to 2b (93.3% APs; 89.9% N-APs). The 3-month modified Rankin Scale score less than or equal to 2 was 46.7% in APs and 55.2% in N-APs (P = .40). SICH was present in 16.7% of APs and 8.3% of N-APs (P = .15). Mortality at 3 months was 6.7% in APs and 19% in N-APs (P = .08). CONCLUSIONS: MT is a valid treatment option in APs. It achieves an efficacy as in N-APs with a tendency to suffer more from SICH, but lower mortality. We hypothesize that cardioembolic clots may be easier to be removed than atherotrombotics, and that embolic stroke in APs might be less severe than that in N-APs or might suffer less of other complications than atherotrombotics.