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Clinical and experimental observations prove that heparin-neutralizing doses of protamine increase pulmonary artery pressures and decrease systemic BP. Protamine also increases myocardial oxygen consumption, cardiac output, and heart rate, and decreases systemic vascular resistance. These cardiovascular effects have clinical consequences that have justified studies in this area. Protamine adverse reactions usually have three different categories: systemic hypotension, anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. The precise mechanism that explains protamine-mediated systemic hypotension is unknown. Four experimental protocols performed at Mayo Clinic, Rochester, MN, studied the intrinsic mechanism of protamine vasodilation. The first study reported in vitro systemic and coronary vasodilation after protamine infusion. The second in vitro study suggested that the pulmonary circulation is extensively involved in the protamine-mediated effects on endothelial function. The third study, carried out in anesthetized dogs, reported the methylene blue and nitric oxide synthase blockers neutralization of the protamine vasodilatatory effects. The fourth study suggested that protamine also causes endothelium-dependent vasodilation in heart microvessels and conductance arteries by different mechanisms including hyperpolarization. Reviewing these experimental results and our clinical experience, we suggest methylene blue as a novel approach to prevent and treat hemodynamic complications caused by the use of protamine after cardiopulmonary bypass. In the absence of prospective clinical trials, a growing body of cumulative clinical evidence suggests that methylene blue may be strongly considered as a therapeutic approach in the treatment of distributive shock. [ABSTRACT FROM AUTHOR]

We describe the case of a 40-year-old woman, affected by episodic cluster headache, who presented with a cluster headache triggered by exposure to high altitude. Her attacks were refractory to sumatriptan, very effective at sea level, but responded to oxygen. A pathophysiological mechanism is proposed. [ABSTRACT FROM AUTHOR]

The article focuses on a 43 year old patient suffering from trigeminal neuralgia (TN), Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and cluster headache. Both cluster headache and SUNCT are classified as trigeminal-autonomic cephalalgias (TACs). After an angio-MRI the patient was diagnosed with compression of the right trigeminal root with an arterial structure. Combination of gabapentin and amitriptyline was given for treatment.

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Background: Transcranial color Doppler (TCD) is currently the only noninvasive bedside tool capable of providing real-time information on cerebral hemodynamics. However, being operator dependent, TCD monitoring is not feasible in many institutions. Robotic assisted TCD (ra-TCD) was recently developed to overcome these constraints. The aim of this study was to evaluate the safety and feasibility of cerebral monitoring with a novel ra-TCD in acute neurovascular care., Methods: This is a two-center prospective study conducted between August 2021 and February 2022 at Padua University Hospital (Padua, Italy) and Kepler University Hospital (Linz, Austria). Adult patients with conditions impacting cerebral hemodynamics or patients undergoing invasive procedures affecting cerebral hemodynamics were recruited for prolonged monitoring (> 30 min) of the middle cerebral artery with a novel ra-TCD (NovaGuide Intelligent Ultrasound, NeuraSignal, Los Angeles, CA). Manual TCD was also performed for comparison by an experienced operator. Feasibility and safety rates were recorded., Results: A total of 92 patients (age: mean 68.5 years, range 36-91; sex: male 57 [62%]) were enrolled in the two centers: 54 in Padua, 38 in Linz. The examination was feasible in the majority of patients (85.9%); the head cradle design and its radiopacity hindered its use during carotid endarterectomy and mechanical thrombectomy. Regarding safety, only one patient (1.1%) reported a minor local edema due to prolonged probe pressure. Velocity values were similar between ra-TCD and manual TCD., Conclusions: This novel ra-TCD showed an excellent safety and feasibility and proved to be as reliable as manual TCD in detecting blood flow velocities. These findings support its wider use for cerebral hemodynamics monitoring in acute neurovascular care. However, further technical improvements are needed to expand the range of applicable settings., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Heart failure (HF) is the second most important cardiac risk factor for stroke after atrial fibrillation (AF). Few data are available on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with HF., Methods: The source of data is the multicentre Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). All AIS patients ≥ 18 years receiving MT were categorised in two groups: HF and no-HF. Baseline clinical and neuroradiological findings on admission were analysed., Results: Of 8924 patients, 642 (7.2%) had HF. Compared to the no-HF group, HF patients had higher prevalence of cardiovascular risk factors. Rate of complete recanalisation (TICI 2b-3) was 76.9% in HF vs 78.1% in no-HF group (p = 0.481). Rate of symptomatic intracerebral haemorrhage at 24-h non-contrast computed tomography (NCCT) was 7.6% in HF vs 8.3% in no-HF patients (p = 0.520). At 3 months, 36.4% of HF patients and 48.2% of no-HF patients (p < 0.001) had mRS 0-2, and mortality was, respectively, 30.7% and 18.5% (p < 0.001). In multivariate logistic regression, HF was independently associated with mortality at 3 months (OR 1.53, 1.24-1.88 95% CI, p < 0.001). In multivariate ordinal regression, HF patients had a probability of transitioning to a higher mRS level of 1.23 (1.05-1.44 95% CI, p = 0.012). The propensity score analysis of two groups matched for age, sex, and NIHSS at admission yielded the same results., Conclusion: MT is safe and effective in HF patients with AIS. Patients with HF and AIS suffered from higher 3-month mortality and unfavourable outcome regardless of acute treatments., (© 2023. Fondazione Società Italiana di Neurologia.)

Introduction: We describe a systemic neoplastic cryoglobulinemic vasculitis presenting as a large vessel occlusion (LVO) syndrome. We focus on a rare presentation of a rare condition., Case Report: A 68-year-old man was admitted to the Stroke Unit of Padova with a right middle cerebral artery syndrome. A cerebrovascular event was suspected and protocol for revascularization treatment was performed. Neuroimaging provided no evidence for infarcted tissue or medium-large vascular occlusion but hypothesized a vasculitic involvement of the small vessels of the right hemisphere. Further diagnostics demonstrated a microangiopathic involvement of the heart, kidneys, and lungs. Blood tests showed circulating cryoglobulins and further hematological investigation identified a chronic lymphatic leukemia-like lymphoproliferative disorder. High-dose steroid therapy improved the patient's clinical status and no neurological symptoms remained at discharge., Conclusion: We discuss the clinical-radiologic presentation of a small vessel vasculitis that mimics an LVO stroke. This case focuses on the relevance of concomitant multiorgan manifestations in the hyper-acute evaluation of LVO stroke, suggesting the clinical neurologist should consider alternative etiologies as these could provide important clinical implications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Stroke and cerebral vasculopathy are leading causes of morbidity and mortality in patients with sickle cell disease (SCD). Transcranial Doppler (TCD) is a reliable and validated predictor of stroke risk. Children with conditional or abnormal TCD are at an increased risk for stroke, which can be mitigated by red blood cell transfusion or hydroxyurea. Elucidating the relationship between cerebral hemodynamics and hemolytic anemia can help identify novel therapeutic approaches to reduce stroke risk and transfusion dependence., Methods: This long-term, real-world study was designed to evaluate the prevalence of TCD imaging (TCDi)-assessed flow velocities in children and to interrogate their relationship with markers of anemia and hemolysis., Results: In total, 155 children (median follow-up 79.8 months, 1358.44 patient-years) had 583 evaluable TCDi results. Only patients with HbSS or HbSβ 0 had abnormal (1.6%) or conditional (10.9%) TCDi. Children with abnormal or conditional TCDi had lower hemoglobin (Hb) and higher hemolysis markers. A linear correlation was detected between TCD velocity and Hb: an Hb increase of 1 g/dL corresponded to decreases in velocity in the internal carotid and middle cerebral arteries (6.137 cm/s and 7.243 cm/s). Moreover, patients with Hb >9 g/dL presented a lower risk of TCDi-associated events., Conclusion: These results support the need to optimize disease-modifying treatments that increase Hb and reduce hemolysis for stroke prevention in young children with SCD., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Cervical artery dissection (CeAD) causing a large vessel occlusion (LVO) stroke might represent a procedural challenge for mechanical thrombectomy (MT) impacting on its effects. The aim of the present study was to analyze safety, reperfusion rates, and clinical outcome of patients with CeAD treated by MT and compare these results with those obtained in non-CeAD patients., Methods: All consecutive LVO stroke patients undergoing MT between June 2015 and June 2021 at our University Stroke Center were analyzed. Baseline and procedural characteristics, recanalization rates, adverse events, and functional outcome of patients with CeAD were compared with non-CeAD patients., Results: MT was performed on 375 patients, 20 (5.3%) were diagnosed with CeAD. These patients were younger (52.9 ± 7.8 vs. 72.5 ± 12.9 years, P < 0.001), and showed lower rates of cardiovascular risk factors. In patients with CeAD, tandem occlusions were more frequent (65.0% vs. 14.4%, P < 0.001), groin to reperfusion time was longer (93.6 ± 34.9 vs. 68.3 ± 50.2 minutes, P = 0.01), and general anesthesia was more frequently utilized (70.0% vs. 27.9%, P < 0.001). Recanalization rates (Treatment in Cerebral Infarction 2b-3: 100.0% vs. 88.5%) and MT-related adverse events (10.0% vs. 10.7%) did not differ between the groups, while functional outcome was better in patients with CeAD (modified Rankin Scale 0-2 at 3 months: 85.0% vs. 62.0%, P = 0.038)., Conclusions: Although CeAD represents a procedural challenge, MT constitutes a safe and effective treatment for patients with CeAD with LVO stroke., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Subclinical atrial fibrillation (SCAF) may represent a cause of embolic stroke of undetermined source (ESUS) and its detection has important implications for secondary prevention with anticoagulation. Indications to implantable cardiac monitors (ICM) include SCAF detection. The aims of this study were to (1) evaluate the frequency of ICM-detected SCAF; (2) determine predictors of SCAF; and (3) identify patients who would benefit most from ICM implantation., Methods: Between February 2017 and November 2020, all consecutive patients referred for ICM implantation after a diagnosis of ESUS and without previous history of atrial fibrillation or atrial flutter were included in this study. SCAF was diagnosed if the ICM electrogram demonstrated an episode of irregularly irregular rhythm without distinct P waves lasting > 2 min., Results: We enrolled 109 patients (age 66, SD = 13 years; 36% females). During a median follow-up of 19.2 (IQR 11.0-27.5) months, SCAF episodes were detected in 36 (33%) patients. Only abnormal P wave terminal force in lead V1, left atrial end-systolic indexed volume > 34 ml/m 2 , and BMI > 25 kg/m 2 were independently associated with an increased risk of SCAF (HR 2.44, 95% CI 1.14-5.21, p = 0.021; HR 2.39, 95% CI 1.11-5.13, p = 0.026; and HR 2.64, 95% CI 1.06-6.49, p = 0.036 respectively). The ROC curve showed that the presence of all three parameters had the best accuracy (74%) to predict SCAF detection (sensitivity 39%, specificity 91%)., Conclusion: A multiparametric evaluation has the best accuracy to predict SCAF in ESUS patients and may help identifying those who would benefit most from ICM., (© 2022. Fondazione Società Italiana di Neurologia.)

Background: Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke with a huge impact on patients and families. Expanded use of oral anticoagulants and ageing population might contribute to an epidemiological change. In view of these trends, we planned a study to obtain a contemporary picture and identify early prognostic factors to improve secondary prevention., Methods: This multicenter prospective cohort study included consecutive adult patients with non-traumatic ICH admitted to three academic Italian hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Demographic characteristics, vascular risk profile, clinical data and main radiological characteristics were correlated to 90-day clinical outcome., Results: Out of 682 patients [mean age: 73 ± 14 years; 316 (46.3%) females] enrolled in this study, 40% died [86/180 (47.8%) in Salerno, 120/320 (37.5%) in Padova, 67/182 (36.8%) in Reggio Emilia; p < 0.05)] and 36% were severely disabled at 90 days. Several factors were associated with a higher risk of poor functional outcome such as antithrombotic drug use, hyperglycemia, previous cerebrovascular accident, low platelet count, and pontine/massive/intraventricular hemorrhage. However, at multivariate analysis only pre-ICH mRS score (OR 30.84), GCS score at presentation (OR 11.88), initial hematoma volume (OR 29.71), and NIHSS score at presentation (OR 25.89) were independent predictors of death and poor functional outcome., Conclusion: Despite the heterogeneity among centers, this study on ICH has identified four simple prognostic factors that can independently predict patients outcome, stratify their risk, and guide their management., (© 2023. The Author(s).)

Background: The aim of this study was to investigate the prognostic role of hematoma characteristics and hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH)., Methods: This multicenter prospective cohort study enrolled consecutive adult patients with non-traumatic ICH admitted to three Italian academic hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Early noncontrast CT (NCCT) features of the hematoma, including markers of HE, and 3-month outcome were recorded. Multivariable logistic regression analysis was performed to identify predictors of poor outcome., Results: A total of 682 patients were included in the study [mean age: 73 ± 14 years; 316 (46.3%) females]. Pontine and massive hemorrhage, intraventricular bleeding, baseline hematoma volume > 15 mL, blend sign, swirl sign, margin irregularity ≥ 4, density heterogeneity ≥ 3, hypodensity ≥ 1, island sign, satellite sign, and black hole sign were associated with a higher risk of mortality and disability. However, at multivariate analysis only initial hematoma volume (OR 29.71) proved to be an independent predictor of poor functional outcome at 3 months., Conclusion: Simple hematoma volume measured on baseline CT best identifies patients with a worse outcome, while early NCCT markers of HE do not seem to add any clinically significant information., (© 2022. The Author(s).)

Background and Purpose: No current consensus exists on the best anesthetic management of ischemic stroke patients undergoing mechanical thrombectomy. Both conscious sedation (CS) and general anesthesia (GA) are currently considered valid anesthetic strategies, yet patients managed under CS may require emergent conversion to GA, which has been associated with worse outcomes. The aim of this study was to analyze the conversion rate and potential risk factors for GA conversion during mechanical thrombectomy., Methods: Two-hundred and twenty-seven patients with consecutive acute anterior circulation ischemic stroke treated with mechanical thrombectomy and initiated under CS or local anesthesia were included in this retrospective analysis. Conversion rate to GA was calculated, while univariate and multivariate analysis were used to identify risk factors., Results: Twenty patients (8.8%) were switched to GA. Multivariate analysis identified procedure duration (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.00-1.02, p value 0.028), tandem stroke (OR 8.57, 95% CI 2.06-35.7, p value 0.003), Sequential Organ Failure Assessment (SOFA) (OR 1.76, 95% CI 1.19-2.61, p value 0.005), and number of pharmacological agents used (OR 5.76, 95% CI 2.49-13.3, p value <0.001) as independently associated with conversion to GA., Conclusion: In our study, tandem occlusion, longer endovascular procedures, SOFA, and number of pharmacological agents used predicted the risk of emergent conversion to GA in stroke patients undergoing endovascular treatment. Prospective studies investigating optimal CS strategies are deemed necessary., (© 2021 S. Karger AG, Basel.)