Role of Advanced Hemodynamic Ultrasound Evaluation in the Differential Diagnosis of Middle Cerebral Artery Stenosis: Introducing Morphological Criteria.

OBJECTIVE: The aim of the work described here was to determine the possible impact of the new technique advanced hemodynamic ultrasound evaluation (AHUSE) in identification of severe intracranial stenosis. Transcranial Doppler (TCD) and transcranial color-coded Doppler (TCCD) provide reliable velocimetric data, the indirect analysis of which allows us to obtain information on the patency of vessels and assumed stenosis range. However, very tight stenoses (>95%) cannot be detected with velocimetric criteria because of spectrum drops and the absence of high velocities, so that the right curve of the Spencer equation cannot be solved. Likewise, high velocities are not detected when analyzing morphologically long stenosis. Furthermore, the current classifications based on velocimetric criteria do not provide any categorization on stenoses with multiple acceleration points (MAPs). METHODS: With this Technical Note we aim to introduce, in addition to velocimetric criteria, more morphological criteria based on TCCD with the algorithm of AHUSE to optimize the characterization of intracranial stenosis (IS). TCCD-AHUSE relies on intensity-based next-generation techniques and can be used to identify IS with MAPs and simultaneously perform a morphological assessment of the stenosis length. RESULTS: We introduce a new technical ultrasound (U) approach that we tested in a sample of four different types of stenoses combining velocimetric data and AHUSE using Esaote Microvascularization (MicroV) technique to the M1 tract of the middle cerebral artery (MCA). CONCLUSION: The authors believe that a multiparametric evaluation is more sensitive and supports the clinician by introducing the morphological concept, not just the velocimetric concept, to differentiate the IS pattern of MCA. The potential for developing a diagnostic/prognostic algorithm is discussed.

Transcranial Doppler Ultrasonography in Pre-hospital Management of Stroke: Can it make a Difference?

The aim of this paper is to discuss the use of transcranial doppler in the pre-hospital management of stroke. In the pre-hospital organization, neurological defect scales are used, but they are often indicative of the occlusions of anterior circulation and not of the posterior circulation. Patients with posterior circulation stroke are sometimes not diagnosed and clinically treated. In the pre-hospital phase, the transcranial doppler may identify an occlusion of the large cerebral vessels and be useful for stroke patients, in particular those with posterior occlusions, for a more precise diagnosis and consequently for adequate treatment in the excellence centers for stroke.

Ultrasound Diagnostic Method in Vascular Dementia: Current Concepts.

BACKGROUND: Increasing interest in identifying cerebral hemodynamics alterations as a cause of possible onset or worsening of cognitive impairment in elderly patients with vascular risk factors. INTRODUCTION: Intracranial ultrasound is a non-invasive, repeatable inexpensive method for recording variation of the cerebral vascular tree in physiological and pathological conditions and the diagnosis of vascular dementia (VaD). METHODS: PubMed, Embase, Cochrane library and reference lists have been searched for articles published until March 30, 2020. RESULTS: Clinical studies reported different Transcranial Doppler (TCD) parameters and subsequently transcranial duplex with color code (TCCD) in patients affected by vascular dementia. The number of studies using TCCD remains limited and most of the available data are still based on TCD. However, the use of transcranial Doppler could better stratify elderly patients with initial signs of cognitive impairment. CONCLUSION: Intracranial ultrasound employment to detect cerebral hemodynamic changes in VaD patients has been briefly discussed in this review.

Rivaroxaban in cervical and "cervico-cerebral" artery dissections: a new therapeutic option?

Antiplatelet agents and vitamin K antagonists (VKA) are usually used in the treatment of cervical (carotid or vertebral) artery dissections (CADs); however, data about the use of direct oral anticoagulants (DOACs) in these conditions are very limited. DOACs have proven to be effective in stroke reduction in non-valvular atrial fibrillation and, when possible, they are preferred to warfarin because of their better safety profile. We describe four cases of CADs and, firstly in literature, cervico-cerebral (CCADs) in young patients (average age of 42 years) treated with rivaroxaban 20 mg daily. Three of these four dissections had affected the vertebral artery (condition with an unfavorable prognosis and more often complicated by subarachnoid hemorrhages), and the other one was a carotid dissection at the extra-intracranial passage. All patients were followed clinically and with serial neurosonological examinations at 1, 3, and 6 months and with magnetic resonance angiography (MRA) at 6 months. All patients presented a good outcome with vascular recanalization without stroke recurrence or bleedings, even in patients with intracranial vertebral artery involvement. DOACs could be an alternative in young patients with CADs and their use could be considered in intracranial artery dissections too.

The predictive power of transcranial sonography in movement disorders: a longitudinal cohort study.

Transcranial sonography (TCS) is a noninvasive, easily performed, and commonly available neuroimaging technique useful for the study of brain parenchyma in movement disorders. This tool has been increasingly used in the diagnosis of Parkinson's disease and atypical parkinsonism. The aim of the study was to evaluate the applicability of this technique as supportive tool in the early diagnosis of movement disorders. We performed TCS on 315 individuals which were diagnosed as healthy controls or affected by idiopathic Parkinson's disease, monogenetic subtypes of Parkinson's disease, atypical parkinsonism, and Dementia with Lewy bodies. Five TCS diagnostic patterns were defined on the basis of substantia nigra's and lenticular nuclei's echogenicity. TCS evaluations were performed by two blinded neuro-sonographers. Clinical diagnosis on all individuals was performed at baseline and at 4-year follow-up. The concordance rate between TCS patterns and clinical diagnosis and the specificity of TCS pattern to discriminate each group of individuals were compared at baseline and at follow-up. The concordance rate between TCS patterns and clinical diagnosis of all individuals was 84% at baseline and increased at follow-up (91%) significantly (p = 0.01). The specificity of TCS pattern in the comparison between patients diagnosed as affected by idiopathic Parkinson's disease and atypical parkinsonism showed a significant increase at follow-up (p = 0.03). Our study strongly confirms the role of TCS as a noninvasive and cost-effective tool in early diagnosis of movement disorders.

MicroV Technology to Improve Transcranial Color Coded Doppler Examinations.

The purpose of this review is to provide an update on technology related to Transcranial Color Coded Doppler Examinations. Microvascularization (MicroV) is an emerging Power Doppler technology which can allow visualization of low and weak blood flows even at high depths, thus providing a suitable technique for transcranial ultrasound analysis. With MicroV, reconstruction of the vessel shape can be improved, without any overestimation. Furthermore, by analyzing the Doppler signal, MicroV allows a global image of the Circle of Willis. Transcranial Doppler was originally developed for the velocimetric analysis of intracranial vessels, in particular to detect stenoses and the assessment of collateral circulation. Doppler velocimetric analysis was then compared to other neuroimaging techniques, thus providing a cut-off threshold. Transcranial Color Coded Doppler sonography allowed the characterization of vessel morphology. In both Color Doppler and Power Doppler, the signal overestimated the shape of the intracranial vessels, mostly in the presence of thin vessels and high depths of study. In further neurosonology technology development efforts, attempts have been made to address morphology issues and overcome technical limitations. The use of contrast agents has helped in this regard by introducing harmonics and subtraction software, which allowed better morphological studies of vessels, due to their increased signal-to-noise ratio. Having no limitations in the learning curve, in time and contrast agent techniques, and due to its high signal-to-noise ratio, MicroV has shown great potential to obtain the best morphological definition.

Anticoagulants Resumption after Warfarin-Related Intracerebral Haemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy).

Whether to resume antithrombotic treatment after oral anticoagulant-related intracerebral haemorrhage (OAC-ICH) is debatable. In this study, we aimed at investigating long-term outcome associated with OAC resumption after warfarin-related ICH, in comparison with secondary prevention strategies with platelet inhibitors or antithrombotic discontinuation. Participants were patients who sustained an incident ICH during warfarin treatment (2002-2014) included in the Multicenter Study on Cerebral Hemorrhage in Italy. Primary end-point was a composite of ischemic stroke/systemic embolism (SE) and all-cause mortality. Secondary end-points were ischemic stroke/SE, all-cause mortality and major recurrent bleeding. We computed individual propensity score (PS) as the probability that a patient resumes OACs or other agents given his pre-treatment variables, and performed Cox multivariable analysis using Inverse Probability of Treatment Weighting (IPTW) procedure. A total of 244 patients qualified for the analysis. Unlike antiplatelet agents, OAC resumption was associated with a lower rate of the primary end-point (weighted hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09-0.45), as well as of overall mortality (weighted HR, 0.17; 95% CI, 0.06-0.45) and ischemic stroke/SE (weighted HR, 0.19; 95% CI, 0.06-0.60) with no significant increase of major bleeding in comparison with patients receiving no antithrombotics. In the subgroup of patients with atrial fibrillation, OACs resumption was also associated with a reduction of the primary end-point (weighted HR, 0.22; 95% CI, 0.09-0.54), and the secondary end-point ischemic stroke/SE (weighted HR, 0.09; 95% CI, 0.02-0.40). In conclusion, in patients who have an ICH while receiving warfarin, resuming anticoagulation results in a favorable trade-off between bleeding susceptibility and thromboembolic risk.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial).

BACKGROUND AND PURPOSE: Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. METHODS: According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. RESULTS: We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60-1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). CONCLUSIONS: Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Development of an education campaign to reduce delays in pre-hospital response to stroke.

BACKGROUND: Systematic reviews call for well-designed trials with clearly described intervention components to support the effectiveness of educational campaigns to reduce patient delay in stroke presentation. We herein describe the systematic development process of a campaign aimed to increase stroke awareness and preparedness. METHODS: Campaign development followed Intervention Mapping (IM), a theory- and evidence-based tool, and was articulated in two phases: needs assessment and intervention development. In phase 1, two cross-sectional surveys were performed, one aiming to measure stroke awareness in the target population and the other to analyze the behavioral determinants of prehospital delay. In phase 2, a matrix of proximal program objectives was developed, theory-based intervention methods and practical strategies were selected and program components and materials produced. RESULTS: In phase 1, the survey on 202 citizens highlighted underestimation of symptom severity, as in only 44% of stroke situations respondents would choose to call the emergency service (EMS). In the survey on 393 consecutive patients, 55% presented over 2 hours after symptom onset; major determinants were deciding to call the general practitioner first and the reaction of the first person the patient called. In phase 2, adult individuals were identified as the target of the intervention, both as potential "patients" and witnesses of stroke. The low educational level found in the patient survey called for a narrative approach in cartoon form. The family setting was chosen for the message because 42% of patients who presented within 2 hours had been advised by a family member to call EMS. To act on people's tendency to view stroke as an untreatable disease, it was decided to avoid fear-arousal appeals and use a positive message providing instructions and hope. Focus groups were used to test educational products and identify the most suitable sites for message dissemination. CONCLUSIONS: The IM approach allowed to develop a stroke campaign integrating theories, scientific evidence and information collected from the target population, and enabled to provide clear explanations for the reasons behind key decisions during the intervention development process. TRIAL REGISTRATION: NCT01881152 . Retrospectively registered June 7 2013.

The National Institutes of Health Stroke Scale: Its Role in Patients with Posterior Circulation Stroke.

The National Institutes of Health Stroke Scale (NIHSS) is indispensable for both prognosis and treatment in patients with acute ischemic stroke. However, there is subtype of acute ischemic stroke (i.e., posterior circulation stroke) that is difficult to diagnose using the NIHSS. The authors report the limits of NIHSS in this stroke subtype, suggesting thereby the need to modify and render it more appropriate for the evaluation of the neurological signs occurring in posterior circulation stroke.

Serum cholesterol levels, HMG-CoA reductase inhibitors and the risk of intracerebral haemorrhage. The Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy).

OBJECTIVE: Although a concern exists that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) might increase the risk of intracerebral haemorrhage (ICH), the contribution of these agents to the relationship between serum cholesterol and disease occurrence has been poorly investigated. METHODS: We compared consecutive patients having ICH with age and sex-matched stroke-free control subjects in a case-control analysis, as part of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy), and tested the presence of interaction effects between total serum cholesterol levels and statins on the risk of ICH. RESULTS: A total of 3492 cases (mean age, 73.0±12.7 years; males, 56.6%) and 3492 control subjects were enrolled. Increasing total serum cholesterol levels were confirmed to be inversely associated with ICH. We observed a statistical interaction between total serum cholesterol levels and statin use for the risk of haemorrhage (Interaction OR (IOR), 1.09; 95% CI 1.05 to 1.12). Increasing levels of total serum cholesterol were associated with a decreased risk of ICH within statin strata (average OR, 0.87; 95% CI 0.86 to 0.88 for every increase of 0.26 mmol/l of total serum cholesterol concentrations), while statin use was associated with an increased risk (OR, 1.54; 95% CI 1.31 to 1.81 of the average level of total serum cholesterol). The protective effect of serum cholesterol against ICH was reduced by statins in strictly lobar brain regions more than in non-lobar ones. CONCLUSIONS: Statin therapy and total serum cholesterol levels exhibit interaction effects towards the risk of ICH. The magnitude of such effects appears higher in lobar brain regions.

Cocaine dependence and stroke: pathogenesis and management.

Cocaine abuse remains a devastating medical problem for our society. Current concepts suggest that both hemorrhagic and ischemic stroke, particularly in young people, can result as a consequence of cocaine exposure. We provide an analysis of mechanisms of injury and a discussion of the pharmacological management of stroke following cocaine use. Preclinical research suggests that the cause of cocaine-mediated stroke is multifactorial and involves vasospasm, changes in cerebral vasculature, and platelet aggregation. We suggest that drugs able to induce vasospastic, thrombogenic, or neurotoxic effects of cocaine could be suitable as therapeutic agents. In contrast caution should be exerted when using anti-platelet and thrombolytic agents in cocaine users with stroke.

Prevalence of Patent Foramen Ovale in Ischaemic Stroke in Italy: Results of SISIFO Study.

BACKGROUND: Although several authors have studied the association between patent foramen ovale (PFO) and ischaemic stroke, the matter is still controversial; few have suggested an association between cryptogenetic stroke and PFO, while others have denied this association. The aim of this study was to evaluate PFO prevalence in the whole ischaemic stroke population, independently from age and stroke subtypes and to identify the characteristics associated with the presence of PFO. METHODS: SISIFO study was a multicenter, prospective, single-wave, cross-sectional survey conducted on consecutive patients with acute ischemic stroke admitted to selected clinical centres. Data regarding vascular risk factors were registered for each patient; all patients underwent computed tomography scan and/or magnetic resonance imaging of the brain; an electrocardiogram and standard laboratory blood tests were performed. A Doppler ultrasound study of extra-cranial arteries was performed too. The cases were classified according to TOAST and OCSP criteria. Each patient underwent transcranial Doppler or transcranial color-coded duplex sonography with bubble test as diagnostic tool for right-to-left-shunt. Where right-to-left shunt was detected, PFO presence was confirmed by echocardiography. FINDINGS: 1,130 consecutive patients were included. We found a PFO in 247 (21.9%; 95% CI, 19.5-24.3%) patients; PFO was present in 23.5% of patients with cryptogenic stroke and in 21.3% of patients with stroke of known causes; this difference was not statistically significant. At the univariate analysis, decreasing age, hypertension, diabetes mellitus, and atrial fibrillation, and stroke characteristics such as NIHSS, OCSP and TOAST were predictors of PFO presence. At the multivariate analysis, we found a significant interaction between age and OCSP syndrome. Being LACI the reference category, the prevalence of PFO in PACI and POCI decreased significantly along with age, whereas there was no change in TACI. CONCLUSION: If any relationship exists between stroke and PFO, this is more likely in PACI and POCI at a younger age. Our results are consistent with recent findings that underline PFO alone must not be considered a significant independent predictor for stroke; so the presence of PFO alone doesn't permit rushed causal correlations or 'therapeutic aggressiveness'.

Sonography of the optic nerve sheath beyond the hyperacute stage of intracerebral hemorrhage.

PURPOSE: To evaluate the feasibility and utility of serial measuring of the optic nerve sheath diameter beyond the hyperacute and acute stage of intracerebral hemorrhage (ICH). METHODS: Four patients with extensive ICH in the left basal ganglia were followed using ultrasound (US) and cerebral CT scans. RESULTS: Optic nerve sheath diameter values assessed beyond the acute stage of ICH showed a high correlation (ρ = 0.84, p = 0.0022) with midline shift of the third ventricle seen on CT scans. CONCLUSIONS: Optic nerve sonography can be useful to evaluate patients with extensive ICH beyond the acute stage and help monitoring clinical evolution in these patients, when ICP monitoring is not feasible.

A new assessment tool for Parkinson disease: the nigral lesion load obtained by transcranial sonography.

OBJECTIVES: A sonographic method that provides for the measurement of a single frozen image and ignores the remaining portions of the midbrain has been used recently as a biological marker of Parkinson disease. We propose a new approach to evaluating the midbrain: obtaining the nigral lesion load, with which it is possible to acquire an estimate of the real damage to the substantia nigra. METHODS: We studied 60 patients with Parkinson disease and classified them according to the Hoehn and Yahr scale (Neurology 1967; 17:427-442). Magnetic resonance imaging of the brain, ioflupane-labeled single-photon emission computed tomography, and technetium Tc 99m-labeled single-photon emission computed tomography were performed. Assessment of the midbrain parenchyma was performed with transcranial sonography to quantify the extent of hyperechoic signals on 2 different scans (upper and lower substantia nigra). RESULTS: In 90% of patients (54), we found pathologic hyperechoic substantia nigra signals (>0.25 cm(2)). These data were similar to those described previously by other authors. However, the sum of the values obtained from each measurement (total of 4 per patient) showed that patients with severe disease had larger nigral lesion loads. In most cases, the study showed impairment of the nigrostriatal dopaminergic system when the hyperechoic pattern was more pronounced. CONCLUSIONS: Transcranial sonography is a useful tool for Parkinson disease workup. A single measurement of substantia nigra echogenicity may be insufficient for an optimal definition of the stage of the disease. A study of the entire midbrain may deliver more information than a single measurement.

Cerebral stroke injury: the role of cytokines and brain inflammation.

Stroke represents the most frequent cause of permanent disability in adults worldwide. Cerebral ischemia triggers the pathological pathways of the ischemic cascade and causes irreversible neuronal injury in the ischemic core within minutes of the onset. Elements of the immune system are involved in all stages of ischemic cascade from acute intravascular events triggered by the interruption of blood supply, to the parenchymal processes leading to brain damage and to the ensuing tissue repair. In this review, we will provide a brief overview of current understanding of the role of cytokines and brain inflammation during acute ischemic stroke.