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Background and purpose This case illustrates for the first time the clinical and radiological evolution of SARS‐CoV‐2 meningo‐encephalitis. Methods A case of a SARS‐CoV‐2 meningo‐encephalitis is reported. Results A 65‐year‐old man with COVID‐19 presenting with meningo‐encephalitis without respiratory involvement is described. He had fever, diarrhea and vomiting, followed by diplopia, urinary retention and sleepiness. Examination disclosed a convergence strabismus and ataxia. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis, oligoclonal bands and increased interleukin 6 level. SARS‐CoV‐2 was detected in the CSF through reverse transcriptase polymerase chain reaction, but not in nasopharyngeal, tracheal secretion and rectal samples. Brain magnetic resonance imaging showed lesions on white matter hemispheres, the body and splenium of the corpus callosum and resembling the projection of corticospinal tract, remarkably on cerebellar peduncles. Conclusions This demonstrates the challenges in diagnosing COVID‐19 in patients with neurological presentations., Brain magnetic resonance imaging evolution image of COVID‐19 meningo‐encephalitis.

The coronavirus 2019 (COVID-19) pandemic affected stroke care worldwide. Data from low- and middle-income countries is limited.What was the impact of the pandemic in intensive care admissions and outcomes of patients with stroke, in comparison to trends over the last ten years?Retrospective cohort study including prospectively collected data from 165 ICUs in Brazil between 2011 and 2020. We analyzed clinical characteristics and mortality over a period of 10 years and evaluated the impact of the pandemic on stroke outcomes using the following approach: analyses of admissions for ischemic and hemorrhagic strokes and trends in in-hospital mortality over ten years; analysis of variable life-adjusted display (VLAD) during 2020; and a mixed-effects multivariable logistic regression model.17,115 stroke admissions were analyzed, from which 13,634 were ischemic and 3,481 were hemorrhagic. In-hospital mortality was lower after ischemic stroke as compared to hemorrhagic (9% vs. 24%, respectively). Changes in VLAD across epidemiological weeks of 2020 showed that the rise in COVID-19 cases was accompanied by increased mortality, mainly after ischemic stroke. In logistic regression mixed models, mortality was higher in 2020 compared to 2019, 2018, and 2017 in patients with ischemic stroke, namely in those without altered mental status. In hemorrhagic stroke, the increased mortality in 2020 was observed in patients 50 years or younger, as compared to 2019.Hospital outcomes of stroke admissions worsened during the COVID-19 pandemic, interrupting a trend of improvements in survival rates over 10 years. This effect was more pronounced during the surge of COVID-19 ICU admissions affecting predominantly patients with ischemic stroke without coma, and young patients with hemorrhagic stroke.

Chagas disease and ischemic stroke (IS) have a close but poorly understood correlation. In endemic settings, continued transmission over time has resulted in increasing prevalence of both asymptomatic infection and cardiomyopathy with increasing age. Latin America has made substantial progress towards Chagas disease control. Although several epidemiological studies have been conducted, information regarding epidemiology and distribution of IS in Chagas disease is still lacking. We retrospectively studied the electronic medical record data of all patients with both IS and Chagas disease admitted at SARAH Hospitals across Brazil from 2009 to 2013 to make epidemiological quantifications and statistical inferences. A total of 279 patients with Chagas disease and IS were analyzed from 7729 IS-related admissions, indicating a median prevalence of 3.6% of Chagas disease in IS patients in our cohort. Mean age was 60 years, with female predominance (65%). Most of the cases were from Bahia (61%), followed by Minas Gerais (19%) and Goias (9.7%). Low-income cities, with decreased access to healthcare, showed the highest number of cases. Distribution of vascular risk factors and outcome after stroke differed among the units. According to current guidelines, secondary prevention was inadequate in 60% of patients. Chagas disease was common in IS patients; prevalence of concurrent Chagas disease and IS was high in some regions of the country. However, the infection frequency seems to be reduced in the last few years. Public health issues for improving the treatment of Chagas disease and IS are urgently needed.

Background Chagas disease (CD) and ischemic stroke (IS) have a significant but poorly understood correlation. There is paucity of evidence regarding secondary prophylaxis of IS and etiological causes. Objectives To compare arterial stroke topography and the respective morbidities and mortality in patients with CD of undetermined and cardioembolic etiologies and with cardioembolic IS (atrial fibrillation [AF]). Methods We compared vascular topography and outcomes using data obtained from the electronic medical records of all patients with IS with either CD (with cardioembolic or undetermined etiology) or AF, admitted to SARAH Hospital Brasilia between 2009 and 2013. Results A total of 115 patients were investigated: 49 involving AF, 23 involving CD of unclear etiology, and 43 involving CD of cardioembolic etiology. Middle cerebral artery stroke was predominant in all groups, although more frequent in patients with CD of undetermined etiology. No significant difference was found in the arterial territories. Hemodynamic stroke was predominant among CD patients who experienced cardioembolic events. AF patients had worse modified Rankin scale scores upon admission and a higher mortality rate than CD patients in both categories. Conclusions Stroke topography is not useful in determining the etiological diagnosis. Patients with AF and IS are more likely to have worse outcomes than are those with CD and IS. The autonomic nervous system could be affected in patients with CD.

Background RESILIENT is a prospective, multicenter, randomized phase III trial to test the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. Methods Subjects must fulfill the following main inclusion criteria: symptom onset ≤8 h, age ≥18 years, baseline NIHSS ≥8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS ≥6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. Randomization Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. Design The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0–2 at 90 days) common odds ratio of 1.615. Primary outcome Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. Secondary outcomes Secondary end-points include: 90-day functional independence (mRS ≤2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0–2 or improvement ≥8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.

Background: Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. Summary: The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.

Introduction: Although the 2019 severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2, COVID-19) pandemic poses new challenges to the healthcare system to provide support for thousands of patients, there is special concern about common medical emergencies, such as stroke, that will continue to occur and will require adequate treatment. The allocation of both material and human resources to fight the pandemic cannot overshadow the care for acute stroke, a time-sensitive emergency that with an inefficient treatment will further increase mortality and long-term disability. Objective: This paper summarizes the recommendations from the Scientific Department on Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Society of Cerebrovascular Diseases and the Brazilian Society of Neuroradiology for management of acute stroke and urgent neuro-interventional procedures during the COVID-19 pandemic, including proper use of screening tools, personal protective equipment (for patients and health professionals), and patient allocation.

Background and purpose: RESILIENT Trial was the first study in a developing country to demonstrate the benefit of mechanical thrombectomy (MT) in acute stroke patients. This economic evaluation aimed to access the cost-utility of MT under the perspective of the Brazilian Public Healthcare System. Methods: Analysis was based on a subset sample of the original study (151 of 221 patients) from 4 hospitals. We compared costs and utilities between MT plus standard care (n=78) vs. standard care alone (n=73). Direct medical costs were considered, and utilities were inputted according to each patient’s Utility-Weighted modified Rankin Score (UW-mRS). First-year survival was obtained from trial follow-up and modelled for a life-time horizon adjusted by National Mortality Data. Direct medical costs were converted to I$ using Purchasing Power Parity (PPP). A discount rate of 5% was used. Incremental cost-effectiveness ratio (ICER) is expressed in cost (I$) per Quality-Adjusted Life Year (QALY). Results: RESILIENT trial was stopped on its first interim analysis because of early efficacy. The incremental costs and QALYs gained with MT were estimated at I$ 8,369 and 0.75, respectively, compared with standard medical care, yielding an incremental cost-effectiveness ratio (ICER) of I$ 7,256 per QALY. Conclusion: The initially higher costs of MT were offset by the clear benefit of the intervention. RESILIENT trial demonstrated that such therapy is likely to be cost-effective despite the economical constraints in the Brazilian healthcare system.

Introduction: In randomized clinical trials, central adjudication is frequently used for study outcomes. However, stroke trials have historically used site-derived Rankin scale assessments as primary outcome. Hypothesis: A central adjudication of Rankin scale assessment is at least as accurate as site-derived assessment. Methods: We studied acute stroke survivors from the RESILIENT study, where primary outcome was the consensus Rankin scale rating of two blinded central adjudicators who independently watched video recordings of a 90-day post-stroke structured patient and/or family interview. We compared agreement rates (weighted kappa statistics) between both central adjudicators with that between the blinded site investigator and the consensus reading between central adjudicators. Results: Trial randomized 221 patients to thrombectomy or medical treatment alone. At 90 days, 161 (73%) survived and 142/161 (88%) had quality video recordings for central adjudicators. Median (interquartile range) Rankin scores were similarly 3 (2-4) for each central rater and for the site investigators. Agreement rates between central adjudicators was 79.6% (kappa=0.94, p Conclusions: Central blinded Rankin scale outcome assessment is feasible and is at least as good as site investigator assessments. For open-label trials with blinded clinical outcome assessment, central adjudication of video-recorded interviews provides safer blinding and accountability.

Background: Despite evidence supporting the overall efficacy of mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) of the anterior circulation, it is unclear whether the treatment effect of MT differs by sex in different populations. We assessed the impact of sex differences in the treatment effect of MT in the RESILIENT trial. Methods: RESILIENT was a prospective, multicenter, randomized phase III trial that was designed to assess the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. Results: Among 221 patients enrolled in the trial, 104 (47,1%) were female. Baseline characteristics were well balanced between sexes, except for a higher prevalence of hypertension (76% vs. 57.4%; p=0.004) and diabetes (34.3% vs. 21.7%; p=0.039) and a lower frequency of alcohol abuse (4% vs. 28.9%; p=0.001) in females. After adjustment for baseline characteristics, we found a significant interaction (p=0.026) between sex and the effect of MT with a lower efficacy of MT for functional independency at 90 days among women (aOR=1.13;95%CI:0.42-3.02) compared to men (aOR=4.78; 95%CI:1.88-12.15). Conclusions: In our study population of patients with AIS caused by LVO of the anterior circulation, women were less likely to benefit from MT than men. Further studies are necessary to investigate these findings.

Background: CT perfusion has been increasingly used as a selection tool in acute reperfusion therapies. However, it remains unknown whether its use is associated with a higher treatment benefit in patients undergoing thrombectomy. We sought to evaluate the interaction between imaging selection modalities and treatment effect in the RESILIENT Trial. Methods: RESILIENT was a randomized, prospective, multicenter, controlled trial evaluating the safety, efficacy, and cost-effectiveness of thrombectomy versus medical treatment alone in Brazil. A total of 221 patient were enrolled. The trial showed a strong benefit of thrombectomy (90-day mRS ordinal shift, OR 2.28 95%CI [1.41-3.70]; p=0.001). Key imaging selection criteria included ASPECTS ≥6 on non-contrast CT (NCCT) and the exclusion of malignant collateral profile on CT angiography. The use of automated CT perfusion software (RAPID, IschemaView) was optional but was made available in some centers with the pre-specified plan to compare imaging selection modalities. The primary end-point was the common odds ratio (cOR) of mRs at 90 days (shift analysis) and the main secondary endpoint was the rate of functional independence (mRS 0-2) at 90 days. Ordinal logistic and binary regression analyses with imaging selection modality (NCCT versus CTP) as an interaction term were performed with adjustments for potential confounders including age, baseline NIHSS score, occlusion site, IV tPA use and ASPECTS. A p value < 0.05 was considered statistically significant. Results: CTP was performed in 41% of the thrombectomy group and 45% in the control group. There was no significant difference in the treatment effect size for patients selected on the basis of NCCT and CTA only versus those submitted to CTP in terms of overall functional disability (ordinal mRS shift: aOR: 2.87, 95%CI [1.47-5.61] vs. 2.10, 95%CI [1.01-4.36]; p=0.390) or functional independence (mRS 0-2: aOR: 3.16, 95%CI [1.32-7.57] vs. 2.54 95%CI [0.86-7.49], p=0.40) at 90 days. Conclusion: In a randomized clinical trial of thrombectomy within 8 hours of stroke onset, there was no evidence of difference in the treatment effect size across patients selected with NCCT and CTA alone versus automated CT perfusion software.

Summary Background S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov , NCT02877615 . Findings Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding Servier.

Background: Chagas disease is related to ischemic stroke (IS), although few epidemiological studies have evaluated the associated mortality and recurrence. Our objective is to determine factors associated with mortality and recurrence of IS in patients with IS and Chagas disease. Methods: We retrospectively studied data obtained from electronic medical records of patients admitted at SARAH Hospitals across Brazil between 2009 and 2013. Using Cox regression analysis for mortality and logistic regression for recurrence, we assessed primary population characteristics and statistical associations between risk factors and outcomes. Results: We analyzed 279 patients who were followed up until 2016. The mean age at stroke onset was 61 with a 10% frequency of death. Multivariate analysis assessing mortality demonstrated that the associated factors were age at stroke (hazard ratio [HR] 1.04), initial modified Rankin Scale (mRS; HR 20.91), bladder dysfunction (HR 2.51), diabetes mellitus (DM; HR 3.64), and alcoholism (HR 3.37). Multivariate analysis assessing recurrence demonstrated that the associated factors were age at ictus (OR 0.96), cognitive deficit (OR 0.44), initial mRS (OR 1.84), cardioembolic etiology (OR 2.47), and female sex (OR 2.73). Conclusions: Cardiac conditions did not correlate with mortality or recurrence. Age was a protective factor against recurrence, probably due to cumulative risk of IS over time, while initial mRS was associated with both outcomes. Treating diseases such as DM and bladder dysfunction, and early treatment to reduce the initial mRS could potentially prevent both outcomes; also, establishing a correct etiological diagnosis is important.

Background Chagas disease (CD) and ischemic stroke (IS) have a close, but poorly understood, association. There is paucity of evidence on the ideal secondary prophylaxis and etiological determination, with few cardioembolic patients being identified. Aims This study aimed to describe a multicenter cohort of patients with concomitant CD and IS admitted in tertiary centers and to create a predictive model for cardioembolic embolism in CD and IS. Materials and methods We retrospectively studied data obtained from electronic medical and regular medical records of patients with CD and IS in several academic, hospital-based, and university hospitals across Brazil. Descriptive analyses of cardioembolic and non-cardioembolic patients were performed. A prediction model for cardioembolism was proposed with 70% of the sample as the derivation sample, and the model was validated in 30% of the sample. Results A total of 499 patients were analyzed. The median age was similar in both groups; however, patients with cardioembolic embolism were younger and tended to have higher alcoholism, smoking, and death rates. The predictive model for the etiological classification showed close relation with the number of abnormalities detected on echocardiography and electrocardiography as well as with vascular risk factors. Conclusions Our results replicate in part those previously published, with a higher prevalence of vascular risk factors and lower median age in patients with cardioembolic etiology. Our new model for predicting cardioembolic etiology can help identify patients with higher recurrence rate and therefore allow an optimized strategy for secondary prophylaxis.

Background The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. Patients and methods Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as “benign” or “likely benign” in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database ( n = 33,370). Results Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8–52.9). Conclusion Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

Importance Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging, especially in low- and middle-income countries. Objective To assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for care of patients with AIS and TIA. Design, Setting and Participants This 2-arm cluster-randomized clinical trial assessed 45 hospitals and 2336 patients with AIS and TIA for eligibility before randomization. Eligible hospitals were able to provide care for patients with AIS and TIA in Brazil, Argentina, and Peru. Recruitment started September 12, 2016, and ended February 26, 2018; follow-up ended June 29, 2018. Data were analyzed using the intention-to-treat principle. Interventions The multifaceted quality improvement intervention included case management, reminders, a roadmap and checklist for the therapeutic plan, educational materials, and periodic audit and feedback reports to each intervention cluster. Main Outcomes and Measures The primary outcome was a composite adherence score for AIS and TIA performance measures. Secondary outcomes included an all-or-none composite end point of performance measures, the individual process measure components of the composite end points, and clinical outcomes at 90 days after admission (stroke recurrence, death, and disability measured by the modified Rankin scale). Results A total of 36 hospitals and 1624 patients underwent randomization. Nineteen hospitals were randomized to the quality improvement intervention and 17 to routine care. The overall mean (SD) age of patients enrolled in the study was 69.4 (13.5) years, and 913 (56.2%) were men. Overall mean (SD) composite adherence score for the 10 performance measures in the intervention group hospitals compared with control group hospitals was 85.3% (20.1%) vs 77.8% (18.4%) (mean difference, 4.2%; 95% CI, −3.8% to 12.2%). As a secondary end point, 402 of 817 patients (49.2%) at intervention hospitals received all the therapies that they were eligible for vs 203 of 807 (25.2%) in the control hospitals (odds ratio, 2.59; 95% CI, 1.22-5.53;P = .01). Conclusions and Relevance A multifaceted quality improvement intervention did not result in a significant increase in composite adherence score for evidence-based therapies in patients with AIS or TIA. However, when using an all-or-none approach, the intervention resulted in improved adherence to evidence-based therapies. Trial Registration ClinicalTrials.gov identifier:NCT02223273

Background: The role of patent foramen ovale is a field of debate and current publications have increasing controversies about the patients’ management in young undetermined stroke. Work up with echocardiography and transcranial Doppler (TCD) can aid the decision with better anatomical and functional characterization of right-to-left shunt (RLS). Medical and interventional strategy may benefit from this information. Summary: a group of experts from the Latin American participants of the Neurosonology Research Group (NSRG) of World Federation of Neurology created a task force to review literature and describe the better methodology of contrast TCD (c-TCD). All signatories of the present consensus statement have published at least one study on TCD as an author or co-author in an indexed journal. Two meetings were held while the consensus statement was being drafted, during which controversial issues were discussed and voted on by the statement signatories. The statement paper was reviewed and approved by the Executive Committee of the NSRG of the World Federation of Neurology. The main objective of this consensus statement is to establish a standardization of the c-TCD technique and its interpretation, in order to improve the informative quality of the method, resulting in expanding the application of TCD in the clinical setting. These recommendations optimize the comparison of different diagnostic methods and encourage the use of c-TCD for RLS screening and complementary diagnosis in multicenter studies.

The present article provides the historical background of the Sociedade Brasileira de Doenças Cerebrovasculares (Brazilian Society for Cerebrovascular Diseases), including details on its function, structure, challenges and main achievements. RESUMO O presente texto apresenta um relato histórico da Sociedade Brasileira de Doenças Cerebrovasculares, incluindo detalhes da sua fundação, estruturação, dificuldades e principais realizações.

Background Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging especially in low- and middle-income countries. Objectives The aim of this study is to assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for AIS and TIA patients care. Design We designed a pragmatic, 2-arm cluster-randomized trial involving 36 clusters and 1624 patients from Brazil, Argentina, and Peru. Hospitals are randomized to receive a multifaceted quality improvement intervention (intervention group) or to routine care (control group). The BRIDGE Stroke multifaceted quality improvement intervention includes case management, reminders, health care providers’ educational materials (including treatment algorithms), interactive workshops, and audit and feedback reports. Primary outcome is a composite adherence score to AIS and TIA performance measures. Secondary outcomes include an “all or none” composite end point to performance measures, the individual components of the composite end points, and clinical outcomes at 90 days following admission (stroke recurrence, death, and disability measured by the modified Rankin scale). Summary The BRIDGE Stroke Trial is an international pragmatic evaluation of a multifaceted quality improvement intervention. If effective, this intervention could be potentially extended widely to improve the quality of care and outcomes of patients with AIS or TIA.

Ischemic stroke (IS) and Chagas disease are strongly related. Nevertheless, little attention has been paid to this association and its natural history. The current guidelines concerning the management and secondary prevention of IS are largely based on the incomplete information or extrapolation of knowledge from other stroke etiologies. We performed a retrospective study which compared stroke etiologies among a cohort of hospitalized patients with IS and Chagas disease. The Instituto de Pesquisa Evandro Chagas/Fundacao Oswaldo Cruz (IPEC/FIOCRUZ) embolic score was also used to identify and evaluate the risk of embolism in this population. A total of 86 patients were included in the analysis. The mean age of the study population was 58 years, and 60 % were men. According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) Classification, 45 % of the strokes were of undetermined etiology and 45 % of cardioembolic origin, while the Stop Stroke Study/Causative Classification System (SSS/CCS) TOAST indicated that 34 % were undetermined and 50 % cardioembolic (p

Introduction: The organization of the stroke care in Brazil started in 2002 after the tPA approval. In 2008, was started a task force of stroke neurologists together with the Ministry of Health (MOH) with the objective of supporting the establishment of a nationwide network. Since then, the hospitals have progressively improved their structure. In 2012, was launched the National Stroke Policy, by the MOH, with creation of stroke centers in public health system, reimbursement of tPA, implementation of telemedicine and creation of the Line of Care integrating all stroke assistance. The aim of this study is to compare the structure of stroke care in 2008 and 2017. Method: This cross-sectional study compared the structure of stroke centers in 2008 and 2017. The information was collected through online questionnaires sent to the stroke centers and to the vascular neurologists. Results: In 2008, 35 stroke centers were active (40% assisting public health patients), only 14% with stroke units and no hospital had telemedicine. The National Emergency Medical Service (EMS) was trained in 4 cities, covering 23% of stroke centers. In 2017, there are 139 stroke centers registered in Brazil. We had answers from 110 hospitals (79%) in 15 out of 26 states (9 states do not have stroke centers). The EMS covers 96% of the stroke centers but only 63% is linked with the local network. The centers are 34% public, 42% private and 24% assist both public and private patients (58% assist public health system). The stroke units are present in 49% of hospitals. Neurologists are available 24h /7 days a week in 82% of the hospitals (33% on duty, 44% on call and 23% by telemedicine). In total, 41% of hospitals are comprehensive stroke centers. As the thrombectomy devices are not paid in the public hospitals, only 2 are comprehensive stroke centers, 8 had structure but not devices and are participating in a clinical trial to approve thrombectomy in public hospitals in Brazil. Conclusion: The organization of stroke care in Brazil has improved a lot in recent years. Despite this, we have a lot to improve, since it’s still a small number of hospitals for a huge country, with large part of its population without access to the best treatments.

Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.

Aims: To assess the biodistribution of bone marrow mononuclear cells (BMMNC) delivered by different routes in patients with subacute middle cerebral artery ischemic stroke. Patients & methods: This was a nonrandomized, open-label Phase I clinical trial. After bone marrow harvesting, BMMNCs were labeled with technetium-99m and intra-arterially or intravenously delivered together with the unlabeled cells. Scintigraphies were carried out at 2 and 24 h after cell transplantation. Clinical follow-up was continued for 6 months. Results: Twelve patients were included, between 19 and 89 days after stroke, and received 1-5 × 10 8 BMMNCs. The intra-arterial group had greater radioactive counts in the liver and spleen and lower counts in the lungs at 2 and 24 h, while in the brain they were low and similar for both routes. Conclusion: BMMNC labeling with technetium-99m allowed imaging for up to 24 h after intra-arterial or intravenous injection in stroke patients.

Migraine and ischemic strokes are two of the most prevalent diseases worldwide. Besides having a coincident symptomatology, for long researchers have been searching for a possible causal relation between these diseases. Current evidence based on data suggest that patients with aura migraine could have a doubled risk of developing an ischemic stroke, when compared to the rest of the population. At the same time, migraine sufferers apparently have higher incidences of risk factors for cardiovascular events. The aim of this review was not only to dissect some of the more compelling evidence based on data regarding this association, but also to discuss the possible clinical and therapeutic implications.Migrânea e acidentes vasculares cerebrais isquêmicos (AVCI) são duas das doenças de maior prevalência em todo o mundo. Além de apresentarem alguns sintomas em comum, há muito tempo pesquisadores procuram investigar uma relação causal entre as duas. As informações atuais baseadas em evidência sugerem que pacientes com migrânea com aura podem ter um risco duas vezes maior de desenvolver AVCI, quando comparados com o restante da população. Ao mesmo tempo, aqueles sofrem de migrânea possuem aparentemente maior incidência de fatores de risco para eventos cardiovasculares. O objetivo desta revisão foi não apenas avaliar grande parte das mais importantes e convincentes evidências científicas sobre esta associação, mas também discutir suas possíveis implicações clínicas e terapêuticas.

Although the prevalence of neuropsychiatric disorders among patients with cerebrovascular illness is relatively high, there are only few case reports describing post-stroke psychotic symptoms. In general, post-stroke psychoses have been reported to emerge few days after the vascular event and to vanish soon afterwards. In this report, we describe delayed-onset post-stroke delusional disorder, persecutory type. A middle-aged female patient developed a persistent delusional disorder with homicidal behavior about one year after a cerebrovascular accident affecting the right fronto-temporo-parietal region and a long period of chronic post-stroke mixed anxiety and depressive symptoms. Our case suggests that there might be long intervals between stroke and the appearance of psychotic symptoms.

Background and Purpose— Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). b-vitamin supplementation with folate and vitamins b 12 and b 6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of b vitamins would reduce the progression of CSVD-related brain lesions. Methods— A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of b-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of b-vitamin supplementation on the incidence of other ischemic abnormalities. Results— After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13cm 3 ; P =0.419) and incidence of lacunes (8.0% vs 5.9%, P =0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7cm 3 ; P =0.039). Conclusions— Daily b-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. Clinical Trial Registration— http://vitatops.highway1.com.au/ . Unique identifier: NCT00097669 and ISRCTN74743444.

Made available in DSpace on 2018-11-28T03:37:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01. Added 1 bitstream(s) on 2019-10-09T18:27:35Z : No. of bitstreams: 1 S0004-282X2017000100050.pdf: 155772 bytes, checksum: c55550248854584f7b2472bcb06a538a (MD5) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Brazilian Ministry of Health (Decit/SCTIE/MS) These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil. Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP, Brazil Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil Emory Univ, Sch Med, Grady Mem Hosp, Marcus Stroke & Neurosci Ctr, Atlanta, GA USA Univ Fed Sao Paulo, Sao Paulo, SP, Brazil Hosp Base Brasilia, Brasilia, DF, Brazil Univ Sao Paulo, Fac Med, Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Med Botucatu, Botucatu, SP, Brazil Hosp Pro Cardiaco, Rio De Janeiro, RJ, Brazil Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil Univ Fed Fluminense, Niteroi, RJ, Brazil Inst Dor Pesquisa & Ensino, Rio De Janeiro, RJ, Brazil Hosp Municipal Sao Jose, Div Neurol, Joinville, SC, Brazil Hosp Geral Fortaleza, Fortaleza, Ceara, Brazil Hosp Restauracao, Recife, PE, Brazil Hosp Sirio Libanes, Sao Paulo, SP, Brazil Univ Fed Bahia, Salvador, BA, Brazil Santa Casa Sao Paulo, Fac Ciencias Med, Sao Paulo, SP, Brazil Hosp Israelita Albert Einstein, Sao Paulo, SP, Brazil Univ Estadual Paulista, Fac Med Botucatu, Botucatu, SP, Brazil CNPq: 402388/2013-5 CNPq: 467322/2014-7

Background Fever is commonly observed in patients who have had aneurysmal subarachnoid hemorrhage (SAH), and it has been associated with the occurrence of delayed cerebral ischemia and worse outcomes in previous studies. Frequently, fever is not the result of bacterial infections, and distinction between infection-related fever and fever secondary to brain injury (also referred as central fever) can be challenging. Objectives The current study aimed to identify risk factors on admission for the development of central fever in patients with SAH. Methods Databank analysis was performed using information from demographic data (age, gender), imaging (transcranial Doppler ultrasound, computed tomography, and cerebral angiogram), laboratory (white blood cell count, hemoglobin, renal function, and electrolytes), and clinical assessment (Hunt–Hess and modified Fisher scales on admission, occurrence of fever). A multivariate logistic regression model was created. Results Of 55 patients, 32 developed fever during the first 7 days of hospital stay (58%). None of the patients had identifiable bacterial infections during their first week in the neurocritical care unit. Hunt–Hess scale >2 and leukocytosis on admission were associated to the development of central fever, even after correction in a logistic regression model. Conclusion Leukocytosis and a poor neurologic examination on admission might help predict which subset of patients with SAH are at higher risk of developing central fever early in their hospital stay.

Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality, but currently no single clinical method or ancillary test can reliably predict which subset of patients will develop delayed cerebral ischemia (DCI). The aim of this study was to find hematologic derangements and clinical factors present during the first 7 days after bleeding that could help identify patients at risk for development of DCI.Databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. Data from demographics, imaging, laboratory, and clinical factors were collected. Statistical testing was conducted to test for association to the outcome, and multivariate logistic regression was used to design a predictive model.Of 55 patients, 14 developed DCI (25%). Anemia and leukocytosis on the third day after bleeding were significantly correlated with the outcome (for anemia: P.032; confidence interval, 1.12-15.16; odds ratio, 4.12; for leukocytosis: P.046; confidence interval, 1.03-26.13; odds ratio, 5.18). Anemia and leukocytosis were still statistically significant after adjustment for age, sex, modified Fisher scale, and Hunt-Hess scale.The presence of leukocytosis and anemia during the third day after SAH was statistically correlated with the occurrence of DCI.

Background: It is not well understood whether age impacts transcranial Doppler (TCD) mean flow velocities (MFVs) in patients with aneurysmal subarachnoid hemorrhage (SAH) with or without delayed cerebral ischemia (DCI). The aim of our study was to analyze the behavior of TCD MFV during the first 7 days after SAH in patients of different ages and correlate them with the occurrence of DCI. Methods: This study is a databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. We analyzed mean MFV of bilateral middle cerebral arteries (MCAs) in all patients enrolled in the study on days 1, 3 and 7. The correlation between age and TCD MFV was analyzed using a univariate linear regression model. Results: Fifty-five patients were studied. Starting on the third day after the bleeding, increasing age was associated with slower MFVs. This trend was not affected by the interrogation of the right or left MCA. After correction to include only patients who developed DCI, the same findings persisted on days 3 and 7. Conclusion: Older age was correlated with a significant decrease on TCD velocities in patients with SAH, even after correction for patients who developed DCI.

Stroke is the second leading cause of mortality worldwide, causing millions of deaths annually, and is also a major cause of disability-adjusted life years. Hemorrhagic stroke accounts for approximately 10 to 27% of all cases and has a fatality rate of about 50% in the first 30 days, with limited treatment possibilities. In the past two decades, the therapeutic potential of bone marrow-derived cells (particularly mesenchymal stem cells and mononuclear cells) has been intensively investigated in preclinical models of different neurological diseases, including models of intracerebral hemorrhage and subarachnoid hemorrhage. More recently, clinical studies, most of them small, unblinded, and nonrandomized, have suggested that the therapy with bone marrow-derived cells is safe and feasible in patients with ischemic or hemorrhagic stroke. This review discusses the available evidence on the use of bone marrow-derived cells to treat hemorrhagic strokes. Distinctive properties of animal studies are analyzed, including study design, cell dose, administration route, therapeutic time window, and possible mechanisms of action. Furthermore, clinical trials are also reviewed and discussed, with the objective of improving future studies in the field.

Although cerebrovascular diseases are among the leading causes of health burden in the world, presently existing therapies have narrow capabilities in the treatment of such ailments [1, 2]. Cell therapies were originally used in hematological disorders and are currently being investigated as potential treatments for diverse conditions [3, 4]. Several preclinical reports have indicated that cell transplantation may generate beneficial functional and structural outcomes in stroke animals, even though the underlying mechanisms for such effects are still the subject of intensive research [5–7]. In the clinical setting, preliminary studies have been published indicating a good safety profile of systemic cell therapies, but additional trials are needed to assess the possible feasibility and efficacy of cell transplantation in cerebrovascular patients [5, 8, 9]. Furthermore, there are numerous obstacles to be tackled in order to thoroughly translate results from animal studies to patients [5, 8, 9].

DIABETES MELITO A medida da PA no consultorio em pacientes com diabetes melito (DM) deve ser feita nas posicoes supina e ortostatica em funcao da maior ocorrencia de hipotensao ortostatica1 (C4). Por se tratar de pacientes de alto risco para eventos cardiovasculares, as metas a serem atingidas devem ser 130/80 mmHg2,3 (A1). Estudos demonstraram nao haver beneficios adicionais com reducao da PA, em diabeticos, inferior a esses valores4 (A1). A avaliacao inicial pode ser estabelecida por meio da medicao em duplicata da razao [...]

Patent foramen ovale (PFO), a relatively common abnormality in adults, has been associated with migraine. Few studies also linked PFO with cluster headache (CH). To verify whether right-to-left shunt (RLS) is related to headaches other than migraine and CH, we used transcranial Doppler following microbubbles injection to detect shunts in 24 CH, 7 paroxysmal hemicrania (PH), one SUNCT, two hemicrania continua (HC) patients; and 34 matched controls. RLS was significantly more frequent in CH than in controls (54% vs. 25%, p=0.03), particularly above the age of 50. In the HC+PH+SUNCT group, RLS was found in 6 patients and in 2 controls (p=0.08). Smoking as well as the Epworth Sleepiness Scale correlated significantly with CH, smoking being more frequent in patients with RLS. PFO may be non-specifically related to trigeminal autonomic cephalalgias and HC. The headache phenotype in PFO patients probably depends on individual susceptibility to circulating trigger factors.O forame oval patente (FOP), uma anormalidade cardíaca relativamente comum em adultos, tem sido associado à enxaqueca, mas raramente às cefaléias trigêmino-autonômicas (TACs). Utilizamos o Doppler transcraniano (DTC) para detecção de shunt direito-esquerdo (SDE) em 24 pacientes com cefaléia em salvas (CS), sete com hemicrania paroxística (HP), dois com hemicrania continua (HC) e um com SUNCT; alem de 34 controles. O SDE foi mais frequente nos pacientes com CS do que nos controles (54% vs. 25% p=0,03), particularmente acima de 50 anos. No grupo HP+HC+SUNCT, o SDE foi encontrado em seis pacientes e dois controles (p=0,08). O hábito de fumar, bem como sonolência excessiva diurna foram mais frequentes em paciente com CS. O FOP pode ter importância inespecífica na fisiopatologia das TACs e HC, na dependência da susceptibilidade individual a fatores desencadeantes.

Cell-based treatments have been considered a promising therapy for neurological diseases. However, currently there are no clinically available methods to monitor whether the transplanted cells reach and remain in the brain. In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m ( 99m Tc) in a cell-based therapy clinical study for chronic ischemic stroke. Six male patients (ages 24–65 years) with ischemic cerebral infarcts within the middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose ranged from 1.25 × 10 8 to 5 × 10 8 . Approximately 2 × 10 7 cells were labeled with 99m Tc and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA. None of the patients showed any complications on the 120-day follow-up. Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h, while the remaining uptake was mainly distributed to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake in Single-Photon Emission Computed Tomography (SPECT) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infarct in all patients. However, at 24 h homing could only distinguished in the brains of 2 patients, while in all patients uptake was still seen in the other organs. Taken together, these results indicate that labeling of BMMCs with 99m Tc is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 h.