The impact of experimental diabetes on intracerebral haemorrhage. A preclinical study.

Although diabetes mellitus negatively affects post-ischaemic stroke injury and recovery, its impact on intracerebral haemorrhage (ICH) remains uncertain. This study aimed to investigate the effect of experimental diabetes (ED) on ICH-induced injury and neurological impairment. Sprague-Dawley rats were induced with ED 2 weeks before ICH induction. Animals were randomly assigned to four groups: 1)Healthy; 2)ICH; 3)ED; 4)ED-ICH. ICH and ED-ICH groups showed similar functional assessment. The ED-ICH group exhibited significantly lower haemorrhage volume compared with the ICH group, except at 1 mo. The oedema/ICH volume ratio and cistern displacement ratio were significantly higher in the ED-ICH group. Vascular markers revealed greater expression of α-SMA in the ED groups (ED and ED-ICH) compared with ICH. Conversely, the ICH groups (ED-ICH and ICH) exhibited higher levels of VEGF compared to the healthy and ED groups. An assessment of myelin tract integrity showed an increase in fractional anisotropy in the ED and ED-ICH groups compared with ICH. The ED group showed higher cryomyelin expression than the ED-ICH and ICH groups. Additionally, the ED groups (ED and ED-ICH) displayed higher expression of MOG and Olig-2 than ICH. As for inflammation, MCP-1 levels were significantly lower in the ED-ICH groups compared with the ICH group. Notably, ED did not aggravate the neurological outcome; however, it results in greater ICH-related brain oedema, greater brain structure displacement and lower haemorrhage volume. ED influences the cerebral vascularisation with an increase in vascular thickness, limits the inflammatory response and attenuates the deleterious effect of ICH on white matter integrity.

Keeping prior anticoagulation treatment in the acute phase of ischaemic stroke: the REKOALA study.

INTRODUCTION: A consensus on the management of anticoagulated patients in the acute phase of ischaemic stroke has not yet been established. We aimed to evaluate clinical outcomes in such patients based on the continuation or discontinuation of anticoagulation. METHODS: Retrospective study of patients with acute ischaemic stroke and cardioembolic source receiving anticoagulant therapy is done. Patients were classified based on the continuation or discontinuation of anticoagulation at admission. Clinical outcomes, haemorrhagic and ischaemic events were assessed. Multivariate logistic regression analysis, propensity score matching (PSM) analysis and a sub-analysis of patients with severe ischaemic stroke at admission (NIHSS score ≥ 15) were performed. RESULTS: Anticoagulation was continued in 147 (78.8%) of 186 patients. Patients continuing anticoagulant had lower NIHSS (median 5 vs 18, p < 0.001). There were no differences in haemorrhagic or ischaemic events. In the multivariate analysis, good functional outcome at discharge was higher in the continuation group, OR (CI95%) 3.77 (1.2-11.2). PSM analysis adjusted for potential confounders such as NIHSS had higher rates of good functional outcomes at discharge (80% vs 36%, p = 0.004) and at 90 days (76% vs 44%, p = 0.042) in the continuation group. Patients with severe stroke in this group had lower 90-day mortality (34.6% vs 62.5%, p = 0.045) and higher rates of good clinical outcome at discharge (33.3% vs 8.3%, p = 0.032). No differences were observed in 90-day haemorrhagic or ischaemic events. CONCLUSION: Continuation of anticoagulation in patients with acute ischaemic stroke and cardioembolic source did not increase the risk of intracranial haemorrhage and may be associated with better functional outcomes.

Impact of post-stroke aphasia on functional communication, quality of life, perception of health and depression: A case-control study.

BACKGROUND AND PURPOSE: Post-stroke aphasia is associated with a reduced quality of life (QoL) and higher risk of depression. Few studies have addressed the effect of coping with aphasia. Our aim is to evaluate the impact of post-stroke aphasia on self-reported QoL and symptoms of depression. METHODS: This was a cross-sectional prospective case-control study. Cases involved patients with post-stroke aphasia included in the DULCINEA trial (NCT04289493). Healthy controls were recruited using snowball sampling. All subjects completed the following questionnaires: General Health Questionnaire (GHQ-12), Stroke Aphasia Quality of Life Scale (SAQOL-39), Communicative Activity Log (CAL) and Stroke Aphasic Depression Questionnaire (SADQ-10). RESULTS: Twenty-three patients (eight women; mean age 62.9 years) and 73 controls (42 women; mean age 53.7 years) were included. Cases scored lower than controls in perception of health (GHQ-12: median 3 [IQR 1; 6] vs. 0 [IQR 0; 2]) and perception of QoL (SAQOL-39: median 3.6 [IQR 3.3; 40] vs. 4.6 [IQR 4.2; 4.8]). Functional communication (CAL: median 135 [IQR 122; 148] vs. 94 [IQR 74; 103]) and SAQOL-39 communication subscale (median 2.7 [IQR 2.1; 3.2] vs. 4.8 [IQR 4.6; 5.0]) were also significantly lower in the case group. Notably, cases reported fewer depressive symptoms than controls (SADQ-10: median 11 [IQR 9; 15] vs. 13 [IQR 11; 16]; p = 0.016). A mediational analysis revealed that the relationship between post-stroke aphasia and depression was not mediated by functional communication. CONCLUSIONS: Although communication difficulties impact the QoL of patients with post-stroke aphasia, such patients report fewer depressive symptoms on the SADQ-10 scale than healthy people, with no differences in scores related to social participation.

Neck CT angiography in acute stroke: An open window for fast detection of COVID-19 lung involvement? Applicability in telemedicine.

BACKGROUND: Chest CT has been proposed as a screening test to rule out SARS-CoV-2 lung infection in acute stroke. Our objectives are to analyze the predictive value of neck CT angiography (CTA) source images compared with conventional chest CT, the interobserver concordance and the reliability of the diagnosis using a mobile app. METHODS: A retrospective observational study that included acute stroke patients admitted to a stroke center. Two raters blinded to the clinical data evaluated and classified the pulmonary findings in chest CT and neck CTA source images according to the COVID-19 Reporting and Data System (CO-RADS). CTA findings were evaluated using a conventional workstation and the JOIN mobile app. Scores of 3-5 were grouped as appearing typical or indeterminate for COVID-19 lung involvement and 0-2 as appearing atypical or negative for pneumonia. SARS-CoV-2 infection was confirmed by polymerase chain reaction (PCR). RESULTS: A total of 242 patients were included (42 with PCR-confirmed COVID-19). In the cohort of 43 patients with both neck CTA and chest CT, the predictive value for COVID-19 was equivalent (sensitivity, 53.8%; specificity, 92.9%). The interobserver agreement in the classification into CO-RADS 3-5 or 1-2 in CTA was good (K = 0.694; standard error, 0.107). In the cohort of 242 patients with neck CTA, the intraobserver agreement between the workstation and the JOIN app was perfect (K = 1.000; standard error 0.000). CONCLUSIONS: Neck CTA enables the accurate identification of COVID-19-associated lung abnormalities in acute stroke. CO-RADS evaluations through mobile applications have a predictive value similar to the usual platforms.

The use of a smartphone application to improve stroke code workflow metrics: A pilot study in a comprehensive stroke centre.

Background: Timely coordination between stroke team members is of relevance for stroke code management. We explore the feasibility and potential utility of a smartphone application for clinical and neuroimaging data sharing for improving workflow metrics of stroke code pathways, and professionals' opinions about its use. Methods: We performed an observational pilot study including stroke code activations at La Paz University Hospital in Madrid, from June 2019 to March 2020. Patients were classified according to the activation or not of the JOIN app by the attending physician. Clinical data and time-to-procedures were retrieved from the app or from the hospital records and the Madrid regional stroke registry as appropriate and compared between both groups. An anonymous survey collected professionals' opinions about the app and its use. Results: A total of 282 stroke code activations were registered. The JOIN app was activated in 111 (39%) cases. They had a significant reduction in imaging-to-thrombolysis (31 vs 20 min, p = .026) and in door-to-thrombolysis times (51 vs 36 min, p = .004), with more patients achieving a door-to-needle time below 45 min (68.8% vs 37.8%, p = .016). About 50% of the users found the app useful for facilitating the diagnosis and decision-making; interoperability with clinical files was considered an opportunity for improvement. Conclusions: This pilot study suggests that JOIN helps improve and document workflow metrics in acute stroke management in a comprehensive stroke centre. These results support testing JOIN in a prospective randomised study to confirm its usefulness and the general applicability of the results.

Final Results of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells in Acute Ischemic Stroke (AMASCIS): A Phase II, Randomized, Double-Blind, Placebo-Controlled, Single-Center, Pilot Clinical Trial.

Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8-20) were randomized (1:1) to receive intravenous adipose tissue-derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3-5.5] vs 7 [0-8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up.

DUbbing Language-therapy CINEma-based in Aphasia post-Stroke (DULCINEA): study protocol for a randomized crossover pilot trial.

BACKGROUND: Communication is one of the most important predictors of social reintegration after stroke. Approximately 15-42% of stroke survivors experience post-stroke aphasia. Helping people recover from aphasia is one of the research priorities after a stroke. Our aim is to develop and validate a new therapy integrating dubbing techniques to improve functional communication. METHODS: The research project is structured as three work packages (WP). WP1: development of the dubbed language cinema-based therapy: Two research assistants (a speech therapist and a dubbing actor) will select the clips, mute specific words/sentences in progressive speech difficulty, and guide patients to dub them across sessions. Words to be dubbed will be those considered to be functionally meaningful by a representative sample of aphasic patients and relatives through an online survey. WP2: a randomized, crossover, interventional pilot study with the inclusion of 54 patients with post-stroke non-fluent aphasia. Patients will be treated individually in 40-min sessions twice per week for 8 weeks. Primary outcomes will be significant pre/post differences in scores in the Communicative Activity Log (CAL) questionnaire and Boston Diagnostic Aphasia Examination (BDAE) administered by a psychologist blinded to the patients' clinical characteristics. SECONDARY OUTCOMES: General Health Questionnaire (GHQ)-12, Stroke Aphasia Quality of Life Scale (SAQOL-39), Western Aphasia Battery Revised (WAB-R), and the Stroke Aphasic Depression Questionnaire (SADQ10). WP3: educational activities and dissemination of results. WP3 includes educational activities to improve public knowledge of aphasia and dissemination of the results, with the participation of the Spanish patients' association Afasia Activa. DISCUSSION: This pilot clinical trial will explore the efficacy of a new therapeutic tool based on dubbing techniques and computer technology to improve functional communication of patients suffering from post-stroke aphasia with the use of standardized test assessment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04289493 . Registered on 28 February 2020.

Concurrent Cerebral, Splenic, and Renal Infarction in a Patient With COVID-19 Infection.

INTRODUCTION: Thrombotic events are potentially devastating complications of coronavirus disease 2019 (COVID-19) infection. Although less common than venous thromboembolism, arterial thrombosis has been reported in COVID-19 cohorts in almost 3% of patients. We describe a patient with COVID-19 infection and concurrent cerebral and noncerebral infarction. CASE REPORT: A 53-year-old man with history of COVID-19 pneumonia was admitted to a primary stroke center for speech disturbances and left hemiplegia. Urgent laboratory tests showed a great increase of inflammatory and coagulation parameters as D-dimer, ferritin, interleukin-6 and C-reactive protein. Neuroimaging found occlusion of the M1 segment of the right middle cerebral artery with early signs of ischemic stroke. He received intravenous thrombolysis and mechanical thrombectomy. Abdominal computed tomography discovered a splenic infarction with hemorrhagic transformation and bilateral renal infarction. Urgent angiography showed an associated splenic pseudoaneurysm, which was embolized without complications. He was treated with intermediate-dose anticoagulation (1 mg subcutaneous enoxaparin/kg/24 h), acetylsalicylic acid 100 mg and 5 days of intravenous corticosteroids. In the following days, inflammatory markers decreased so anticoagulant treatment was stopped and acetylsalicylic acid 300 mg was prescribed. His condition improved and he was discharged to a rehabilitation facility on hospital day 30. CONCLUSION: In this case, a patient with multiple thrombotic events in the acute phase of COVID-19 infection, the delimitation of the inflammatory state through analytical markers as D-dimer helped to individualize the antithrombotic treatment (full anticoagulation or anticoagulation at intermediate doses plus antiplatelet treatment as used in our patient) and its duration. However, more data are needed to better understand the mechanisms and treatment of stroke in patients with COVID-19 infection.

The Role of Ultrasound as a Diagnostic and Therapeutic Tool in Experimental Animal Models of Stroke: A Review.

Ultrasound is a noninvasive technique that provides real-time imaging with excellent resolution, and several studies demonstrated the potential of ultrasound in acute ischemic stroke monitoring. However, only a few studies were performed using animal models, of which many showed ultrasound to be a safe and effective tool also in therapeutic applications. The full potential of ultrasound application in experimental stroke is yet to be explored to further determine the limitations of this technique and to ensure the accuracy of translational research. This review covers the current status of ultrasound applied to monitoring and treatment in experimental animal models of stroke and examines the safety, limitations, and future perspectives.

Fewer COVID-19-associated strokes and reduced severity during the second COVID-19 wave: The Madrid Stroke Network.

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.

Concurrent Stroke and Myocardial Infarction After Mild COVID-19 Infection.

INTRODUCTION: The concurrency of both, acute stroke and acute myocardial infarction in normal conditions, outside the pandemic is rare. Coagulopathy has been associated with the inflammatory phase of coronavirus disease (COVID-19) and might be involved in this concurrency. CASES REPORT: We describe 2 patients with previous mild or no symptoms of COVID-19, admitted for acute stroke with recent/simultaneous myocardial infarction in whom admission polymerase chain reaction was negative but serologic testing diagnosed COVID-19. In these patients, concurrent stroke and myocardial infarction could have been promoted by COVID-19 infection. Management and evolution are detailed, and their contacts to confirm the COVID-19 infection. Pathogenic analysis of possible hypercoagulation state is described suggesting the hypothesis of endothelial dysfunction as the strongest mechanism involved in thrombus formation after the acute phase of COVID-19 infection. CONCLUSIONS: Our experience with these cases suggests that patients with mild symptoms can also present thromboembolic complications once the acute phase of COVID-19 infection has passed.

Usefulness of orbital colour Doppler ultrasound in vascular-related monocular vision loss.

Acute, painless, monocular vision loss (APMVL) usually has a vascular aetiology. We conducted a prospective observational study from 2011 to 2018 to analyse the added value of colour Doppler imaging to assess orbital vessel blood flow in the diagnosis of APMVL. The study included 67 patients (39 [58.2%] men; mean age, 65.9 years [SD 13.7]) with APMVL evaluated at the Neurosonology Laboratory within the first 5 days of symptom onset, who were classified as having either transient or persistent monocular blindness. The blood flow in the ophthalmic and central retinal arteries was assessed using colour Doppler ultrasound with a linear 7.5-MHz transducer. Thirty-three (49.3%) patients presented transient monocular blindness, with reduced blood flow in either the ophthalmic or central retinal artery. The group with persistent vision loss included 24 cases of central retinal artery occlusion (CRAO) and 10 cases of ischaemic optic neuropathy (35.8% and 14.9%, respectively, of the total sample). These patients were older and had a higher prevalence of hypertension and mild carotid atherosclerosis. Orbital colour Doppler ultrasound (OCDUS) clarified the mechanism/cause of the ischaemia in 11 (16.4%) patients and showed abnormal flow in 46 (68.7%) patients, confirming the vascular origin in 19 (57.6%) of the transient monocular blindness cases. Lower peak systolic velocity was observed in patients with CRAO (p < 0.001), and a velocity < 10 cm/s in the central retinal artery was independently associated with the diagnosis of CRAO. OCDUS can be helpful in confirming the vascular cause and identifying the aetiology of APMVL.

Stroke Acute Management and Outcomes During the COVID-19 Outbreak: A Cohort Study From the Madrid Stroke Network.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.

B-Mode Ultrasound, a Reliable Tool for Monitoring Experimental Intracerebral Hemorrhage.

Background: Magnetic resonance imaging (MRI) is currently used for the study of intracerebral hemorrhage (ICH) in animal models. However, ultrasound is an inexpensive, non-invasive and rapid technique that could facilitate the diagnosis and follow-up of ICH. This study aimed to evaluate the feasibility and reliability of B-mode ultrasound as an alternative tool for in vivo monitoring of ICH volume and brain structure displacement in an animal model. Methods: A total of 31 male and female Sprague-Dawley rats were subjected to an ICH model using collagenase-IV in the striatum following stereotaxic references. The animals were randomly allocated into 3 groups: healthy (n = 10), sham (n = 10) and ICH (n = 11). B-mode ultrasound studies with a 13-MHz probe were performed pre-ICH and at 5 h, 48 h, 4 d and 1 mo post-ICH for the assessment of ICH volume and displacement of brain structures, considering the distance between the subarachnoid cisterns and the dura mater. The same variables were studied by MRI at 48 h and 1 mo post-ICH. Results: Both imaging techniques showed excellent correlation in measuring ICH volume at 48 h (r = 0.905) and good at 1 mo (r = 0.656). An excellent correlation was also observed in the measured distance between the subarachnoid cisterns and the dura mater at 1 mo between B-mode ultrasound and MRI, on both the ipsilateral (r = 0.870) and contralateral (r = 0.906) sides of the lesion. Conclusion: B-mode ultrasound imaging appears to be a reliable tool for in vivo assessment of ICH volume and displacement of brain structures in animal models.

Long-Term Anticoagulation in Secondary Ischemic Stroke Prevention: The Prospective Multicenter RESTAIC Registry.

Background and Objective: Oral anticoagulation (OAC) for secondary stroke prevention is recommended in atrial fibrillation (AF) and other sources of cardioembolic stroke. Our objectives were to explore the differences in ischemic and hemorrhagic events when using OAC for secondary stroke prevention according to the type of anticoagulant treatment and to analyze the number and reasons for OAC switches during long-term follow-up. Methods: Ischemic stroke (IS) patients who were discharged on OAC for secondary stroke prevention from January 2014 to October 2017 were recruited in a prospective, multicenter, hospital-based registry. Follow-up at 3 months was scheduled at the outpatient clinic with subsequent annual phone interviews for 3 years. Patients were classified into three study groups according to OAC at discharge: Vitamin K antagonist (VKA), Factor Xa inhibitor (FXa), or direct thrombin inhibitor (DTI). We compared stroke recurrences, intracranial hemorrhage, major bleeding, and all-cause mortality during the follow-up. We recorded any switches in OAC and the main reasons for the change. Results: A total of 241 patients were included. An anticoagulant was indicated in the presence of a source of cardioembolic stroke in 240 patients (99.6%) and lupus plus antiphospholipid syndrome in one patient. Up to 86 patients (35.6%) were on OAC before the index stroke; in 71 (82.5%) of them, this was VKA. At hospital discharge, 105 were treated with FXa (43.8%), 96 with VKA (39.6%), and 40 with DTI (16.6%). The cumulative incidences at 3 years were 17% for stroke recurrence, 1.6% for intracranial hemorrhage, 4.9% for major hemorrhage, and 22.8% for all-cause mortality, with no differences among the OAC groups in any outcomes. During the follow-up, 40 OAC switches were recorded (63% of them to FXa), mostly due to stroke recurrence. Conclusion: Long-term OAC in secondary stroke prevention is associated with a lower frequency of bleeding complications than stroke recurrences. No differences between anticoagulant drugs were found in any of the analyzed outcomes. The main cause for OAC switch during follow-up was stroke recurrence.

Identification of brain structures and blood vessels by conventional ultrasound in rats.

BACKGROUND: Ultrasound is a safe, non-invasive and affordable imaging technique for the visualization of internal structures and the measurement of blood velocity using Doppler imaging. However, despite all these advantages, no study has identified the structures of the rat brain using conventional ultrasound. METHODS: A 13 MHz high frequency transducer was used to identify brain structures in the rat. The enlargement of the transcranial window was performed gradually using the ultrasound directly on the skin of the animal, then against the skull, then through a delimited craniotomy and finally through a complete craniotomy. RESULTS: Our results showed that ultrasound allowed the identification of cerebral ventricles and subarachnoid cisterns, as well as the analysis of real-time monitoring of cerebral blood flow in the main brain arteries of the rat. COMPARISON WITH EXISTING METHODS: Ultrasound is a tool with the potential to identify brain structures and blood vessels. In contrast to MRI, transcranial ultrasound is a fast, non-invasive, well tolerated and low-cost method and can be done at the bedside. CONCLUSION: In the present study, we described an atlas of the main brain structures as well as the main vasculature in the rat using ultrasound. This technique could be applied in animal models of various neurological diseases.

Cell-Based Therapies for Stroke: Promising Solution or Dead End? Mesenchymal Stem Cells and Comorbidities in Preclinical Stroke Research.

Stroke is a major health problem worldwide. It has been estimated that 90% of the population attributable risk of stroke is due to risk factors such as aging, hypertension, hyperglycemia, diabetes mellitus and obesity, among others. However, most animal models of stroke use predominantly healthy and young animals. These models ignore the main comorbidities associated with cerebrovascular disease, which could be one explanation for the unsuccessful bench-to-bedside translation of protective and regenerative strategies by not taking the patient's situation into account. This lack of success makes it important to incorporate comorbidities into animal models of stroke in order to study the effects of the various therapeutic strategies tested. Regarding cell therapy, the administration of stem cells in the acute and chronic phases has been shown to be safe and effective in experimental animal models of stroke. This review aims to show the results of studies with promising new therapeutic strategies such as mesenchymal stem cells, which are being tested in preclinical models of stroke associated with comorbidities and in elderly animals.

Mechanical thrombectomy for basilar artery thrombosis: a comparison of outcomes with anterior circulation occlusions.

BACKGROUND AND PURPOSE: The benefits of mechanical thrombectomy (MT) in basilar artery occlusions (BAO) have not been explored in recent clinical trials. We compared outcomes and procedural complications of MT in BAO with anterior circulation occlusions. METHODS: Data from the Madrid Stroke Network multicenter prospective registry were analyzed, including baseline characteristics, procedure times, procedural complications, symptomatic intracranial hemorrhage (SICH), modified Rankin Scale (mRS), and mortality at 3 months. RESULTS: Of 479 patients treated with MT, 52 (11%) had BAO. The onset to reperfusion time lapse was longer in patients with BAO (median (IQR) 385 min (320-540) vs 315 min (240-415), p<0.001), as was the duration of the procedures (100 min (40-130) vs 60 min (39-90), p=0.006). Moreover, the recanalization rate was lower (75% vs 84%, p=0.01). A trend toward more procedural complications was observed in patients with BAO (32% vs 21%, p=0.075). The frequency of SICH was 2% vs 5% (p=0.25). At 3 months, patients with BAO had a lower rate of independence (mRS 0-2) (40% vs 58%, p=0.016) and higher mortality (33% vs 12%, p<0.001). The rate of futile recanalization was 50% in BAO versus 35% in anterior circulation occlusions (p=0.05). Age and duration of the procedure were significant predictors of futile recanalization in BAO. CONCLUSIONS: MT is more laborious and shows more procedural complications in BAO than in anterior circulation strokes. The likelihood of futile recanalization is higher in BAO and is associated with greater age and longer procedure duration. A refinement of endovascular procedures for BAO might help optimize the results.

Mechanical thrombectomy in patients with medical contraindications for intravenous thrombolysis: a prospective observational study.

BACKGROUND AND PURPOSE: The present study was conducted with the objective of evaluating the safety of primary mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke and comorbidities that preclude treatment with IV thrombolysis (IVT), compared with patients who received standard IVT treatment followed by MT. Secondary objectives were to analyse the recanalization rate and outcomes. METHODS: A prospective observational multicenter study (FUN-TPA) that recruited patients treated within 4.5 hours of symptom onset was performed. Treatments were IVT followed by MT if occlusion persisted, or primary MT when IVT was contraindicated. Outcome measures were procedural complications, symptomatic intracranial hemorrhage (SICH), recanalization rate, National Institutes of Health Stroke Scale (NIHSS) score at 7 days, modified Rankin Scale (mRS) score and mortality at 90 days. RESULTS: Of 131 patients, 21 (16%) had medical contraindications for IVT and were treated primarily with MT whereas 110 (84%) underwent IVT, followed by MT in 53 cases (40%). The recanalization rate and procedural complications were similar in the two groups. There were no SICHs after primary MT vs 3 (6%) after IVT+MT. Nine patients (43%) in the primary MT group achieved independence (mRS 0-2) compared with 36 (68%) in the IVT+MT group (p=0.046). Mortality rates in the two groups were 14% (n=3) vs 4% (n=2) (p=0.13). Adjusted ORs for independence in patients receiving standard IVT+MT vs MT in patients with medical contraindications for IVT were 2.8 (95% CI 0.99 to 7.98) and 0.24 (95% CI 0.04 to 1.52) for mortality. CONCLUSIONS: MT is safe in patients with potential comorbidity-derived risks that preclude IVT. MT should be offered, aiming for prompt recanalization, to patients with LVO stroke unsuitable for IVT. TRIAL REGISTRATION NUMBER: NCT02164357; Results.