EnDovascular Therapy Plus Best Medical Treatment (BMT) Versus BMT Alone for MedIum distal VeSsel Occlusion sTroke (DISTAL): An international, multicentre, randomized-controlled, two-arm, assessor-blinded trial.

RATIONALE: Whether endovascular therapy (EVT) in addition to best medical treatment (BMT) in people with acute ischemic stroke (AIS) due to a medium distal vessel occlusion (MDVO) is beneficial remains unclear. AIM: To determine if people experiencing an AIS due to an isolated MDVO (defined as the co- or non-dominant M2 segment, the M3 or M4 segment of the middle cerebral artery, the A1, A2, or A3 segment of the anterior cerebral artery or the P1, P2 or P3 segment of the posterior cerebral artery) will have superior outcome if treated with EVT in addition to BMT compared to BMT alone. SAMPLE SIZE: To randomize 526 participants 1:1 to EVT plus BMT or BMT alone. METHODS AND DESIGN: A multicentre, international, prospective, randomized, open-label, blinded-endpoint (PROBE) superiority trial. OUTCOMES: The primary efficacy endpoint is the distribution of disability levels on the modified Rankin Scale at 90 days. Secondary clinical efficacy outcomes include normalized change in National Institutes of Health Stroke Scale score from baseline to day 1, cognitive outcome at 90 days, and health-related quality of life at 90 days. Safety outcomes include all serious adverse events, symptomatic intracranial hemorrhage within 24 h, and all-cause mortality up to 90 days. Secondary imaging outcomes include successful reperfusion at end of EVT procedure and recanalization of target artery at 24 h. DISCUSSION: DISTAL will inform physicians whether EVT in addition to BMT in people with AIS due to a MDVO is more efficacious than BMT alone.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and signs of neurodegeneration: a prospective cross-sectional study

ImportanceGrowing evidence suggests that coronavirus disease 2019 (COVID-19) is associated with neurological sequelae. However, the underlying pathophysiological mechanisms resulting in central nervous system (CNS) derogation remain unclear. ObjectiveTo identify severity-dependent immune mechanisms in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients and their association with brain imaging alterations. DesignProspective cross-sectional cohort study. SettingThis study was performed from August 2020 to April 2021. Participants were enrolled in the outpatient clinics, hospital wards and intensive care units (ICU) of two clinical sites in Basel and Zurich, Switzerland. ParticipantsAge >18 years and a positive SARS-CoV-2 test result were inclusion criteria. Potentially matching individuals were identified (n=310), of which 269 declined to participate and 1 did not match inclusion criteria. Paired CSF and plasma samples, as well as brain images, were acquired. The COVID-19 cohort (n=40; mean [SD] age, 54 [20] years; 17 women (42%)) was prospectively assorted by neurological symptom severity (classes I, II and III). Age/sex-matched inflammatory (n=25) and healthy (n=25) CSF and plasma control samples were obtained. For volumetric brain analysis, a healthy age/sex-matched control cohort (n=36) was established. ExposuresLumbar puncture, blood sampling and cranial MRI and/or CT. Main outcomes and measuresProteomics, standard parameters and antibody profiling of paired CSF and plasma samples in COVID-19 patients and controls. Brain imaging and gray matter volumetric analysis in association with biomarker profiles. Follow-up after 10-months. ResultsCOVID-19 patients displayed a plasma cytokine storm but a non-inflammatory CSF profile. Class III patients displayed signs of blood-brain barrier (BBB) impairment and a polyclonal B cell response targeting self- and non-self antigens. Decreased regional brain volumes were present in COVID-19 patients and associated with specific CSF and plasma parameters. Conclusion and relevanceNeuro-COVID class III patients had a strong, peripheral immune response resulting in (1) BBB impairment (2) ingress of (auto-)antibodies, (3) microglia activation and neuronal damage signatures. Our data point towards several potentially actionable targets that may be addressed to prevent COVID-19-related neurological sequelae. Trial registrationThe trial (NCT04472013) was registered on clinicaltrials.gov. Key pointsO_ST_ABSQuestionC_ST_ABSDoes a severity-dependent pattern of immune mechanisms exist in the cerebrospinal fluid (CSF) and plasma of COVID-19 patients and are these associated with clinical and brain imaging findings? FindingsNeuro-COVID patients display a robust class III-specific peripheral immune response resulting in (1) blood-brain barrier (BBB) impairment, (2) ingress of (auto-)antibodies, (3) microglia activation and neuronal damage signatures. Integration of MRIs, brain volumetry and proteomics identified biomarkers associated with regional brain volume loss in severe Neuro-COVID. MeaningWe provide a multidimensional framework of mechanisms associated with severe Neuro-COVID and present possible targets to prevent COVID-19-related neurological sequelae.

Brain cortical changes are related to inflammatory biomarkers in hospitalized SARS-CoV-2 patients with neurological symptoms

Increasing evidence shows that the brain is a target of SARS-CoV-2. However, the consequences of the virus on the cortical regions of hospitalized patients are currently unknown. The purpose of this study was to assess brain cortical gray matter volume (GMV), thickness (Th), and surface area (SA) characteristics in SARS-CoV-2 hospitalized patients with a wide range of neurological symptoms and their association with clinical indicators of inflammatory processes. A total of 33 patients were selected from a prospective, multicenter, cross-sectional study during the ongoing pandemic (August 2020-April 2021) at Basel University Hospital. Retrospectively biobank healthy controls with the same image protocol served as controls group. For each anatomical T1w MPRAGE image, the Th and GMV segmentation were performed with the FreeSurfer-5.0. Cortical measures were compared between groups using a linear regression model. The covariates were age, gender, age*gender, MRI magnetic field strength, and total intracranial volume/mean Th/Total SA. The association between cortical features and laboratory variables was assessed using partial correlation adjusting for the same covariates. P-values were adjusted using false discovery rate (FDR). Our findings revealed a lower cortical gray matter volume in orbitofrontal and cingulate regions in patients compared to controls. The orbitofrontal grey matter volume was negatively associated with protein levels, CSF-blood/albumin ratio and CSF EN-RAGE level. CSF EN-RAGE and CSF/Blood-albumin ratio, which are neuroinflammatory biomarkers, were associated with cortical alterations in gray matter volume and thickness in frontal, orbitofrontal, and temporal regions. Our data suggest that viral-triggered inflammation leads to increased neurotoxic damage in some cortical areas.

SMART coils for intracranial aneurysm repair - a single center experience.

BACKGROUND: Due to uniform stiffness of standard platinum coils, dense packing of intracranial aneurysms can be difficult to achieve, since stiffer coils can cause microcatheter prolapse or coil migration. SMART coils have a varying softness along the length of the coils to improve deliverability. We report our initial 2 year experience with the SMART coil system, including direct and follow-up results. METHODS: We performed a retrospective study of all patients who underwent coil embolization of an intracranial aneurysm with SMART coils between July 2016 and August 2018 at our institution. We analyzed clinical and angiographic data before and directly after treatment as well as at 6 months follow-up. RESULTS: A total of 49 patients harboring 49 aneurysms were treated; 23 (47%) were ruptured aneurysms. Most aneurysms (57%) were located in the anterior circulation. Median patient age was 55 (31-88), 63% were female. Mean aneurysm size was: neck 3.4 (±1.5), height 6.3 (±2.9) and width 5.2 (±2.3) mm. SMART coils were solely used in 96% of cases. Initial favorable angiographic results were achieved in 45 (92%) of 49 cases, which were stable at 6 months in 26/29 (90%). Thromboembolic complications occurred in 4 (8%) cases without clinical sequelae; microcatheter prolapse occurred in 1 case. No aneurysm rupture or device malfunction was observed. CONCLUSION: The treatment of ruptured and unruptured intracranial aneurysms with SMART Coils was safe and efficacious in our cohort.

Alternative Transcarotid Approach for Endovascular Treatment of Acute Ischemic Stroke Patients: A Case Series / 신경중재치료의학

PURPOSE: Mechanical thrombectomy has become the standard of care for acute stroke caused by large vessel occlusion. As more patients are treated endovascularly, the number of older patients with tortuous vessels has risen. In these patients, catheterizing the internal carotid artery via a transfemoral approach can be very difficult or even impossible. Therefore, in selected patients, alternative strategies to the transfemoral approach have to be applied. MATERIALS AND METHODS: We report a case series of six patients undergoing mechanical thrombectomy via a combined transfemoral and transcarotid approach. Puncture of the carotid artery was conducted using roadmap guidance after an unsuccessful transfemoral attempt. Technical aspects and outcomes with this alternative approach were analyzed. RESULTS: Direct puncture of the carotid artery was achieved in five out of six patients (83%). In three out of six patients (50%), revascularization (modified Thrombolysis in Cerebral Infarction score ≥2b) was restored. No complications related to endovascular therapy were documented. One patient showed good neurological outcome (modified Rankin Scale [mRS] 5 at admission, mRS 1 at discharge). CONCLUSION: A combined transfemoral/transcarotid approach can be an alternative vascular access in patients with problematic vessel anatomy.

Outcome Prediction Using Perfusion Parameters and Collateral Scores of Multi-Phase and Single-Phase CT Angiography in Acute Stroke: Need for One, Two, Three, or Thirty Scans? / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Collateral status is an important factor determining outcome in acute ischemic stroke (AIS). Hence, different collateral scoring systems have been introduced. We applied different scoring systems on single- and multi-phase computed tomography (CT) angiography (spCTA and mpCTA) and compared them to CT perfusion (CTP) parameters to identify the best method for collateral evaluation in patients with AIS. METHODS: A total of 102 patients with AIS due to large vessel occlusion in the anterior circulation who underwent multimodal CT imaging and who were treated endovascularly were included. Collateral status was assessed on spCTA and mpCTA using four different scoring systems and compared to CTP parameters. Logistic regression was performed for predicting favorable outcome. RESULTS: All collateral scores correlated well with each other and with CTP parameters. Comparison of collateral scores stratified by extent of perfusion deficit showed relevant differences between groups (P < 0.01 for each). An spCTA collateral score discriminated best between favorable and unfavorable outcome as determined using the modified Rankin Scale 3 months after stroke. CONCLUSIONS: Collateral status evaluated on spCTA may suffice for outcome prediction and decision making in AIS patients, potentially obviating further imaging modalities like mpCTA or CTP.