Excellent response to anti-CD38 therapy with daratumumab in a patient with severe refractory CANOMAD.

BACKGROUND: Intravenous immunoglobulin (IVIG) and rituximab are considered the first-line and second-line treatments for Chronic Ataxic Neuropathy and Ophthalmoplegia with IgM-paraprotein, cold Agglutinins, and anti-Disialosyl antibodies (CANOMAD), with an overall clinical response around 50%. New anti-CD38 daratumumab, targeting long-lived plasma cells, has been reported as a promising therapy for treatment-refractory antibody-mediated disorders. We report the first case of a severe refractory CANOMAD, successfully treated with daratumumab. METHODS: A patient in their 70s with severe relapsing CANOMAD, refractory to IVIG, steroids, rituximab and ibrutinib developed severe tetraparesis and respiratory failure. Plasma exchange (PE) improved motor and ventilatory function; however, after 6 weeks, patient remained PE dependent. Intravenous daratumumab was initiated at 16 mg/kg weekly for 3 weeks, every 2 weeks for the second and third month, and monthly afterwards. RESULTS: After 3 weeks of starting daratumumab, PE was discontinued and, since then, the patient evolved to complete recovery. Antidisialosyl antibody titres decreased after PE and remained stable during daratumumab. Serum neurofilament light-chain levels were elevated in the exacerbation phase and normalised after daratumumab. The patient remains in clinical remission under monthly daratumumab, 12 months after initiation. CONCLUSIONS: The first patient with aggressive treatment-refractory CANOMAD treated with daratumumab provides proof-of-principle evidence that daratumumab may be an effective treatment in IgM-related neuropathies.

Radiological pattern in cryptogenic stroke/TIA patients with and without thrombophilia.

BACKGROUND: The radiological pattern of stroke patients with thrombophilia is unknown. Our aim is to compare the MRI radiological pattern of silent and acute lesions in cryptogenic stroke/TIA patients under 60 years of age with and without thrombophilia. METHODS: Cryptogenic stroke/TIA patients under 60 years of age hospitalized at our Stroke Unit during four years were consecutively included. Thrombophilia screening was performed at 3 months after stroke and verified 12 weeks later. The follow-up was performed at 3, 12 and 24 months. Radiological pattern was assessed with the Fazekas and van Swieten scales. RESULTS: During four years, 185 cryptogenic stroke/TIA patients under 60 years of age were included; mean age was 51 years, 61% were female, with a follow-up of 22±3.2 months. Thrombophilia was detected in 20% of patients. We detected a significant increase of previous vascular events (29.7% vs 7.5%, p=.01) as well as lower hypercholesterolemia (27% vs 62.5% p=.003) in the thrombophilia group, without significant differences in other vascular risk factors or vascular recurrence during follow-up. Regarding the acute lesion, we did not detect significant differences between groups. The radiological pattern of silent lesions showed that the thrombophilia group presented more large confluent lesions (39.1% vs 19.2%, p=.02) with greater sparing of the anterior territory (0% vs 30%, p=.01). CONCLUSIONS: Our data suggest a characteristic radiological pattern of silent lesions in cryptogenic stroke/TIA patients with thrombophilia, with more confluent lesions and less involvement of the anterior territory.

Association of Time of Day With Outcomes Among Patients Triaged for a Suspected Severe Stroke in Nonurban Catalonia.

BACKGROUND: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. METHODS: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. RESULTS: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR], 1.620 [95% CI, 1.020-2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680-1.163]; P interaction=0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548-1.072]; nighttime, acOR, 1.785 [95% CI, 1.024-3.112] ; P interaction<0.01); no heterogeneity was observed for other stroke subtypes (P interaction>0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. CONCLUSIONS: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795962.

Determinants and Trends of the Use of Intravenous Thrombolysis for Minor Stroke: A Population-Based Study, 2016 to 2020.

BACKGROUND: We analyzed the main factors associated with intravenous thrombolysis (IVT) in patients with minor ischemic stroke. METHODS: Data were obtained from a prospective, government-mandated, population-based registry of stroke code patients in Catalonia (6 Comprehensive Stroke Centers, 8 Primary Stroke Centers, and 14 TeleStroke Centers). We selected patients diagnosed with ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) ≤5 at hospital admission from January 2016 to December 2020. We excluded patients with a baseline modified Rankin Scale score of ≥3, absolute contraindication for IVT, unknown stroke onset, or admitted to hospital beyond 4.5 after stroke onset. The main outcome was treatment with IVT. We performed univariable and binary logistic regression analyses to identify the most important factors associated with IVT. RESULTS: We included 2975 code strokes; 1433 (48.2%) received IVT of which 30 (2.1%) had a symptomatic hemorrhagic transformation. Patients treated with IVT as compared to patients who did not receive IVT were more frequently women, had higher NIHSS, arrived earlier to hospital, were admitted to a Comprehensive Stroke Centers, and had large vessel occlusion. After binary logistic regression, NIHSS score 4 to 5 (odds ratio, 40.62 [95% CI, 31.73-57.22]; P<0.001) and large vessel occlusion (odds ratio, 16.39 [95% CI, 7.25-37.04]; P<0.001) were the strongest predictors of IVT. Younger age, female sex, baseline modified Rankin Scale score of 0, earlier arrival to hospital (<120 minutes after stroke onset), and the type of stroke center were also independently associated with IVT. The weight of large vessel occlusion on IVT was higher in patients with lower NIHSS. CONCLUSIONS: Minor stroke female patients, with higher NIHSS, arriving earlier to the hospital, presenting with large vessel occlusion and admitted to a Comprehensive Stroke Centers were more likely to receive intravenous thrombolysis.

Effect of Direct Transportation to Thrombectomy-Capable Center vs Local Stroke Center on Neurological Outcomes in Patients With Suspected Large-Vessel Occlusion Stroke in Nonurban Areas: The RACECAT Randomized Clinical Trial.

Importance: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective: To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants: Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions: Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures: The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death]) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results: Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21]); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance: In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration: ClinicalTrials.gov Identifier: NCT02795962.

The Role of Vascular Imaging atReferral Centers in the Drip and Ship Paradigm.

BACKGROUND: In drip-and-ship protocols, non-invasive vascular imaging (NIVI) at Referral Centers (RC), although recommended, is not consistently performed and its value is uncertain. We evaluated the role of NIVI at RC, comparing patients with (VI+) and without (VI-) vascular imaging in several outcomes. METHODS: Observational, multicenter study from a prospective government-mandated population-based registry of code stroke patients. We selected acute ischemic stroke patients, initially assessed at RC from January-2016 to June-2020. We compared and analyzed the rates of patients transferred to a Comprehensive Stroke Center (CSC) for Endovascular Treatment (EVT), rates of EVT and workflow times between VI+ and VI- patients. RESULTS: From 5128 ischemic code stroke patients admitted at RC; 3067 (59.8%) were VI+, 1822 (35.5%) were secondarily transferred to a CSC and 600 (11.7%) received EVT. Among all patients with severe stroke (NIHSS ≥16) at RC, a multivariate analysis showed that lower age, thrombolytic treatment, and VI+ (OR:1.479, CI95%: 1.117-1.960, p=0.006) were independent factors associated to EVT. The rate of secondary transfer to a CSC was lower in VI+ group (24.6% vs. 51.6%, p<0.001). Among transferred patients, EVT was more frequent in VI+ than VI- (48.6% vs. 21.7%, p<0.001). Interval times as door-in door-out (median-minutes 83.5 vs. 82, p= 0.13) and RC-Door to puncture (median-minutes 189 vs. 178, p= 0.47) did not show differences between both groups. CONCLUSION: In the present study, NIVI at RC improves selection for EVT, and is associated with receiving EVT in severe stroke patients. Time-metrics related to drip-and-ship model were not affected by NIVI.

Impact of COVID-19 Infection on the Outcome of Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: We evaluated whether stroke severity, functional outcome, and mortality are different in patients with ischemic stroke with or without coronavirus disease 2019 (COVID-19) infection. METHODS: A prospective, observational, multicentre cohort study in Catalonia, Spain. Recruitment was consecutive from mid-March to mid-May 2020. Patients had an acute ischemic stroke within 48 hours and a previous modified Rankin Scale (mRS) score of 0 to 3. We collected demographic data, vascular risk factors, prior mRS score, National Institutes of Health Stroke Scale score, rate of reperfusion therapies, logistics, and metrics. Primary end point was functional outcome at 3 months. Favourable outcome was defined depending on the previous mRS score. Secondary outcome was mortality at 3 months. We performed mRS shift and multivariable analyses. RESULTS: We evaluated 701 patients (mean age 72.3±13.3 years, 60.5% men) and 91 (13%) had COVID-19 infection. Median baseline National Institutes of Health Stroke Scale score was higher in patients with COVID-19 compared with patients without COVID-19 (8 [3-18] versus 6 [2-14], P=0.049). Proportion of patients with a favourable functional outcome was 33.7% in the COVID-19 and 47% in the non-COVID-19 group. However, after a multivariable logistic regression analysis, COVID-19 infection did not increase the probability of unfavourable functional outcome. Mortality rate was 39.3% among patients with COVID-19 and 16.1% in the non-COVID-19 group. In the multivariable logistic regression analysis, COVID-19 infection was a risk factor for mortality (hazard ratio, 3.14 [95% CI, 2.10-4.71]; P<0.001). CONCLUSIONS: Patients with ischemic stroke and COVID-19 infection have more severe strokes and a higher mortality than patients with stroke without COVID-19 infection. However, functional outcome is comparable in both groups.

Bottlenecks in the Acute Stroke Care System during the COVID-19 Pandemic in Catalonia.

INTRODUCTION: The COVID-19 pandemic resulted in significant healthcare reorganizations, potentially striking standard medical care. We investigated the impact of the COVID-19 pandemic on acute stroke care quality and clinical outcomes to detect healthcare system's bottlenecks from a territorial point of view. METHODS: Crossed-data analysis between a prospective nation-based mandatory registry of acute stroke, Emergency Medical System (EMS) records, and daily incidence of COVID-19 in Catalonia (Spain). We included all stroke code activations during the pandemic (March 15-May 2, 2020) and an immediate prepandemic period (January 26-March 14, 2020). Primary outcomes were stroke code activations and reperfusion therapies in both periods. Secondary outcomes included clinical characteristics, workflow metrics, differences across types of stroke centers, correlation analysis between weekly EMS alerts, COVID-19 cases, and workflow metrics, and impact on mortality and clinical outcome at 90 days. RESULTS: Stroke code activations decreased by 22% and reperfusion therapies dropped by 29% during the pandemic period, with no differences in age, stroke severity, or large vessel occlusion. Calls to EMS were handled 42 min later, and time from onset to hospital arrival increased by 53 min, with significant correlations between weekly COVID-19 cases and more EMS calls (rho = 0.81), less stroke code activations (rho = -0.37), and longer prehospital delays (rho = 0.25). Telestroke centers were afflicted with higher reductions in stroke code activations, reperfusion treatments, referrals to endovascular centers, and increased delays to thrombolytics. The independent odds of death increased (OR 1.6 [1.05-2.4], p 0.03) and good functional outcome decreased (mRS ≤2 at 90 days: OR 0.6 [0.4-0.9], p 0.015) during the pandemic period. CONCLUSION: During the COVID-19 pandemic, Catalonia's stroke system's weakest points were the delay to EMS alert and a decline of stroke code activations, reperfusion treatments, and interhospital transfers, mostly at local centers. Patients suffering an acute stroke during the pandemic period had higher odds of poor functional outcome and death. The complete stroke care system's analysis is crucial to allocate resources appropriately.

Vascular Occlusion Evolution in Endovascular Reperfusion Candidates Transferred from Primary to Comprehensive Stroke Centers.

BACKGROUND: The evolution of the symptomatic intracranial occlusion during transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) for endovascular treatment (EVT) is not widely known. Our aim was to identify factors related to partial or complete recanalization (REC) at CSC arrival in patients with a documented large vessel occlusion (LVO) in PSC transferred for EVT evaluation to better define the workflow at CSC of this group of patients. METHODS: We conducted an observational, multicenter study from a prospective, government-mandated, population-based registry of stroke patients with documented LVO at PSC transferred to CSC for EVT from January 2017 to June 2019. The primary end point was defined as partial or complete REC that precluded EVT at CSC arrival (REC). We evaluated the association between baseline, treatment variables and time intervals with the presence of REC. RESULTS: From 589 patients, the rate of REC at CSC was 10.5% in all LVO patients transferred from PSC to CSC for EVT evaluation. On univariate analysis, lower PSC-NIHSS (median 12vs.16, p = 0.001), tPA treatment at PSC (13.7 vs. 5.0%; p = 0.001), presence of M2 occlusion on PSC (16.8 vs. 9%; p = 0.023), and clinical improvement at CSC arrival (21.7 vs. 9.6% p = 0.001) were associated with REC at CSC. On multivariate analysis, clinical improvement at CSC arrival (p < 0.001, OR: 5.96 95% CI: 2.5-13.9) and PSC tPA treatment predicted REC (p = 0.003, OR: 4.65, 95% CI: 1.73-12.4). CONCLUSION: REC at CSC arrival occurs exceptionally in patients with a documented LVO on PSC. Repeating a second vascular study before EVT would not be necessary in most patients. Despite its modest effect, tPA treatment at PSC was an independent predictor of REC.

Telestroke in Catalonia: Increasing Thrombolysis Rate and Avoiding Interhospital Transfers.

OBJECTIVES: The study aimed to evaluate the impact of a telestroke network on acute stroke care in Catalonia, by measuring thrombolysis rates, access to endovascular treatment, and clinical outcome of telestroke patients in a population-based study. METHODS: Telestroke network was implemented on March 2013 and consists of 12 community hospitals and 1 expert stroke neurologist 24 h/7 day, covering a population of 1.3 million inhabitants. Rest of the population (6.2 million) of Catalonia is covered by 8 primary stroke centers (PSC) and 6 comprehensive stroke centers (CSC). After a 2-way videoconference and visualization of neuroimaging on a web platform, the stroke neurologist decides the therapeutic approach and/or to transfer the patient to another facility, entering these data in a mandatory registry. Simultaneously, all patients treated with reperfusion therapies in all centers of Catalonia are prospectively recorded in a mandatory and audited registry. RESULTS: From March 2013 to December 2015, 1,206 patients were assessed by telestroke videoconference, of whom 322 received intravenous thrombolysis (IVT; 33.8% of ischemic strokes). Baseline and 24 h NIHSS, rate of symptomatic hemorrhage, mortality, and good outcome at 3 months were similar compared to those who received IVT in PSC or CSC (2,897 patients in the same period). The door-to-needle time was longer in patients treated through telestroke, but was progressively reduced from 2013 to 2015. Percentage of patients receiving thrombectomy after IVT was similar in patients treated through telestroke circuit, compared to those treated in PSC or CSC (conventional circuit). Population rates of IVT*100,000 inhabitants in Catalonia increased from 2011 to 2015, especially in areas affected by the implementation of telestroke network, achieving rates as high as 16 per 100,000 inhabitants. Transfers to another facility were avoided after telestroke consultation in 46.8% of ischemic, 76.5% of transient ischemic attacks, and 23.5% of hemorrhages. CONCLUSIONS: Telestroke favors safe and effective thrombolysis, helps to increase the population rate of IVT, and avoids a large number of interhospital transfers.

Clinical Outcome of Ischemic Stroke in Old Patients Versus Oldest-Old.

BACKGROUND: It is unclear whether very old patients benefit from stroke unit. The aim of our work was to compare the clinical outcome of patients with ischemic stroke aged either 70 or 80 (G 1) versus oldest-old greater than or equal to 81 years (G 2). METHODS: Of 1187 patients admitted with stroke during 5 years in our stroke unit, we included 252 patients with independent functional status (modified Rankin scale, [mRS] ≤ 2) before the stroke. All patients underwent clinical examination, blood test, electrocardiography, brain imaging, and cerebrovascular ultrasound. Clinical outcome was assessed with the mRS and National Institutes of Health Stroke Scale (NIHSS) at discharge. We considered favorable outcome mRS 0-2 at discharge. RESULTS: Of 252 patients included, 55% were male, 150 (59.5%) patients belonged to G1 and 102 (40.5%) G2. We detected a significant increase of atrial fibrillation, bronchoaspiration, mortality, higher NIHSS at admission, and worse functional status at discharge in G2. No significant differences in other demographic, vascular risk factors, hospital stay, NIHSS at discharge or subtype of stroke were found. NIHSS at discharge was the only independent predictor of good functional status (odds ratio 0.4; 95% confidence interval, 0.3-0.6; P < .001). CONCLUSIONS: Oldest-old patients showed similar NIHSS at discharge than younger patients despite having higher neurological severity at admission. Our results support the hypothesis that oldest-old patients have good recovery potential, and should not be excluded from the stroke unit. The worse functional status detected at discharge in these patients could be attributed to others factors and not to neurological severity.

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10-03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10-09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03). CONCLUSIONS: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.

Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results From a Multicenter Study.

BACKGROUND AND PURPOSE: Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator. METHODS: This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses. RESULTS: We evaluated 992 patients (mean age, 74.0±12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3-27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6-14.1) increased the risk of rPH. CONCLUSIONS: The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions.

Predictors of occult cancer in acute ischemic stroke patients.

BACKGROUND: We investigated the prevalence of occult malignancy (OM) in acute ischemic stroke patients to evaluate if any biological marker could help to detect the presence of OM. METHODS: We retrospectively reviewed all ischemic stroke patients during 48 months. We did not perform any screening for OM. Demographic data, vascular risk factors, routine blood chemistry with fibrinogen and C-reactive protein (CRP), National Institutes of Health Stroke Scale (NIHSS), and etiological subtype of stroke according to Trial of Org 10172 in Acute Stroke Treatment criteria were analyzed. The patients were divided into 2 groups (Non-OM versus OM). RESULTS: We analyzed 631 patients with acute ischemic stroke. The mean age was 69.7 ± 12.7 years, and 59% were men. The distribution of vascular risk factors, etiological subgroups, and NIHSS was comparable between both groups. We detected 13 cases (2.1%) with OM, and this percentage was higher in patients with stroke of undetermined etiology (5.3%). We detected significant higher levels of fibrinogen and CRP in patients with stroke of undetermined cause with OM. Receiver operating characteristic curves showed a sensitivity of 75% and specificity of 96% for levels of CRP more than 20 mg/L, and a sensitivity of 67% and specificity of 91% for fibrinogen levels greater than 600 mg/dL. CONCLUSIONS: OM was present in 2.1 % of overall patients, and 5.3% of patients with stroke of undetermined cause. Baseline levels of fibrinogen more than 600 mg/dL or CRP greater than 20 mg/L in patients with undetermined stroke might be good predictors of OM.

Functional outcome after primary endovascular therapy or IV thrombolysis alone for stroke. An observational, comparative effectiveness study.

BACKGROUND: Among the acute ischemic stroke patients with large vessel occlusions and contraindications for the use of IV thrombolysis, mainly on oral anticoagulation or presenting too late, primary endovascular therapy is often performed as an alternative to the standard therapy even though evidence supporting the use of endovascular reperfusion therapies is not yet established. Using different statistical approaches, we compared the functional independence rates at 3 months among patients undergoing primary endovascular therapy and patients treated only with IV thrombolysis. METHODS: We used data from a prospective, government-mandated and externally audited registry of reperfusion therapies for ischemic stroke (January 2011 to November 2012). Patients were selected if treated with either IV thrombolysis alone (n = 1,582) or primary endovascular thrombectomy (n = 250). A series of exclusions were made to homogenize the clinical characteristics among the two groups. We then carried out multivariate logistic regression and propensity score matching analyses on the final study sample (n = 1,179) to compare functional independence at 3 months, as measured by the modified Rankin scale scores 0-2, between the two groups. RESULTS: The unadjusted likelihood of good outcome was poorer among the endovascular group (OR: 0.69; 95% CI: 0.47-1.0). After adjustment, no differences by treatment modality were seen (OR: 1.51; 95% CI: 0.93-2.43 for primary endovascular therapy). Patients undergoing endovascular thrombectomy within 180-270 min (OR: 2.89; 95% CI: 1.17-7.15) and patients with severe strokes (OR: 1.84; 95% CI: 1.02-3.35) did better than their intravenous thrombolysis counterparts. The propensity score-matched analyses with and without adjustment by additional covariates showed that endovascular thrombectomy was as effective as intravenous thrombolysis alone in achieving functional independence (OR for unadjusted propensity score matched: 1.35; 95% CI: 0.9-2.02, OR for adjusted propensity score matched: 1.45; 95% CI: 0.91-2.32). CONCLUSION: This comparative effectiveness study shows that in ischemic stroke patients with contraindications for IV thrombolysis, primary endovascular treatment might be an alternative therapy at least as effective as IV thrombolysis alone. Randomized controlled trials are urgently needed.

Analysis of peptidome profiling of serum from patients with early onset symptoms of ischemic stroke.

BACKGROUND: We sought to identify new serum biomarkers for the early diagnosis of ischemic stroke. METHODS: We collected 63 serum samples from patients with neurologic disease (45 patients with ischemic stroke, 18 patients with other neurologic disorders, and 56 healthy controls). Serum peptides were extracted using immobilized copper ion chromatography on a robotic platform. Mass spectra were acquired by matrix-assisted laser desorption/ionization-time of flight mass spectrometry using an Autoflex II spectrometer (Bruker Daltonics, Billerica, MA). Statistical analyses were performed with Clinprotools 2.2 software (Bruker Daltonics) and SPSS software (version 15.0; SPSS, Inc., Chicago, IL). RESULTS: No peptide biomarker or panel of peptide biomarkers was identified to differentiate between ischemic stroke and other neurologic disease, but ischemic stroke patients were differentiated from healthy controls with a single feature of the peptidome (sensitivity 88.6%; specificity 96.4%). CONCLUSIONS: Analysis of peptidome profiling of serum could be a useful tool in the search for early diagnostic biomarkers of ischemic stroke.

Influence of vascular imaging acquisition at local stroke centers on workflows in the drip-n-ship model: a RACECAT post hoc analysis.

BACKGROUND: The influence of vascular imaging acquisition on workflows at local stroke centers (LSCs) not capable of performing thrombectomy in patients with a suspected large vessel occlusion (LVO) stroke remains uncertain. We analyzed the impact of performing vascular imaging (VI+) or not (VI- at LSC arrival on variables related to workflows using data from the RACECAT Trial. OBJECTIVE: To compare workflows at the LSC among patients enrolled in the RACECAT Trial with or without VI acquisition. METHODS: We included patients with a diagnosis of ischemic stroke who were enrolled in the RACECAT Trial, a cluster-randomized trial that compared drip-n-ship versus mothership triage paradigms in patients with suspected acute LVO stroke allocated at the LSC. Outcome measures included time metrics related to workflows and the rate of interhospital transfers and thrombectomy among transferred patients. RESULTS: Among 467 patients allocated to a LSC, vascular imaging was acquired in 277 patients (59%), of whom 198 (71%) had a LVO. As compared with patients without vascular imaging, patients in the VI+ group were transferred less frequently as thrombectomy candidates to a thrombectomy-capable center (58% vs 74%, P=0.004), without significant differences in door-indoor-out time at the LSC (median minutes, VI+ 78 (IQR 69-96) vs VI- 76 (IQR 59-98), P=0.6). Among transferred patients, the VI+ group had higher rate of thrombectomy (69% vs 55%, P=0.016) and shorter door to puncture time (median minutes, VI+ 41 (IQR 26-53) vs VI- 54 (IQR 40-70), P<0.001). CONCLUSION: Among patients with a suspected LVO stroke initially evaluated at a LSC, vascular imaging acquisition might improve workflow times at thrombectomy-capable centers and reduce the rate of futile interhospital transfers. These results deserve further evaluation and should be replicated in other settings and geographies.

Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC. METHODS: This is a multicenter prospective observational and population-based study of a cohort of consecutively recruited patients with ICH (March 2020-March 2022). We included all patients with spontaneous ICH in Catalonia (Spain) who had a pre-ICH modified Rankin scale (mRS) score of 0-3 and who were admitted to the hospital within 24 hours of onset. We compared patients admitted to a TSC/PSC (n = 641) or a CSC (n = 1,320) and also analyzed the subgroup of patients transferred (n = 331) or not transferred (n = 310) from a TSC/PSC to a CSC. The main outcome was the 3-month mRS score obtained by blinded investigators. Outcomes were compared using adjusted ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI for a shift in mRS scores. A propensity score matching (PSM) analysis was performed for the subgroup of transferred patients. RESULTS: Relevant data were obtained from 1961 of a total of 2,230 patients, with the mean (SD) age of 70 (14.1) years, and 713 (38%) patients were women. After adjusting for confounders (age, NIH Stroke Scale score, intraventricular hemorrhage, hematoma volume, and pre-ICH mRS score), type of hospital of initial admission (CSC vs TSC/PSC) was not associated with outcome (adjusted common OR 1.13, 95% CI 0.93-1.38). A PSM analysis indicated that transfer to a CSC was not associated with more favorable outcomes (OR 0.77, 95% CI 0.55-1.10; p = 0.16). DISCUSSION: In this population-based study, we found that, after adjusting for confounders, hospital types were not associated with functional outcomes. In addition, for patients who were transferred from a TSC/PSC to a CSC, PSM indicated that outcomes were similar to nontransferred patients. Our findings suggest that patient characteristics are more important than hospital characteristics in determining outcome after ICH. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03956485.

Evolution of quality indicators in acute stroke during the RACECAT Trial: Impact in the general population.

BACKGROUND: Acute ischemic stroke patients not referred directly to a comprehensive stroke center (CSC) have reduced access to endovascular treatment (EVT). The RACECAT trial is a population-based cluster-randomized trial, designed to compare mothership and drip-and-ship strategies in acute ischemic stroke patients outside the catchment area of a CSC. AIMS: To analyze the evolution of performance indicators in the regions that participated in RACECAT. METHODS: This retrospective longitudinal observational study included all stroke alerts evaluated by emergency medical services in Catalonia between February 2016 and February 2020. Cases were classified geographically according to the nearest SC: local SC (Local-SC) and CSC catchment areas. We analyzed the evolution of EVT rates and relevant workflow times in Local-SC versus CSC catchment areas over three study periods: P1 (February 2016 to April 2017: before RACECAT initiation), P2 (May 2017 to September 2018), and P3 (October 2018 to February 2020). RESULTS: We included 20603 stroke alerts, 10,694 (51.9%) of which were activated within Local-SC catchment areas. The proportion of patients receiving EVT within Local-SC catchment areas increased (P1 vs. P3: 7.5% (95% confidence interval (CI), 6.4-8.7) to 22.5% (95% CI, 20.8-24.4) p < 0.001). Inequalities in the odds of receiving EVT were reduced for patients from CSC versus Local-SC catchment areas (P1: odds ratio (OR) 3.9 (95% CI, 3.2-5) vs. P3: OR 1.5 (95% CI, 1.3-1.7) In Local-SC, door-to-image (P1: 24 (interquartile range (IQR) 15-36), P2: 24 (15-35), P3: 21 (13-32) min, p < 0.001) and door-to-needle times (P1: 42 (31-60), P2: 41 (29-58), P3: 35 (25-50) p < 0.001) reduced. Time from Local-SC arrival to groin puncture also decreased over time (P1: 188 [151-229], P2: 190 (157-233), P3: 168 (127-215) min, p < 0.001). CONCLUSION: An increase in EVT rates in Local-SC regions with a significant decrease in workflow times occurred during the period of the RACECAT trial.

Sex and gender differences in acute stroke care: metrics, access to treatment and outcome. A territorial analysis of the Stroke Code System of Catalonia.

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. RESULTS: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, p < 0.001). Women tended to present a worse outcome at 90 days, especially for the group receiving only IVT (good outcome 56.7% vs 63.8%; p < 0.001), but not for the group of patients treated with IVT + MT or MT alone, although sex was not independently associated with clinical outcome in logistic regression analysis (OR 1.07; 95% CI, 0.94-1.23; p = 0.27) nor in the analysis after matching using the propensity score (OR 1.09; 95% CI, 0.97-1.22). DISCUSSION AND CONCLUSION: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself.