Stroke etiologies in patients with COVID-19: the SVIN COVID-19 multinational registry.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. METHODS: We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20-6/16/20). RESULTS: Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p

Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke.

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.

Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study.

INTRODUCTION: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality. METHODS: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis. RESULTS: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer. CONCLUSION: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Facial pain radiating upwards: could the pain of epicrania fugax start in the lower face?

BACKGROUND: Epicrania fugax (EF) is characterized by painful paroxysms starting in a particular area of the head, and rapidly radiating forwards or backwards through the territories of different nerves. In former clinical descriptions, the pain moved between the posterior scalp (C2) and the frontal or periorbital area (V1), either in forward or backward direction. METHODS: We report 5 patients with a paroxysmal EF-type pain starting in the lower face (V2 or V3) and radiating upwards. RESULTS: In each patient, the pain stemmed from the cheek (n = 1), the upper lip (n = 2) or the chin and mandibular area (n = 2), and then moved up to the forehead or the scalp with linear trajectory. Pain intensity was moderate (n = 1) or severe (n = 4), and pain quality was stabbing (n = 2) or electric (n = 3). The duration of attacks was very brief, lasting 1 to a few seconds. Three patients had ocular or nasal autonomic accompaniments, and 3 had triggers. CONCLUSIONS: There seems to be a facial variant of EF. These observations could not only expand the clinical spectrum of EF but also enlarge the differential diagnosis of facial pain.

Intracranial atherosclerotic plaque enhancement and long-term risk of future strokes: A prospective, longitudinal study.

BACKGROUND AND PURPOSE: The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients. METHODS: This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves. RESULTS: Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of >1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio >1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio >1.77 had a lower survival free of events (p < .05). CONCLUSIONS: High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.

Safety and feasibility of transradial use of 8F balloon guide catheter Flowgate2 for endovascular thrombectomy in acute ischemic stroke.

BACKGROUND: While Balloon Guide Catheters (BGC) have been shown to increase the rate of reperfusion during mechanical thrombectomy (MT), its implementation with transfemoral approach is at times limited due to unfavorable vascular anatomy. OBJECTIVE: to determine safety, feasibility and performance of the transradial use of 8 F BGC Flowgate2 during mechanical thrombectomy procedures in patients with unfavorable vascular anatomies (type 3 or bovine arch)Material/Methods: We performed a retrospective cohort study of consecutive transradial mechanical thrombectomies performed with BGC Flowgate2 between January and December 2019. Patient demographics, procedural and radiographic metrics, and clinical data were analyzed. RESULTS: 20 (8.7%) out of 230 overall thrombectomy procedures underwent transradial approach using an 8 F BGC Flowgate.2 Successful approach was achieved in 17/20 cases, and in 3 cases radial was switched to femoral, after failure. TICI 2 C/3 was achieved in 18 cases (90%), followed by TICI 2 b and 2a in 1 (5%) case respectively. The average number of passes was 1.8. The average radial puncture-to-first pass time was 22 min. Radial vasospasm was observed in 3/20 cases. The Flowgate2 was found kinked in 4/20 cases (20%), all of them during right internal carotid procedures. There were no postprocedural complications at puncture site, as hematoma, pseudoaneurysm or local ischemic events. CONCLUSION: The use of 8 F Balloon Guide Catheter during MT via transradial approach might represent an alternative in selected cases with unfavorable vascular anatomies. Its use in right ICA catheterizations was associated with a high rate of catheter kinking.

Neurological symptoms in Covid-19 patients in the emergency department.

BACKGROUND: Coronavirus disease 2019 (Covid-19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis. METHODS: Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid-19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log-rank test. RESULTS: We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid-19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%-99.6%) and 98.1% (95% CI: 95.7%-99.2%), respectively. In the multivariate Cox-regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140-0.916) and altered mental status (HR: 1.867, 95%CI: 1.162-3.001) were significant. CONCLUSION: Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid-19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. AIM: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. METHODS: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). RESULTS: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. CONCLUSIONS: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Quantified ischemic core's radiological hypodensity and risk of parenchymal hematoma in > 4.5 h-window stroke thrombectomy.

We aimed to study the relationship between the ischemic core's (IC) radiological hypodensity and the risk of parenchymal haematoma after endovascular therapy (EVT) in acute ischemic stroke (AIS) presenting > 4.5 h from onset. We studied AIS patients with a proximal anterior circulation occlusion > 4.5 h from symptoms onset treated with primary EVT. The IC regions of interest (ROI) were manually delineated on pretreatment CT within the affected hemisphere and their specular ROIs on the unaffected side. IC hypodensity ratio was calculated by dividing mean Hounsfield Unit (HU) value from all ROIs in affected/unaffected hemisphere. Primary endpoint: parenchymal hematoma (PH) type hemorrhagic transformation. Secondary: poor long-term clinical outcome. From May 2015 to November 2018, 648 consecutive AIS patients received reperfusion therapies and 107 met all inclusion criteria. PH after EVT was diagnosed in 33 (31%) patients. In bivariate analyses, IC hypodensity ratio (p < 0.001) and minimum HU value (p = 0.008) were associated with PH. A lower IC hypodensity ratio [OR < 0.001 (< 0.001-0.116) p 0.016] predicted PH but not poor clinical outcome in multivariable logistic regression models. A lower IC radiological density predicted a higher risk of PH in > 4.5 h-window AIS patients treated with primary EVT, although it was not independently associated with a worse clinical outcome.

Anosmia is associated with lower in-hospital mortality in COVID-19.

BACKGROUND: Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity. METHODS: Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression. RESULTS: We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069-0.472) and ICU admission (OR: 0.438, 95% CI: 0.229-0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18-3.28), headache (OR: 2.58, 95% CI: 1.66-4.03), and myalgia (OR: 1.74, 95% CI: 1.12-2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40-1.34), lymphocytes (+849.24, 95% CI: 157.45-1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14-10.71), and lower D-dimer (-4886.52, 95% CI: -8655.29-(-1117.75)), and C-reactive protein (-24.92, 95% CI: -47.35-(-2.48)). CONCLUSIONS: Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response.

Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

OnabotulinumtoxinA treatment for chronic migraine: experience in 52 patients treated with the PREEMPT paradigm.

OnabotulinumtoxinA (OnabotA) was approved for treatment of chronic migraine (CM) after publication of PREEMPT trials. Thus, we set out to evaluate the efficacy of OnabotA in a series of patients with CM treated according to the PREEMPT protocol. In May 2012 we began to offer OnabotA to patients with CM who did not respond to topiramate and at least one other preventive therapy (beta blocker and/or calcium channel antagonist). We prospectively recorded demographic data and the characteristics of migraine, and we assessed the modifications in monthly headache and migraine days, as well as the number of days of symptomatic medication and triptan intake. By September 2014 we had treated 52 patients (8 male, 44 female), whose age at treatment onset was 42.8 ± 12.7 years (range: 16-71) and age at migraine onset was 16.8 ± 7.8 years (3-32). In 43 of these patients (82.7%) symptomatic overuse of medication was observed at the onset of treatment. A total of 168 procedures were performed and after the first session, we observed a significant reduction in all the variables considered. Twelve (23.1%) patients failed to perceive a positive effect after the first procedure and it was not repeated in 4 of them. By contrast, there was a significant decreasing in all the variables evaluated compared to the baseline in the 39 patients that received a second series of injections. The use of OnabotA according to the PREEMPT paradigm is an effective treatment in patients with chronic migraine in a real-life setting.