Seroprevalence of SARS-CoV-2 in Patients with Multiple Sclerosis under Disease-Modifying Therapies: A Multi-Centre Study.

BACKGROUND: The EMCOVID project conducted a multi-centre cohort study to investigate the impact of COVID-19 on patients with Multiple Sclerosis (pwMS) receiving disease-modifying therapies (DMTs). The study aimed to evaluate the seroprevalence and persistence of SARS-CoV-2 antibodies in MS patients enrolled in the EMCOVID database. The DMTs were used to manage MS by reducing relapses, lesion accumulation, and disability progression. However, concerns arose regarding the susceptibility of pwMS to COVID-19 due to potential interactions between SARS-CoV-2 and the immune system, as well as the immunomodulatory effects of DMTs. METHODS: This prospective observational study utilized data from a Multiple Sclerosis and COVID-19 (EMCOVID-19) study. Demographic characteristics, MS history, laboratory data, SARS-CoV-2 serology, and symptoms of COVID-19 were extracted for pwMS receiving any type of DMT. The relationship between demographics, MS phenotype, DMTs, and COVID-19 was evaluated. The evolution of SARS-CoV-2 antibodies over a 6-month period was also assessed. RESULTS: The study included 709 pwMS, with 376 patients providing samples at the 6-month follow-up visit. The seroprevalence of SARS-CoV-2 antibodies was higher among pwMS than the general population, with Interferon treatment being significantly associated with greater seroprevalence (16.9% vs. 8.4%; p 0.003). However, no other specific DMT showed a significant association with antibody presence. A total of 32 patients (8.5%) tested positive for IgG, IgM, or IgA antibodies against SARS-CoV-2 at baseline, but then tested negative at 6 months. Most of the pwMS in the cohort were asymptomatic for COVID-19 and, even among symptomatic cases, the prognosis was generally favourable. CONCLUSION: pwMS undergoing DMTs exhibited a higher seroprevalence of COVID-19 than the general population. Interferon treatment was associated with a higher seroprevalence, suggesting a more robust humoral response. This study provides valuable insights into the seroprevalence and persistence of SARS-CoV-2 antibodies in pwMS and contributes to our understanding of the impact of COVID-19 amongst this population.

Hopelessness in Patients with Early-Stage Relapsing-Remitting Multiple Sclerosis.

Background: Hopelessness is a risk factor for depression and suicide. There is little information on this phenomenon among patients with relapsing-remitting multiple sclerosis (RRMS), one of the most common causes of disability and loss of autonomy in young adults. The aim of this study was to assess state hopelessness and its associated factors in early-stage RRMS. Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The State-Trait Hopelessness Scale (STHS) was used to measure patients´ hopelessness. A battery of patient-reported and clinician-rated measurements was used to assess clinical status. A multivariate logistic regression analysis was conducted to determine the association between patients' characteristics and state hopelessness. Results: A total of 189 patients were included. Mean age (standard deviation-SD) was 36.1 (9.4) years and 71.4% were female. Median disease duration (interquartile range-IQR) was 1.4 (0.7, 2.1) years. Symptom severity and disability were low with a median EDSS (IQR) score of 1.0 (0, 2.0). A proportion of 65.6% (n=124) of patients reported moderate-to-severe hopelessness. Hopelessness was associated with older age (p=0.035), depressive symptoms (p=<0.001), a threatening illness perception (p=0.001), and psychological and cognitive barriers to workplace performance (p=0.029) in the multivariate analysis after adjustment for confounders. Conclusion: Hopelessness was a common phenomenon in early-stage RRMS, even in a population with low physical disability. Identifying factors associated with hopelessness may be critical for implementing preventive strategies helping patients to adapt to the new situation and cope with the disease in the long term.

Delayed cognitive processing and treatment status quo bias in early-stage multiple sclerosis.

BACKGROUND: The evolving therapeutic landscape requires more participation of patients with relapsing remitting multiple sclerosis (RRMS) in treatment decisions. The aim of this study was to assess the association between patient's self-perception, cognitive impairment and behavioral factors in treatment choices in a cohort of patients at an early stage of RRMS. METHODS: We conducted a multicenter, non-interventional study including adult patients with a diagnosis of RRMS, a disease duration ≤18 months and receiving care at one of the 21 participating MS centers from across Spain. We used patient-reported measures to gather information on fatigue, mood, quality of life, and perception of severity of their MS. Functional metrics (Expanded Disability Status Scale [EDSS], cognitive function by the Symbol Digit Modalities Test [SDMT], 25-foot walk test) and clinical and radiological data were provided by the treating neurologist. The primary outcome of the study was status quo (SQ) bias, defined as participant's tendency to continue taking a previously selected but inferior treatment when intensification was warranted. SQ bias was assessed based on participants treatment preference in six simulated RRMS case scenarios with evidence of clinical relapses and radiological disease progression. RESULTS: Of 189 participants who met the inclusion criteria, 188 (99.5%) fully completed the study. The mean age was 36.6 ± 9.5 years, 70.7% female, mean disease duration: 1.2 ± 0.8 years, median EDSS score: 1.0 [IQR=0.0-2.0]). Overall, 43.1% patients (n = 81/188) had an abnormal SDMT (≤49 correct answers). SQ bias was observed in at least one case scenario in 72.3% (137/188). Participant's perception of their MS severity was associated with higher SQ bias (ß coeff 0.042; 95% CI 0.0074-0.076) among those with delayed cognitive processing. Higher baseline EDSS and number of T2 lesions were predictors of delayed processing speed (OR EDSS=1.57, 95% CI: 1.11-2.21, p = 0.011; OR T2 lesions=1.50, 95% CI: 1.11-2.03, p<0.01). Bayesian multilevel model accounting for clustering showed that delayed cognitive processing (exp coeff 1.06; 95% CI 1.04-1.09) and MS symptoms severity (exp coeff 1.28; 95% CI 1.22-1.33) were associated with SQ bias. CONCLUSION: Over 40% of patients in earlier stages of RRMS experience delays in cognitive processing that might affect their decision-making ability. Our findings suggest that patients' self-perception of disease severity combined with a delay in cognitive processing would affect treatment choices leading to status quo bias early in the course of their disease.

Efecto mediador del engagement entre la Felicidad Subjetiva y el Conflicto Trabajo -Familia/ Familia- Trabajo en una muestra de profesores chilenos / Mediating effect of the engagement between Happiness and Conflict Work - Family, / Family - Work in a sample of Chilean teachers

Resumen. Este estudio analizó el efecto mediador del engagement en la relación entre la felicidad subjetiva y el conflicto familia trabajo (CFT) trabajo- familia (CTF). La muestra fue de 190 profesores de la ciudad de Los Ángeles, Chile. Se aplicaron tres escalas previamente validadas en el medio nacional referentes a felicidad subjetiva, conflicto trabajo familia, conflicto familia trabajo y engagement, posteriormente se realizaron modelos de regresión lineal y ecuaciones estructurales para probar las diferentes hipótesis. Los principales resultados evidencian que existe un efecto mediador parcial del engagement sobre la relación entre la felicidad subjetiva y el conflicto familia trabajo /conflicto trabajo-familia, evidenciando en los análisis de regresión que el elemento entusiasmo del engagement presenta un rol predictor en las distintas causas del conflicto.

Abstract. This study analyzed the mediating effect of engagement on the relationship between subjetive happiness and family-work conflict (CFT) and work-family (CTF). The sample was 190 teachers from the city of Los Angeles, Chile. Three scales previously validated in the national environment were applied, on subjetive happiness, work-family conflict, family work and engagement, then linear regression models and structural equations were made to test the different hypotheses. The main results show that there is a partial mediating effect of engagement on the relationship between subjetive happiness and the family-work-family conflict, showing in the regression analyses that the enthusiasm element of engagement presents a predictive role in the different causes of the conflict.

Measuring productivity loss in early relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their autonomy and capacity to maintain employment. OBJECTIVE: The aim of this study was to assess the impact on work productivity in early-stage relapsing-remitting multiple sclerosis (RRMS). METHODS: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. Absenteeism, presenteeism, and unpaid work loss due to RRMS were measured using the Valuation of Lost Productivity (VOLP) questionnaire. The EDSS, SymptoMScreen, 5-item Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale, Symbol Digit Modalities Test, and Multiple Sclerosis Work Difficulties Questionnaire were used to gather information on disability, patients' perception of symptom severity, fatigue, mood/anxiety, cognition, and problems in the workplace, respectively. Associations between the VOLP and clinical and work outcomes were analyzed using Spearman's rank correlations. RESULTS: A total of 189 patients were included. Mean age (SD) was 36.1 ± 9.4 years and 71.4% were female. Mean disease duration was 1.2 ± 0.8 years. Median EDSS score was 1.0 (IQR 0, 2.0). One hundred thirty patients (68.8%) were working for pay or self-employed. Fifty-three patients (40.8%) reported absence from work in the past 3 months with an average of 14.3 absent workdays. Their health problems resulted in the loss of 3.4% of their actual work time in the past 7 days. Thirty patients got help (11.8 h) with their unpaid work activities in the past 7 days. Absenteeism was significantly correlated with anxiety and depression (rho=0.298 and 0.291, p<0.001), fatigue (rho=0.214, p = 0.014), and symptom severity (rho=0.213, p = 0.015). Presenteeism was significantly correlated with fatigue (rho=0.375, p<0.001), symptom severity (rho=0.373, p<0.001), depression (rho=0.263, p = 0.008), and disability (rho=0.215, p = 0.031). CONCLUSIONS: Productivity loss even in a RRMS population with short disease duration stresses the need for more efficient treatment control of disease activity from earlier stages.

Novel Morphological Glial Alterations in the Spectrum of Prion Disease Types: A Focus on Common Findings.

Human prion diseases are a group of rare fatal neurodegenerative diseases with sporadic, genetic, and acquired forms. They are neuropathologically characterized by pathological prion protein accumulation, neuronal death, and vacuolation. Classical immunological response has long been known not to play a major in prion diseases; however, gliosis is known to be a common feature although variable in extent and poorly described. In this investigation, astrogliosis and activated microglia in two brain regions were assessed and compared with non-neurologically affected patients in a representative sample across the spectrum of Creutzfeldt-Jakob disease (CJD) forms and subtypes in order to analyze the influence of prion strain on pathological processes. In this report, we choose to focus on features common to all CJD types rather than the diversity among them. Novel pathological changes in both glial cell types were found to be shared by all CJD types. Microglial activation correlated to astrogliosis. Spongiosis, but not pathological prion protein deposition, correlated to both astrogliosis and microgliosis. At the ultrastructural level, astrocytic glial filaments correlated with pathological changes associated with prion disease. These observations confirm that neuroglia play a prominent role in the neurodegenerative process of prion diseases, regardless of the causative prion type.

Neuroimmune Response Mediated by Cytokines in Natural Scrapie after Chronic Dexamethasone Treatment.

The actual role of prion protein-induced glial activation and subsequent cytokine secretion during prion diseases is still incompletely understood. The overall aim of this study is to assess the effect of an anti-inflammatory treatment with dexamethasone on different cytokines released by neuroglial cells that are potentially related to neuroinflammation in natural scrapie. This study emphasizes the complex interactions existent among several pleiotropic neuromodulator peptides and provides a global approach to clarify neuroinflammatory processes in prion diseases. Additionally, an impairment of communication between microglial and astroglial populations mediated by cytokines, mainly IL-1, is suggested. The main novelty of this study is that it is the first one assessing in situ neuroinflammatory activity in relation to chronic anti-inflammatory therapy, gaining relevance because it is based on a natural model. The cytokine profile data would suggest the activation of some neurotoxicity-associated route. Consequently, targeting such a pathway might be a new approach to modify the damaging effects of neuroinflammation.

D-Dimer as Predictor of Large Vessel Occlusion in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Improving prehospital triage of large vessel occlusion (LVO) would reduce time to reperfusion therapies. We aimed to study early predictors of LVO in acute ischemic stroke to identify candidates for endovascular treatment. METHODS: The Stroke-Chip was a prospective observational study conducted at 6 Stroke Centers in Catalonia. Blood samples were obtained in the first 6 hours from symptom onset of consecutive patients. Stroke severity was evaluated with National Institutes of Health Stroke Scale (NIHSS) and LVO was assessed. Independent association of multiple blood biomarkers with LVO was evaluated using logistic regression models adjusted by covariates. Sensitivity, specificity, and predictive values were assessed for NIHSS and the combination of NIHSS and selected serum biomarkers levels. RESULTS: One thousand three hundred eight suspected strokes were enrolled for a 17-month period. LVO was not assessed in 131 patients. One thousand one hundred seventy-seven patients were selected for analysis (mean age 69.3 years, 56% men, median baseline NIHSS of 6, and median time to blood collection 2.5 hours). LVO was detected in 262 patients. LVO patients were older, had higher baseline NIHSS, history of atrial fibrillation, and lower time from stroke onset to admission. After logistic regression analysis, D-dimer remained an independent predictor of LVO (odds ratio, 1.59 [1.31-1.92]). Specificity and positive predictive value to exclude or detect LVO were higher when using combined D-dimer levels and NIHSS score assessment rather than NIHSS alone. CONCLUSIONS: Early D-dimer levels are an independent predictor of LVO and may be useful to better optimize prehospital patient transport to the appropriate stroke center.

Neuroimmune Response in Natural Preclinical Scrapie after Dexamethasone Treatment.

A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease. Herein, we aimed to extend the aforementioned study on the effect of this anti-inflammatory therapy to the initial phase of scrapie, with the aim of elucidating the natural neuroinflammatory process occurring in this neurodegenerative disorder. The administration of this glucocorticoid resulted in an outstanding reduction in vacuolation and aberrant protein deposition (nearly null), and an increase in glial activation. Furthermore, evident suppression of IL-1R and IL-6 and the exacerbation of IL-1α, IL-2R, IL-10R and IFNγR were also demonstrated. Consequently, the early stage of the disease is characterized by an intact neuroglial response similar to that of healthy individuals attempting to re-establish homeostasis. A complex network of neuroinflammatory markers is involved from the very early stages of this prion disease, which probably becomes impaired in the more advanced stages. The in vivo animal model used herein provides essential observations on the pathogenesis of natural scrapie, as well as the possibility of establishing neuroglia as potential target cells for anti-inflammatory therapy.

Assessment of Glial Activation Response in the Progress of Natural Scrapie after Chronic Dexamethasone Treatment.

Neuroinflammation has been correlated with the progress of neurodegeneration in many neuropathologies. Although glial cells have traditionally been considered to be protective, the concept of them as neurotoxic cells has recently emerged. Thus, a major unsolved question is the exact role of astroglia and microglia in neurodegenerative disorders. On the other hand, it is well known that glucocorticoids are the first choice to regulate inflammation and, consequently, neuroglial inflammatory activity. The objective of this study was to determine how chronic dexamethasone treatment influences the host immune response and to characterize the beneficial or detrimental role of glial cells. To date, this has not been examined using a natural neurodegenerative model of scrapie. With this aim, immunohistochemical expression of glial markers, prion protein accumulation, histopathological lesions and clinical evolution were compared with those in a control group. The results demonstrated how the complex interaction between glial populations failed to compensate for brain damage in natural conditions, emphasizing the need for using natural models. Additionally, the data showed that modulation of neuroinflammation by anti-inflammatory drugs might become a research focus as a potential therapeutic target for prion diseases, similar to that considered previously for other neurodegenerative disorders classified as prion-like diseases.

Neuroglial patterns are shared by cerebella from prion and prion-like disorder affected patients.

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are considered prion-like disorders because they are all proteinopathies in which aberrant proteins spread throughout the brain during disease progression. The overall aim of this study is to determine how glial cells are commonly involved in the neurodegeneration progress observed in all these pathologies. The suggestion that they are cell types in which prion and prion-like disorders have common behaviour is the hypothesis on which this study is based. Morphological and distribution differences in astroglial and microglial cells in the cerebellum from prion and prion-like disease-affected patients were assessed here by histopathological and immunochemical tools. To our knowledge, this is the first study to focus on the comparative assessment of glial profiles in these human brains. Activated microglial population was demonstrated in both, prion and prion-like disorders, although in higher extent in the first. In astroglial activation, specific patterns of alterations suggesting both degenerative and potentially neuroprotective or restorative stem cell response, were shown to be alternatively shared by cerebella from all disorders studied. Neuro-protective strategies for these disabling disorders are particularly desirable.

Age- and Sex-Specific Risk Profiles and In-Hospital Mortality in 13,932 Spanish Stroke Patients.

BACKGROUND: In-hospital stroke death rate is an important sanitary issue. Despite advances in the acute phase management of stroke patients, mortality and disability rates remain high. In aging populations and with different mortality between the sexes in general, the study of sex- and age-related differences becomes increasingly relevant for optimization of post-acute clinical care of stroke patients. METHODS: We designed a cohort follow-up study with 13,932 consecutive ischemic stroke (IS) patients from 19 Spanish hospitals. Data was obtained from the Spanish Stroke Registry; transient ischemic attacks and ages <18 years were excluded. Patients were organised by age group and sex. We compared female and male patient cohorts within and across age groups univariately and used multivariable logistic regression to adjust for confounders in differential in-hospital mortality. RESULTS: The median (percentiles 2.5 and 97.5%) age was 78 (41-92) years old for women and 71 (41-92) for men. IS women were more likely to be older, to exhibit cardio-embolic aetiology, and less likely to have been admitted to a stroke unit or to have had a stroke code activated. Both pre-stroke modified Rankin Scale and National Institute of Health Stroke Scale (NIHSS) scores at admission increased significantly with age and were higher in women than those in men. Differences in distributions of common risk factors for IS and of in-hospital outcomes between women and men actually changed with patient's age. It is to be noted here that although there were no statistically significant differences (p > 0.05) between the sexes within any age group, in-hospital mortality appeared significantly higher in women than that in men when analysed overall, due to confounding. Death was more closely related to stroke in women than in men and occurred earlier. Although there were some age-specific sex differences between the predictors for in-hospital mortality, stroke severity measured by NIHSS was the main predictor of in-hospital mortality for both sexes. Topographic classifications - partial anterior circulatory infarct and total anterior circulatory infarct - were significant prognostic factors for men aged <60 years and for those in the 60-69 years range respectively. CONCLUSION: Although most of our findings were consistent with previous studies, it is important to take into account and highlight differences in in-hospital mortality between the sex and age group. Not to account for age-related differences between the sexes can give false results that may mislead management decisions. As most deaths in women were related to stroke, it is important to improve their early management, stroke code activation, access to stroke units and/or revascularisation therapies, especially in the older age groups.

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.

Glial alterations in human prion diseases: A correlative study of astroglia, reactive microglia, protein deposition, and neuropathological lesions.

BACKGROUND: Neuroinflammation has recently been proposed to be a major component of neurodegenerative diseases. The aim of this study was to determine how the interaction between microglia and astroglia, which are the primary immune cell populations in the brain, and pathological prion protein (PrPsc) could influence the development and propagation of this neurodegenerative disease. Because a relevant role for glial response in prion disease has been clearly demonstrated in our previous studies using the natural animal model, a similar approach has been taken here using the natural human model. METHODS: A morphological approach has been developed to analyze cerebellar samples from patients with Creutzfeldt-Jakob disease (CJD) in comparison with healthy control cases. Histopathological lesions were assessed, and PrPsc, glial fibrillary acidic protein (GFAP) and reactive microglia were immunolabelled by specific antibodies. Furthermore, co-location studies using confocal microscopy were performed to determine the possible relationships between both types of glial cells in all samples. RESULTS: The results presented in this study support the involvement of both types of glial cells in CJD. Evidence of increased astrocyte and microglia reactivity can be observed in all CJD cases, and a close relationship between the types of glia is demonstrated by co-location studies. CONCLUSION: Proteinopathies such as Alzheimer, Parkinson, and Huntington diseases, where aberrant proteins spread throughout the brain during disease progression, may share a molecular basis and mechanisms of propagation. Therefore, studies elucidating the interaction between gliosis and prion propagation may be relevant to these other neurodegenerative diseases and may provide new targets for therapeutic intervention.

Statins do not increase Markers of Cerebral Angiopathies in patients with Cardioembolic Stroke.

We investigated whether pre-treatment with statins is associated with surrogate markers of amyloid and hypertensive angiopathies in patients who need to start long-term oral anticoagulation therapy. A prospective multicenter study of patients naive for oral anticoagulants, who had an acute cardioembolic stroke. MRI was performed at admission to evaluate microbleeds, leukoaraiosis and superficial siderosis. We collected data on the specific statin compound, the dose and the statin intensity. We performed bivariate analyses and a logistic regression to investigate variables associated with microbleeds. We studied 470 patients (age 77.5 ± 6.4 years, 43.7% were men), and 193 (41.1%) of them received prior treatment with a statin. Microbleeds were detected in 140 (29.8%), leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The presence of microbleeds, leukoaraiosis or superficial siderosis was not related to pre-treatment with statins. Microbleeds were more frequent in patients with prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06-90.9) and in those pre-treated antiplatelets (OR 1.66, 95% CI 1.09-2.53). Prior treatment with statins was not associated with markers of bleeding-prone cerebral angiopathies in patients with cardioembolic stroke. Therefore, previous statin treatment should not influence the decision to initiate or withhold oral anticoagulation if these neuroimaging markers are detected.

Blood Biomarkers for the Early Diagnosis of Stroke: The Stroke-Chip Study.

BACKGROUND AND PURPOSE: Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase. METHODS: The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves. RESULTS: From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71; P<0.0001) and endostatin >4.7 (odds ratio, 2.02; 95% confidence interval, 1.19-3.45; P=0.010), together with age, sex, blood pressure, stroke severity, atrial fibrillation, and hypertension, were included in the model. Predictive accuracy was 80.6%. CONCLUSIONS: The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.

Influence of Hospital Type on Outcomes of Individuals Aged 80 and Older with Stroke Treated Using Intravenous Thrombolysis.

OBJECTIVES: The aim of the study was to confirm the safety and effectiveness of using intravenous thrombolysis (IVT) with individuals aged 80 and older in routine practice in different hospital settings. DESIGN: Observasional registry. SETTING: Prospective multicenter population-based registry of acute stroke patients treated with reperfusion therapies in Catalonia, Spain (Sistema Online d'Informació de l'Ictus Agut). PARTICIPANTS: Individuals treated only with IVT (N = 3,231; 1,189 (36.8%) aged ≥80). MEASUREMENTS: Symptomatic intracranial hemorrhage, mortality, and favorable outcome (modified Rankin Scale (mRS) score = 0-2) at 3 months were evaluated according to hospital characteristics. Treating hospitals were classified in three categories: comprehensive stroke centers (CSCs), primary stroke centers (PSCs), and community hospitals operating a telestroke system (TS). First individuals aged 80 and older were compared with those younger than 80, and then participants aged 80 and older were focused on. RESULTS: Participants aged 80 and older had significantly higher baseline National Institute of Health Stroke Scale (NIHSS) scores, longer onset to treatment times, and worse outcomes than younger participants. For participants aged 80 and older, 90-day mortality was 23.2%, with 38.7% having favorable outcomes at 3 months. Symptomatic intracranial hemorrhage (SICH; Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy definition) was observed in 4.7% of subjects. None of the risk factors differed significantly between participants treated in different types of hospitals. Basal stroke severity measured according to NIHSS score was not significantly different either. The three different types of hospitals achieved similar outcomes, although the TS and PSC hospitals had significantly higher proportions of SICH (6.3% and 6.3%, respectively) than the CSC (3.2%). CONCLUSION: Older adults with acute stroke treated with IVT had similar outcomes regardless of hospital characteristics.

Risk factors are different for deep and lobar remote hemorrhages after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Remote parenchymal haemorrhage (rPH) after intravenous thrombolysis is defined as hemorrhages that appear in brain regions without visible ischemic damage, remote from the area of ischemia causing the initial stroke symptom. The pathophysiology of rPH is not clear and may be explained by different underlying mechanisms. We hypothesized that rPH may have different risk factors according to the bleeding location. We report the variables that we found associated with deep and lobar rPH after intravenous thrombolysis. METHODS: This is a descriptive study of patients with ischemic stroke who were treated with intravenous thrombolysis. These patients were included in a multicenter prospective registry. We collected demographic, clinical and radiological data. We evaluated the number and distribution of cerebral microbleeds (CMB) from Magnetic Resonance Imaging. We excluded patients treated endovascularly, patients with parenchymal hemorrhage without concomitant rPH and stroke mimics. We compared the variables from patients with deep or lobar rPH with those with no intracranial hemorrhage. RESULTS: We studied 934 patients (mean age 73.9±12.6 years) and 52.8% were men. We observed rPH in 34 patients (3.6%); 9 (0.9%) were deep and 25 (2.7%) lobar. No hemorrhage was observed in 900 (96.6%) patients. Deep rPH were associated with hypertensive episodes within first 24 hours after intravenous thrombolysis (77.7% vs 23.3%, p<0.001). Lobar rPH were associated with the presence of CMB (53.8% vs 7.9%, p<0.001), multiple (>1) CMB (30.7% vs 4.4%, p = 0.003), lobar CMB (53.8% vs 3.0%, p<0.001) and severe leukoaraiosis (76.9% vs 42%, p = 0.02). CONCLUSIONS: A high blood pressure within the first 24 hours after intravenous thrombolysis is associated with deep rPH, whereas lobar rPH are associated with imaging markers of amyloid deposition. Thus, our results suggest that deep and lobar rPH after intravenous thrombolysis may have different mechanisms.

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.

Access to Endovascular Treatment in Remote Areas: Analysis of the Reperfusion Treatment Registry of Catalonia.

BACKGROUND AND PURPOSE: Since demonstration of the benefit of endovascular treatment (EVT) in acute ischemic stroke patients with proximal arterial occlusion, stroke care systems need to be reorganized to deliver EVT in a timely and equitable way. We analyzed differences in the access to EVT by geographical areas in Catalonia, a territory with a highly decentralized stroke model. METHODS: We studied 965 patients treated with EVT from a prospective multicenter population-based registry of stroke patients treated with reperfusion therapies in Catalonia, Spain (SONIIA). Three different areas were defined: (A) health areas primarily covered by Comprehensive Stroke Centers, (B) areas primarily covered by local stroke centers located less than hour away from a Comprehensive Stroke Center, and (C) areas primarily covered by local stroke centers located more than hour away from a Comprehensive Stroke Center. We compared the number of EVT×100 000 inhabitants/year and time from stroke onset to groin puncture between groups. RESULTS: Baseline characteristics were similar between groups. Throughout the study period, there were significant differences in the population rates of EVT across geographical areas. EVT rates by 100 000 in 2015 were 10.5 in A area, 3.7 in B, and 2.7 in C. Time from symptom onset to groin puncture was 82 minutes longer in group B (312 minutes [245-435]) and 120 minutes longer in group C (350 minutes [284-408]) compared with group A (230 minutes [160-407]; P<0.001). CONCLUSIONS: Accessibility to EVT from remote areas is hampered by lower rate and longer time to treatment compared with areas covered directly by Comprehensive Stroke Centers.