A nationwide Guillain-Barré syndrome epidemiological study in Spain during the COVID-19 years.

BACKGROUND AND PURPOSE: The purpose was to perform a nationwide epidemiological study of Guillain-Barré syndrome (GBS) in Spain, analysing background incidences and seasonal variation and trying to identify incidence changes during the coronavirus disease 2019 (COVID-19) years. METHODS: This was an observational study collecting all GBS diagnoses from the National Epidemiological Surveillance Network collected by the Ministry of Health. Patients discharged with GBS as the main diagnosis and admitted during 2018-2021 were included. Data on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were obtained from the National Epidemiology Centre. RESULTS: In total, 3147 cases were included, 832 in 2018, 861 in 2019, 670 in 2020 and 784 in 2021. Nationwide hospital incidence was 1.78 in 2018, 1.71 in 2019, 1.41 in 2020 and 1.66 in 2021, with an increased frequency in males, the elderly population and in the winter season. Eleven per cent of GBS patients needed ventilatory support. GBS and SARS-CoV-2 incidences did not correlate with one another (r = -0.29, p = 0.36). GBS incidence decreased during 2020 and during the COVID-19 lockdown period in comparison to the same months of 2018-2019. CONCLUSIONS: The incidence of GBS in Spain is similar to that of other countries. Despite prior reports describing a significant increase in COVID-19-associated GBS in Spain, a significant drop of GBS incidence during the SARS-CoV-2 pandemic was detected, probably due to prevention measures.

Neuromodulation of Executive Dysfunction in Patients with Acute Stroke Using Transcranial Direct Current Stimulation: Study Protocol for a Triple-Blind, Randomized Sham-Controlled Trial.

Research on the benefits of non-invasive brain stimulation in stroke patients to improve executive functions is scarce. The objective of this study was to investigate the effectiveness of transcranial direct current stimulation (tDCS) in combination with cognitive training for the rehabilitation of executive functions in acute and subacute stroke patients as well as to explore the underlying physiological mechanisms. A triple-blinded, randomized-controlled clinical trial will be conducted involving 60 stroke patients with frontal or basal ganglia lesions and a Montreal Cognitive Assessment (MoCA) score less than 26. Participants will be randomly assigned to receive active tDCS (anode over the left dorsolateral prefrontal cortex, cathode at the right supraorbital region, 20 min at 2 mA) or sham tDCS in a 1:1 ratio for 10 sessions, followed by targeted executive function training. The primary efficacy outcome will be the MoCA score, while secondary outcomes will include the five-digit test (inhibitory control), the Digit Span Task (working memory), the abbreviated version of the Wisconsin Card Sorting test (cognitive flexibility), modified Rankin scale (functional state), Beck-II depression inventory, apathy evaluation scale, and the WHOQOL-BREF (quality of life), assessed immediately after the intervention and at 1, 3, 6, and 12 months post-intervention. Additionally, resting-state functional connectivity and blood biomarkers, such as neurotrophins, growth factors, and inflammatory molecules, will be evaluated before and after the intervention. This study will contribute to the investigation of the efficacy of tDCS in rehabilitating executive functions in acute and subacute stroke patients. The multidimensional approach utilized in this study, which includes analysis of resting-state connectivity and neuroplasticity-related blood biomarkers, is expected to provide insights into the underlying brain mechanisms involved in the rehabilitation of dysexecutive syndrome.

Related factors with orolingual angioedema after intravenous alteplase in acute ischemic stroke: results from a single-center cohort and meta-analysis.

INTRODUCTION: Orolingual angioedema (OA) after intravenous thrombolysis (IVT) with alteplase in acute stroke can be a life-threatening complication. Our aim was to describe its incidence, clinical features, and related factors. PATIENTS AND METHODS: We analyzed a single-center cohort of stroke patients treated with IVT in an 8-year period. We compared patients with (OA+) and without OA (OA-). A meta-analysis of previous studies was performed to identify factors related with OA. RESULTS: OA occurred in 7 out of 512 patients (1.37%; 95% CI 0.86-1.88%). Previous hypertension, diabetes, and treatment with ACE inhibitors were more frequent in OA+ compared to OA- patients (100% vs 58%, p = 0.045; 71.4% vs 21.8%, p = 0.008; and 71.4% vs. 16.6%, p = 0.002). Three out of 4 cases with unilateral OA had a contralateral insular infarct. The meta-analysis included 13 studies: 5720 stroke patients treated with IVT and 209 cases of OA. Factors related with OA were ACE inhibitor treatment (RR 5.33 [95% CI 3.07-9.26]) female sex (RR 1.94 [95% CI 1.24-3.03]), hypertension (RR 2.64 [95% CI 1.79-3.90]), diabetes (RR 1.60 [95% CI 1.16-2.21]), and dyslipidemia (RR 1.46 [95% CI 1.00-2.12]). The effect of insular infarct was inconclusive: positive when considering complete infarcts (RR 1.97 [95% CI 1.18-3.29]) and absent when partial infarcts were also included. CONCLUSIONS: OA occurred in 1.37% of the IVT-treated stroke patients. Previous treatment with ACE inhibitors, hypertension, diabetes, dyslipidemia, and female sex were associated with OA. The effect of insular infarct needs to be clarified in further studies.

Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic.

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.

Acute Stroke Care during the COVID-19 Pandemic: Reduction in the Number of Admissions of Elderly Patients and Increase in Prehospital Delays.

INTRODUCTION: We analyzed whether the coronavirus disease 2019 (COVID-19) crisis affected acute stroke care in our center during the first 2 months of lockdown in Spain. METHODS: This is a single-center, retrospective study. We collected demographic, clinical, and radiological data; time course; and treatment of patients meeting the stroke unit admission criteria from March 14 to May 14, 2020 (COVID-19 period group). Data were compared with the same period in 2019 (pre-COVID-19 period group). RESULTS: 195 patients were analyzed; 83 in the COVID-19 period group, resulting in a 26% decline of acute strokes and transient ischemic attacks (TIAs) admitted to our center compared with the previous year (p = 0.038). Ten patients (12%) tested positive for PCR SARS-CoV-2. The proportion of patients aged 65 years and over was lower in the COVID-19 period group (53 vs. 68.8%, p = 0.025). During the pandemic period, analyzed patients were more frequently smokers (27.7 vs. 10.7%, p = 0.002) and had less frequently history of prior stroke (13.3 vs. 25%, p = 0.043) or atrial fibrillation (9.6 vs. 25%, p = 0.006). ASPECTS score was lower (9 [7-10] vs. 10 [8-10], p = 0.032), NIHSS score was slightly higher (5 [2-14] vs. 4 [2-8], p = 0.122), onset-to-door time was higher (304 [93-760] vs. 197 [91.25-645] min, p = 0.104), and a lower proportion arrived within 4.5 h from onset of symptoms (43.4 vs. 58%, p = 0.043) during the CO-VID-19 period. There were no differences between proportion of patients receiving recanalization treatment (intravenous thrombolysis and/or mechanical thrombectomy) and in-hospital delays. CONCLUSION: We observed a reduction in the number of acute strokes and TIAs admitted during the COVID-19 period. This drop affected especially elderly patients, and despite a delay in their arrival to the emergency department, the proportion of patients treated with recanalization therapies was preserved.

Non-invasive brain stimulation for functional recovery in animal models of stroke: A systematic review.

Motor and cognitive dysfunction occur frequently after stroke, severely affecting a patient´s quality of life. Recently, non-invasive brain stimulation (NIBS) has emerged as a promising treatment option for improving stroke recovery. In this context, animal models are needed to improve the therapeutic use of NIBS after stroke. A systematic review was conducted based on the PRISMA statement. Data from 26 studies comprising rodent models of ischemic stroke treated with different NIBS techniques were included. The SYRCLE tool was used to assess study bias. The results suggest that both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) improved overall neurological, motor, and cognitive functions and reduced infarct size both in the short- and long-term. For tDCS, it was observed that either ipsilesional inhibition or contralesional stimulation consistently led to functional recovery. Additionally, the application of early tDCS appeared to be more effective than late stimulation, and tDCS may be slightly superior to rTMS. The optimal stimulation protocol and the ideal time window for intervention remain unresolved. Future directions are discussed for improving study quality and increasing their translational potential.

Impact of Direct Transport to Thrombectomy-Capable Center vs. Nearby/Distant Local Stroke Centers on Stroke Outcome in Patients Undergoing Thrombectomy: A Real-Life Study.

Our aim was to compare the stroke outcomes of a direct transfer (DT) to a thrombectomy-capable center vs. initial care at two local stroke centers: a nearby hospital (NH, 36 km) and a distant hospital (DH, 113 km). Patients who underwent a mechanical thrombectomy were analyzed (February 2017-October 2021), and the outcome was considered favorable if the modified Rankin scale (mRS) score was ≤ 2 at three months. A total of 300 patients were included, 55 of which were transferred from the NH and 58 from the DH. There was a difference in the median (IQR) transfer time of 39 min between the hospitals (149 min for the NH vs. 188 min for the DH, p = 0.003). After adjusting for confounding variables, a secondary transfer from the DH, compared to a DT, was associated with a lower functional independence: mRS score ≤ 2 (OR = 0.37, 95% CI = 0.14-0.97, p = 0.043), without significant differences in the mortality between the groups. These differences were not observed in patients from the NH. Conclusions: A secondary transfer from a distant hospital was associated with a poorer functional outcome at 3 months. This unfavorable outcome was not observed among patients transferred from a nearby hospital. These findings highlight the importance of categorizing the suitability of one transfer model over another based on the proximity of hospitals to the thrombectomy center, but also in accordance with organizational and geographic characteristics that vary within each health region.

Closing the Sex-Based Differences in Stroke Care: Insights from a Large Telestroke Network on Treatment and Postacute Management.

Background: The evolution of ischemic stroke is different accordin'g to sex and is one of the main causes of death in women. Previous studies have shown that women are less likely to receive acute treatment, and stroke center type is an important predictor of door-to-needle times. We investigated whether women are attended in a similar way to men in the telestroke network with specialized stroke physicians. Methods: A prospective registry of ischemic strokes recorded in the centralized Andalusian telestroke network was analyzed, focusing on sex differences. Demographic data, clinical characteristics, neuroimaging data, treatment intervals, follow-up visits, and clinical outcomes were collected. Results: A total of 3009 suspected stroke patients were attended to in the telestroke network from 2019 to 2023, of which 42.74% were women. Women were older (p < 0.001) and less independent upon arrival (p = 0.006) than men. There was no difference in the treatment received or in the treatment time intervals between the groups. Importantly, there was no difference in modified Rankin scale scores at 3 months between sexes. At 3 months post-stroke follow-up, women had fewer imaging tests (p = 0.018) and fewer outpatient visits (p < 0.001) than men. Conclusions: No significant difference between men and women has been found in the acute treatment of stroke in a large telestroke network. However, the same is not true for the follow-up and management of patients after the acute phase. This fact supports that strict adherence to protocols and specialization of care lead to equal care that avoids sex differences in stroke treatment and functional outcomes.

Evaluation of the effects of a gamified, fully immersive and stroke-specific virtual reality intervention for improving disability and quality of life in patients with stroke in the subacute phase: study protocol of the RESET randomised trial.

Stroke is the leading cause of disability and the second cause of death worldwide. The increasing burden of stroke underscores the importance of optimising rehabilitation protocols. Virtual reality (VR) can improve poststroke prognosis. A VR software combining gamification, full immersion and stroke specificity (ie, the Development and validation of a novel viRtual rEality software for improving diSability and quality of lifE in patients with sTroke (RESET) software) might substantially improve disability and quality of life (QoL). However, this technology is still very scarce. The RESET trial aims to assess the effects of an early 10-week gamified, fully immersive and stroke-specific VR intervention (ie, starting at week 3 poststroke) on disability and QoL in people with stroke in the subacute phase. People with ischaemic or haemorrhagic stroke (n=94) aged ≥ 18 years will be randomised to receive (1) usual care (UC), (2) commercial VR or (3) gamified, fully immersive and stroke-specific VR (RESET). The three groups will receive UC (ie, three sessions/week of 90 min of standard rehabilitation). The VR groups will additionally receive three VR sessions of 20 min per week. The outcome measures will be assessed at baseline (week 2 from stroke occurrence), week 13 (approximately 90 days from the event) and week 26 (approximately 6 months from the event). The primary outcome is disability measured with the Barthel Index. Secondary outcomes include QoL, upper-extremity and lower-extremity motor function, gross manual dexterity, handgrip strength and cognitive function. This study will unravel the effects of a gamified, fully immersive and stroke-specific VR software on disability and QoL in patients with stroke in the early subacute phase.Trial registration number: NCT06132399.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Acute intracranial internal carotid artery occlusion: Extension and location of the thrombus as an influencing factor in Computed Tomography angiography findings.

Purpose: Acute intracranial internal carotid artery (ICA) occlusion can mimic an extracranial affectation on Computed Tomography angiography (CTA). This fact could be explained by the extension of the thrombus in the ICA concerning its arterial branches. This study aims to determine how this factor may influence imaging findings. Methods: A retrospective study was conducted from a single-center database of patients undergoing mechanical thrombectomy due to ICA occlusion between October 2017 and March 2022 (n = 77). Patients with acute intracranial ICA occlusion were included (n = 29) and divided into two groups, according to ICA opacification on CTA: the discernible extracranial ICA or group D, and the pseudo-occlusion or group P. Patency of posterior communicating, anterior choroidal, and ophthalmic arteries on digital subtraction angiography were collected to determine thrombus extension. Sensitivity and specificity were calculated for CTA. Results: Significant differences were found in DSA between group P (n = 17) and group D (n = 12) in the frequency of patency of major artery branches: the presence of posterior communicating (PCOM) and anterior choroidal arteries (AChA) was observed in 2 patients in group P vs. 10 in group D (p < 0.001); whereas the patency of the ophthalmic artery (OA) was visualized in 10 patients in group P vs. 12 in group D, p = 0.023). For the diagnosis of isolated intracranial ICA occlusion, CTA had a sensitivity of 43.5% and a specificity of 97.2%. Conclusions: The location and extent of the thrombus in the intracranial ICA concerning major artery branches may influence CTA findings.

Direct Mechanical Thrombectomy vs. Bridging Therapy in Stroke Patients in A "Stroke Belt" Region of Southern Europe.

The aim of this 4-year observational study is to analyze the outcomes of stroke patients treated with direct mechanical thrombectomy (dMT) compared to bridging therapy (BT) (intravenous thrombolysis [IVT] + BT) based on 3-month outcomes, in real clinical practice in the "Stroke Belt" of Southern Europe. In total, 300 patients were included (41.3% dMT and 58.6% BT). The frequency of direct referral to the stroke center was similar in the dMT and BT group, whereas the time from onset to groin was longer in the BT group (median 210 [IQR 160-303] vs. 399 [IQR 225-675], p = 0.001). Successful recanalization (TICI 2b-3) and hemorrhagic transformation were similar in both groups. The BT group more frequently showed excellent outcomes at 3 months (32.4% vs. 15.4%, p = 0.004). Multivariate analysis showed that BT was independently associated with excellent outcomes (OR 2.7. 95% CI,1.2-5.9, p = 0.02) and lower mortality (OR 0.36. 95% CI 0.16-0.82, p = 015). Conclusions: Compared with dMT, BT was associated with excellent functional outcomes and lower 3-month mortality in this real-world clinical practice study conducted in a region belonging to the "Stroke Belt" of Southern Europe. Given the disparity of results on the benefit of BT in the current evidence, it is of vital importance to analyze the convenience of its use in each health area.

N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated with Post-Stroke In-Hospital Complications.

Previous studies have shown the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) with stroke mortality and functional outcome after an acute ischemic stroke (AIS). Knowledge of its association with systemic and neurological in-hospital complications is scarce. Our objective is to analyze this. We performed an observational, retrospective study that included consecutive AIS patients during a 1-year period (2020). A multivariate analysis was performed to identify if NT-proBNP levels were independently associated with in-hospital complications. 308 patients were included, of whom 96 (31.1%) developed systemic and 62 (20.12%) neurological in-hospital complications. Patients with any complication (39.3%) showed higher NT-proBNP levels than those without (median (IQR): 864 (2556) vs. 142 (623) pg/dL, p < 0.001). The receiver operating characteristic curve (ROC) pointed to 326 pg/dL of NT-proBNP as the optimal cutoff level for developing in-hospital systemic complications (63.6% sensitivity and 64.7% specificity for any complication; 66.7% and 62.7% for systemic; and 62.9% and 57.7% for neurological complications). Multivariate analyses showed that NT-proBNP > 326 pg/dL was associated with systemic complications (OR 2.336, 95% CI: 1.259-4.335), adjusted for confounders. This did not reach statistical significance for neurological complications. NT-proBNP could be a predictor of in-hospital systemic complications in AIS patients. Further studies are needed.

Stroke in Young Adults in Spain: Epidemiology and Risk Factors by Age.

INTRODUCTION: Recent research has highlighted an increased incidence of ischemic stroke (IS) in young adults, along with a higher percentage of vascular risk factors at younger ages. This study aimed to estimate the in-hospital incidence of IS and associated comorbidities by sex and age group in Spain. METHODS: A retrospective analysis of the Spain Nationwide Inpatient Sample database from 2016 to 2019 was conducted, which included adult patients with IS. In-hospital incidence and mortality rates were estimated, and a descriptive analysis of the main comorbidities was performed, stratified by sex and age groups. RESULTS: A total of 186,487 patients were included, with a median age of 77 (IQR 66-85) years and 53.3% were male. Of these, 9162 (5%) were aged between 18 and 50 years. The estimated incidence of IS in adults younger than 50 years ranged from 11.9 to 13.5 per 100,000 inhabitants during the study period, with a higher incidence in men. The overall in-hospital mortality was 12.6%. Young adults with IS had a higher prevalence of most vascular risk factors compared to the general Spanish population, with a specific distribution according to sex and age. CONCLUSIONS: This study provides estimates of the incidence of IS and the prevalence of vascular risk factors and comorbidities associated with IS in Spain, stratified by sex and age, using a national registry of hospital admissions. These findings should be considered in terms of both primary and secondary prevention strategies.

External Validation and Recalibration of a Mortality Prediction Model for Patients with Ischaemic Stroke.

BACKGROUND: Stroke is a highly prevalent disease that can provoke severe disability. We evaluate a predictive model based on the Minimum Basic Data Set (MBDS) compiled by the Spain Health Ministry, obtained for the period 2008-2012 for patients with ischaemic stroke in Spain, to establish the model's validity and to optimise its calibration. The MBDS is the main clinical-administrative database for hospitalisations recorded in Spain, and to our knowledge, no predictive models for stroke mortality have previously been developed using this resource. The main study aim is to perform an external validation and recalibration of the coefficients of this predictive model with respect to a chronologically later cohort. MATERIAL AND METHODS: External validation (testing the model on a different cohort to assess its performance) and recalibration (validation with optimisation of model coefficients) were performed using the MBDS for patients admitted for ischaemic stroke in the period 2016-2018. A cohort study was designed, in which a recalibrated model was obtained by applying the variables of the original model without their coefficients. The variables from the original model were then applied to the subsequent cohort, together with the coefficients from the initial model. The areas under the curve (AUC) of the recalibration and the external validation procedure were compared. RESULTS: The recalibrated model produced an AUC of 0.743 and was composed of the following variables: age (odds ratio, OR:1.073), female sex (OR:1.143), ischaemic heart disease (OR:1.192), hypertension (OR:0.719), atrial fibrillation (OR:1.414), hyperlipidaemia (OR:0.652), heart failure (OR:2.133) and posterior circulation stroke (OR: 0.755). External validation produced an AUC of 0.726. CONCLUSIONS: The recalibrated clinical model thus obtained presented moderate-high discriminant ability and was generalisable to predict death for patients with ischaemic stroke. Rigorous external validation slightly decreased the AUC but confirmed the validity of the baseline model for the chronologically later cohort.

External Validation of SAFE Score to Predict Atrial Fibrillation Diagnosis after Ischemic Stroke: A Retrospective Multicenter Study.

Introduction: The screening for atrial fibrillation (AF) scale (SAFE score) was recently developed to provide a prediction of the diagnosis of AF after an ischemic stroke. It includes 7 items: age ≥ 65 years, bronchopathy, thyroid disease, cortical location of stroke, intracranial large vessel occlusion, NT-ProBNP ≥250 pg/mL, and left atrial enlargement. In the internal validation, a good performance was obtained, with an AUC = 0.88 (95% CI 0.84-0.91) and sensitivity and specificity of 83% and 80%, respectively, for scores ≥ 5. The aim of this study is the external validation of the SAFE score in a multicenter cohort. Methods: A retrospective multicenter study, including consecutive patients with ischemic stroke or transient ischemic attack between 2020 and 2022 with at least 24 hours of cardiac monitoring. Patients with previous AF or AF diagnosed on admission ECG were excluded. Results: Overall, 395 patients were recruited for analysis. The SAFE score obtained an AUC = 0.822 (95% CI 0.778-0.866) with a sensitivity of 87.2%, a specificity of 65.4%, a positive predictive value of 44.1%, and a negative predictive value of 94.3% for a SAFE score ≥ 5, with no significant gender differences. Calibration analysis in the external cohort showed an absence of significant differences between the observed values and those predicted by the model (Hosmer-Lemeshow's test 0.089). Conclusions: The SAFE score showed adequate discriminative ability and calibration, so its external validation is justified. Further validations in other external cohorts or specific subpopulations of stroke patients might be required.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Development of a Score to Predict the Paroxysmal Atrial Fibrillation in Stroke Patients: The Screening for Atrial Fibrillation Scale.

Background and Purpose: An individual selection of ischemic stroke patients at higher risk of atrial fibrillation (AF) might increase the diagnostic yield of prolonged cardiac monitoring and render it cost-effective. Methods: The clinical, laboratory, and brain/cardiac imaging characteristics of consecutive ischemic stroke patients without documented AF were recorded. All patients underwent at least 72 h of cardiac monitoring unless AF was diagnosed before, transthoracic echocardiogram, blood biomarkers, and intracranial vessels imaging. A predictive grading was developed by logistic regression analysis, the screening for atrial fibrillation scale (SAFE). Results: A total of 460 stroke patients were analyzed to develop the SAFE scale, a 7-items score (possible total score 0-10): age ≥ 65 years (2 points); history of chronic obstructive pulmonary disease or obstructive sleep apnea (1 point); thyroid disease (1 point); NT-proBNP ≥ 250 pg/ml (2 points); left atrial enlargement (2 points); cortical topography of stroke, including hemispheric or cerebellar cortex (1 point); and intracranial large vessel occlusion (1 point). A score = 5 identified patients with paroxysmal AF with a sensitivity of 83% and a specificity of 80%. Conclusion: Screening for atrial fibrillation scale (SAFE) is a novel and simple strategy for selecting ischemic stroke patients at higher risk of having AF who can benefit from a more thorough etiological evaluation. External validation of SAFE in a multicenter study, with a larger number of patients, is warranted.

Predictive Model and Mortality Risk Score during Admission for Ischaemic Stroke with Conservative Treatment.

BACKGROUND: Stroke is the second cause of mortality worldwide and the first in women. The aim of this study is to develop a predictive model to estimate the risk of mortality in the admission of patients who have not received reperfusion treatment. METHODS: A retrospective cohort study was conducted of a clinical-administrative database, reflecting all cases of non-reperfused ischaemic stroke admitted to Spanish hospitals during the period 2008-2012. A predictive model based on logistic regression was developed on a training cohort and later validated by the "hold-out" method. Complementary machine learning techniques were also explored. RESULTS: The resulting model had the following nine variables, all readily obtainable during initial care. Age (OR 1.069), female sex (OR 1.202), readmission (OR 2.008), hypertension (OR 0.726), diabetes (OR 1.105), atrial fibrillation (OR 1.537), dyslipidaemia (0.638), heart failure (OR 1.518) and neurological symptoms suggestive of posterior fossa involvement (OR 2.639). The predictability was moderate (AUC 0.742, 95% CI: 0.737-0.747), with good visual calibration; Pearson's chi-square test revealed non-significant calibration. An easily consulted risk score was prepared. CONCLUSIONS: It is possible to create a predictive model of mortality for patients with ischaemic stroke from which important advances can be made towards optimising the quality and efficiency of care. The model results are available within a few minutes of admission and would provide a valuable complementary resource for the neurologist.

Neurosonological Findings Related to Non-Motor Features of Parkinson's Disease: A Systematic Review.

Non-motor symptoms (NMS) in Parkinson's disease (PD), including neuropsychiatric or dysautonomic complaints, fatigue, or pain, are frequent and have a high impact on the patient's quality of life. They are often poorly recognized and inadequately treated. In the recent years, the growing awareness of NMS has favored the development of techniques that complement the clinician's diagnosis. This review provides an overview of the most important ultrasonographic findings related to the presence of various NMS. Literature research was conducted in PubMed, Scopus, and Web of Science from inception until January 2021, retrieving 23 prospective observational studies evaluating transcranial and cervical ultrasound in depression, dementia, dysautonomic symptoms, psychosis, and restless leg syndrome. Overall, the eligible articles showed good or fair quality according to the QUADAS-2 assessment. Brainstem raphe hypoechogenicity was related to the presence of depression in PD and also in depressed patients without PD, as well as to overactive bladder. Substantia nigra hyperechogenicity was frequent in patients with visual hallucinations, and larger intracranial ventricles correlated with dementia. Evaluation of the vagus nerve showed contradictory findings. The results of this systematic review demonstrated that transcranial ultrasound can be a useful complementary tool in the evaluation of NMS in PD.