Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Hyperdense middle cerebral artery sign predicts favorable outcome in patients undergoing mechanical thrombectomy.

Non-contrast computer tomography detects the presence of hyperdense middle cerebral artery sign (HMCAS). Studies on the prognostic value of HMCAS among patients undergoing mechanical thrombectomy (MT) are conflicting. A retrospective analysis of consecutive patients with acute ischemic stroke due to middle cerebral artery occlusion, presenting with or without HMCAS, who underwent MT, was performed. We enrolled 191 patients (HMCAS +, n = 140; HMCAS -, n = 51). Prevalence of successful recanalization was significantly higher in patients with HMCAS than in those without HMCAS (92.1% versus 74.5%, p = 0.001). Patients with HMCAS had a better clinical outcome than those HMCAS - (54.3% versus 37.3%, p = 0.037, for three-month favorable outcome; 62.9% versus 39.3%, p = 0.004, for major neurological improvement at discharge; 8.6% versus 19.6%, p = 0.035, for in-hospital mortality; 14.3% versus 27.5%, p = 0.035, for intracranial hemorrhage; 2.9% versus 17.6%, p = 0.001, for symptomatic intracranial hemorrhage). Multivariate analyses confirmed that HMCAS represents an independent predictor of three-month favorable outcome (OR 2.48, 95% CI 1.10-5.58, p = 0.028), major neurological improvement at discharge (OR 2.40, 95% CI 1.09-5.20, p = 0.030), in-hospital mortality (OR 0.29, 95% CI 0.010-0.81, p = 0.018), presence of ICH (OR 0.49, 95% CI 0.25-0.97, p = 0.042) and presence of SICH (OR 0.16, 95% CI 0.04-0.63, p = 0.009). HMCAS presence predicts favorable outcome in patients undergoing MT. This result may indicate that hyperdense clots are more likely to respond to MT than isodense ones. This effect is mediated by reduction in hemorrhagic transformation.

Seizures after Ischemic Stroke: A Matched Multicenter Study.

OBJECTIVE: The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. METHODS: We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. RESULTS: In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. INTERPRETATION: Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy. ANN NEUROL 2021;90:808-820.

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.

Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder.

BACKGROUND: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). OBJECTIVE: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. METHODS: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. RESULTS: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. CONCLUSION: Our results do not support a major role for variants in these genes in the risk of iRBD. © 2020 International Parkinson and Movement Disorder Society.

Prevalence of Restless Legs Syndrome in Migraine Patients: A Case-Control Study. Analysis of Risk Factors for Restless Legs Syndrome in Migraine Patients.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder. It can be idiopathic, associated to other diseases or to pharmacologic treatments. RLS has been reported to occur more frequently in migraine patients, but a clear pathogenetic link seems still under debate. We aimed to evaluate RLS prevalence in migraine, impact on sleep quality and the main clinical determinants of this association. METHODS: Migraine patients and age- and sex-matched controls were enrolled from 1st January 2011 to 30th December 2012. Migraine and RLS diagnosis complied with already published clinical criteria. Medical and pharmacological histories, as well as structured questionnaires were collected. RESULTS: RLS was found in 29/180 (16.1%) patients and 11/180 (6.1%) controls. The odds ratio (OR) for RLS was 2.95 (CI 95%, 1.42-6.11). Among migraine patients, after adjustment for possible confounding factors, familial history (OR 3.863, CI 1.076-13.873), and serotoninergic overload (OR 3.654, CI 1.347-9.916) were significantly associated with RLS occurrence. Pittsburgh Sleep Quality Index score was higher in migraine patients with RLS than in subjects without RLS. CONCLUSIONS: The confirmed association between migraine and RLS might be because of familial predisposition and to serotoninergic drugs effect, possibly interfering with the balance between dopaminergic and serotoninergic pathways.

Are Early Seizures Predictive of Epilepsy after a Stroke? Results of a Population-Based Study.

BACKGROUND: In addition to determining the cumulative incidence and risk factors for early seizures (ES), late seizures (LS) and post stroke epilepsy (PSE), we aimed at checking if ES represented a risk factor for epilepsy and if early treatment after ES prevented the occurrence of subsequent seizures. METHODS: This study was part of a 2-year prospective community-based registry of all cerebrovascular events in the district of Udine (153,312 inhabitants), North-Eastern Italy, between April 1, 2007 and March 31, 2009. People with transient ischemic attacks (TIAs) were excluded from this study. RESULTS: In all, 782 cases of stroke (79.28% ischemic, 14.83% hemorrhagic, 3.20% subarachnoid hemorrhage and 2.69% undetermined) were identified. The incidence of ES, LS and PSE was 5.10, 3.14 and 2.22%, respectively. Intracerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined origin and hyponatremia, represented risk factors for ES (p < 0.05). Among ischemic strokes, ES risk factors were hyponatremia (p = 0.024) and hemorrhagic transformation (p = 0.046). LS risk factors were younger age (p = 0.004) and cortical location of stroke (p = 0.004). Within ischemic strokes, LS risk factors were younger age (p = 0.020) and cortical location (p < 0.0001). Within intracerebral hemorrhages, the only risk factor for LS was the presence of a previous ES (p = 0.017). PSE risk factors were the same as for LS. CONCLUSIONS: All acute conditions related to the occurrence of stroke are implicated in the pathogenesis of ES, which becomes a risk factor for LS only in the setting of intracerebral hemorrhages. Therefore, early antiepileptic treatment is needed only in this situation.

Identification of stroke etiology may contribute to improve the outcome in dedicated units.

BACKGROUND: The purpose of our study is to investigate whether stroke unit (SU) care and the utilization of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria may contribute to reduce death and disability in hospitalized patients after a first-ever ischemic stroke (IS). METHODS: Data included in the present study were derived from our previous study on the incidence and outcome of cerebrovascular diseases in the district of Udine, performed from April 1, 2007, to March 31, 2009. RESULTS: We identified 429 hospitalized first-ever IS cases, 297 of 429 (69.2%) patients were admitted to a dedicated SU and 132 of 429 (30.8%) to a general medical ward. According to the TOAST criteria, 101 of 132 first-ever ISs (76.5%) admitted to general medical wards were of undetermined (UND) etiology, whereas in only 105 of 297 (35.4%) patients admitted to the SU, the diagnosis remained UND. Multivariable analysis after propensity score matching showed that compared with general medical wards, SU care was associated with a reduced probability of being dead or highly disabled (P = .025) at the end of follow-up. Moreover, patients with an UND diagnosis had a worse 6-month case fatality (P < .0001) and also higher risk of being dead or highly disabled (P < .0001). CONCLUSIONS: Our study provides real-world evidence that accurate etiologic subtype classification of ISs according to TOAST criteria and SU care as opposed to general medical ward management are associated with reduction of the proportion of poor outcomes in first-ever IS patients.

Clinical and functional determinants of appropriate rehabilitation referrals after stroke: a single-center retrospective cohort study.

BACKGROUND: Rehabilitation is currently the best available treatment for post-stroke disability. There is, however, great variability in the proportion of patients accessing rehabilitation across high-income countries suggesting that factors not explained by facilities availability or guidelines diversity may intervene in decision-making. OBJECTIVES: To evaluate which factors are associated with appropriate post-stroke rehabilitation referrals in a tertiary stroke unit setting. METHODS: Retrospective single-center cohort study including patients admitted to the Stroke Unit of the "Santa Maria della Misericordia" University Hospital, Udine (IT) from January 1st to December 31st, 2019. Information regarding stroke severity (National Institute of Health Stroke Scale), functional assessment (modified Rankin scale [mRS] and Barthel index [BI]), length of hospital stay, and rehabilitation pathway was collected. Outcome was defined as referral to the appropriate rehabilitation pathway. Appropriateness was assessed comparing patient clinical information at discharge against local criteria for intensive vs. extensive rehabilitation. A mixed-linear effect model was built to explore NIHSS, mRS, and BI variation over time. Multivariable logistic regression was used to estimate the adjusted-odds ratio (OR) and 95% confidence interval (CI 95%) of appropriate assignment to rehabilitation pathways. RESULTS: 288 patients were included in the study (age 73.1 years, males 57.9%) and in 75.7%, the rehabilitation pathway assignment was appropriate. NIHSS at discharge was lower compared to admission but no effect of rehabilitation assignment was evident, while mRS scores at discharge and at three months were 2.6 (CI 95% 2.2; 3.0) and 2.1 (CI 95% 1.8; 2.5) higher compared to admission (p < 0.0001). Rehabilitation assignment effect on mRS was time dependent, resulting in an additional - 0.6 (CI 95% - 1.0; - 0.2) lowering at discharge for those appropriately assigned (p = 0.003), with a trend for significance at three months (p = 0.08). BI score was higher at discharge (p < 0.0001), and appropriate assignment was associated with higher scores (p = 0.01). Multivariate analysis showed that the OR of appropriate rehabilitation pathway assignment were reduced by higher mRS (0.60 [CI 95% 0.48; 0.76], p < 0.0001) and increased by higher NIHSS (1.11 [CI 95% 1.04; 1.19], p = 0.001) scores at discharge. The latter finding might be explained by the rehabilitation assessment focus on post-stroke motor symptoms captured by NIHSS. CONCLUSIONS: Higher mRS and lower NIHSS levels at discharge were independent predictors for inappropriate rehabilitation assignment after stroke in our cohort. These findings may reflect a therapeutic bias toward patients with higher post-stroke disability in a rehabilitation framework heavily tilted on post-stroke motor symptoms.

Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.

Isolated insular stroke: topography is the answer with respect to outcome and cardiac involvement.

Background and purpose: Isolated insular strokes (IIS) are a rare occurrence due to the frequent concomitant involvement of adjacent territories, supplied by the M2 segment of the middle cerebral artery (MCA), and clinical aspects are sometimes contradictory. We aimed to describe clinical and radiological characteristics of a pure IIS case series, focusing on its functional outcome and cardiac involvement. Methods: We identified 15 isolated insular ischemic strokes from a pool of 563 ischemic strokes occurred between January 2020 and December 2021. Data collection consisted of demographic and baseline clinical characteristics, comorbidities, electrocardiograms, echocardiograms, stroke topography and etiology, reperfusive treatments, and outcome measures. Descriptive statistical analysis was carried out. Results: Newly detected cardiovascular alterations were the prevalent atypical presentation. Cardioembolism was the most frequent etiology. Most of patients had major neurological improvement at discharge and good outcome at 3-months follow-up. Discussion and conclusion: IIS are extremely rare, representing according to our study about 2.6% ischemic strokes cases per year, and patients have peculiar clinical manifestations, such as dysautonomia and awareness deficits. Our data suggest the possibility for these patients to completely recover after acute ischemic stroke notwithstanding the pivotal role of the insula in cerebral connections and the frequent association with MCA occlusion. Moreover, given the central role of the insula in regulating autonomic functions, newly detected cardiac arrhythmias must be taken into consideration, as well as a full diagnostic work-up for the research of cardioembolic sources. To our knowledge, this is the largest monocentric case series of IIS and it might be useful for future systematic reviews.

Stress hyperglycemia is associated with futile recanalization in patients with anterior large vessel occlusion undergoing mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) due to anterior large vessel occlusion (LVO). Despite successful recanalization, some patients remain disabled after 3 months. Mechanisms that can cause futile recanalization (FR) are still largely unknown. We investigated if stress hyperglycemia might be associated with FR. PATIENTS AND METHODS: This is a retrospective analysis of consecutive patients with successful recanalization treated in four participating centers between January 2021 and December 2022. According to the modified Rankin scale (mRS) status at 3 months, patients were divided into two groups: FR, if mRS score >2, and useful recanalization (UR), if mRS score ⩽2. Stress hyperglycemia was estimated by the glucose-to-glycated hemoglobin ratio (GAR) index. RESULTS: A total of 691 subjects were included. At 3 months, 403 patients (58.3%) were included in the FR group, while the remaining 288 patients (41.7%) were included in the UR group. At the multivariate analysis, variables independently associated with FR were the following: age (OR 1.04, 95% CI 1.02-1.06, p < 0.001), GAR index (OR 1.08, 95% CI 1.03-1.14, p = 0.003), NIHSS at admission (OR 1.16, 95% CI 1.11-1.22; p < 0.001), and procedure length (OR 1.01, 95% CI 1.00-1.02; p = 0.009). We observed that the model combining age, GAR index, NIHSS at admission, and procedure length had good predictive accuracy (AUC 0.78, 95% CI 0.74-0.81). CONCLUSIONS: Stress hyperglycemia predicts FR in patients with successful recanalization after MT. Further studies should explore if managing stress hyperglycemia may reduce futile recanalization. Additionally, we recommend paying close attention to AIS patients with a GAR index greater than 24.8 who exhibit a high risk of FR.

Post-Stroke Status Epilepticus: Time of Occurrence May Be the Difference?

(1) Background: Stroke is one of the most frequent causes of status epilepticus (SE) in adults. Patients with stroke and SE have poorer prognosis than those with stroke alone. We described characteristics and prognosis of early- and late-onset post-stroke SE (PSSE). (2) Methods: We retrospectively analyzed consecutive stroke patients who experienced a first SE between August 2012 and April 2021, comparing clinical characteristics, stroke, and SE features between early- versus late-onset SE in relation to patients' outcome. (3) Results: Forty stroke patients experienced PSSE. Fourteen developed an early-onset SE (35%) and twenty-six a late-onset SE (65%). Early-onset SE patients had a slightly higher NIHSS score at admission (6.9 vs. 6.0; p = 0.05). Early-onset SE was more severe than late-onset, according to STESS (Status Epilepticus Severity Score) (3.5 vs. 2.8; p = 0.05) and EMSE (Epidemiology-based Mortality score in Status Epilepticus) score (97.0 vs. 69.5; p = 0.04); furthermore, it had a significant impact on disability at 3-month and 1-year follow-up (p = 0.03 and p = 0.02). SE recurrence and seizures relapse were observed mainly in cases of late-onset SE. (4) Conclusions: Early-onset SE seems to be associated with higher disability in short- and long-term follow-up as possible expression of severe acute brain damage.

Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients' Plasma.

The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from three groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD-related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the only pathway altered in CTRL-related treatment. Indeed, 36 different biological processes turned out to be deregulated after PT treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients' plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease.

The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling.

Introduction: It is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are "disabling" or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS. Methods: We included all consecutive patients admitted for AIS at our institution from January 2015 to May 2022 who presented a baseline NIHSS score of 0-5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scored more than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database. Results: After the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0-1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment. Discussion: This observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS.

Stress hyperglycemia as a modifiable predictor of futile recanalization in patients undergoing mechanical thrombectomy for acute ischemic stroke.

Introduction: Mechanical thrombectomy (MT) is the first line treatment in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Approximately half of patients treated with MT does not have a favorable outcome 3 months after stroke. The aim of this study was to identify predictors of futile recanalization (FR) in patients with LVO treated with MT. Methods: A retrospective analysis of consecutive patients with acute ischemic stroke due to anterior circulation LVO who underwent MT. Patients with a TICI score of 2b or 3 were included. We distinguished two groups, FR and meaningful recanalization (MR), according to patients' disability three months after stroke (FR: mRS score > 2; MR: mRS score < 2). Results: We enrolled 238 patients (FR, n = 129, 54.2%; MR, n = 109, 45.8%). Age (OR 1.05, 95% CI 1.01-1.09, p = 0.012), female sex (OR 2.43, 95% CI 1.12-5.30, p = 0.025), stress hyperglycemia, as measured by the GAR index, (OR 1.17, 95% CI 1.06-1.29, p = 0.002), NIHSS at admission (OR 1.15, 95% CI 1.07-1.25, p = 0.001) and time from symptoms onset to MT (OR 1.01, 95% CI 1.00-1.01, p = 0.020) were independent predictors of FR. The AUC for the model combining age, female sex, GAR index, NIHSS at admission and time from symptoms onset to MT was 0.81 (95% CI 0.76-0.87; p < 0.001). The optimal GAR index cut-off score to predict FR was 17.9. Discussion: FR is common after MT. We recognized older age, female sex and baseline NIHSS as non-modifiable predictors of FR. On the other hand, time from symptoms onset to MT and stress hyperglycemia were modifiable pre- and post-MT factors, respectively. Any effort should be encouraged to reduce the impact of these modifiable predictors.

Ischemic strokes in COVID-19: risk factors, obesity paradox, and distinction between trigger and causal association.

Background and purpose: Stroke has been described as a COVID-19 complication. However, its occurrence rate, risk factors, and causal relationships are still not well established. Methods: We describe the characteristics of confirmed COVID-19-related strokes among all cases of COVID-19 hospitalized in our health network, from November 1, 2020 to April 30, 2021. Risk factor analysis has been conducted for ischemic stroke (IS), which represents 92% of all confirmed cases of Covid-19-related strokes, and a "causal attribution to infection" classification is provided. Results: In all, 62/4105 hospitalized COVID-19 patients had an acute stroke (1.51%). Severe COVID-19 (OR 2.27-CI 1.06-4.77; p = 0.032), atrial fibrillation (OR 3.65-CI 1.63-7.98; p = 0.001), and ischemic heart disease (OR 4.590-CI 1.714-12.137; p = 0.002) proved to be independent risk factors for IS, while obesity was a protective factor (OR 0.90-CI 0.82-0.97; p = 0.012). COVID-19 had a causal role in 32.1% of IS cases, was a relevant cofactor in 28.6% of cases of IS, and was a possible trigger in 39.3% of events. Conclusion: Our stroke occurrence rate is consistent with other population-based reports (range 0.34-2.7%). Prespecified peculiar clinical and radiological features allow the distinction between "IS caused by COVID-19" and "IS triggered by COVID-19." Clinical history of vascular diseases and risk factors is crucial in determining the risk of IS in patients with COVID-19. However, the protective effect of a BMI > 30 kg/m2 seems to suggest an obesity paradox.

HLA in isolated REM sleep behavior disorder and Lewy body dementia.

Background and Objectives: Isolated/idiopathic REM sleep behavior disorder (iRBD) and Lewy body dementia (LBD) are synucleinopathies that have partial genetic overlap with Parkinson's disease (PD). Previous studies have shown that neuroinflammation plays a substantial role in these disorders. In PD, specific residues of the human leukocyte antigen ( HLA ) were suggested to be associated with a protective effect. This study examined whether the HLA locus plays a similar role in iRBD, LBD and PD. Methods: We performed HLA imputation on iRBD genotyping data (1,072 patients and 9,505 controls) and LBD whole-genome sequencing (2,604 patients and 4,032 controls) using the multi-ethnic HLA reference panel v2 from the Michigan Imputation Server. Using logistic regression, we tested the association of HLA alleles, amino acids and haplotypes with disease susceptibility. We included age, sex and the top 10 principal components as covariates. We also performed an omnibus test to examine which HLA residue positions explain the most variance. Results: In iRBD, HLA-DRB1 *11:01 was the only allele passing FDR correction (OR=1.57, 95% CI=1.27-1.93, p =2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR=1.26, 95%CI=1.12-1.41, p =8.76e-05), 70Q (OR=0.81, 95% CI=0.72-0.91, p =3.65e-04) and 71R (OR=1.21, 95% CI=1.08-1.35, p =1.35e-03). In HLA-DRB1 , position 71 ( p omnibus =0.00102) and 70 ( p omnibus =0.00125) were associated with iRBD. We found no association in LBD. Discussion: This study identified an association between HLA-DRB1 11:01 and iRBD, distinct from the previously reported association in PD. Therefore, the HLA locus may play different roles across synucleinopathies. Additional studies are required better to understand HLA's role in iRBD and LBD.

NPC1 variants are not associated with Parkinson's disease, REM-sleep behavior disorder or dementia with Lewy bodies in European cohorts.

NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement-sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.