Acute ischemic STROKE - from laboratory to the Patient's BED (STROKELABED): A translational approach to reperfusion injury. Study Protocol.

Cerebral edema (CE) and hemorrhagic transformation (HT) are frequent and unpredictable events in patients with acute ischemic stroke (AIS), even when an effective vessel recanalization has been achieved. These complications, related to blood-brain barrier (BBB) disruption, remain difficult to prevent or treat and may offset the beneficial effect of recanalization, and lead to poor outcomes. The aim of this translational study is to evaluate the association of circulating and imaging biomarkers with subsequent CE and HT in stroke patients with the dual purpose of investigating possible predictors as well as molecular dynamics underpinning those events and functional outcomes. Concurrently, the preclinical study will develop a new mouse model of middle cerebral artery (MCA) occlusion and recanalization to explore BBB alterations and their potentially harmful effects on tissue. The clinical section of the study is based on a single-center observational design enrolling consecutive patients with AIS in the anterior circulation territory, treated with recanalization therapies from October 1, 2015 to May 31, 2020. The study will employ an innovative evaluation of routine CT scans: in fact, we will assess and quantify the presence of CE and HT after stroke in CT scans at 24 h, through the quantification of anatomical distortion (AD), a measure of CE and HT. We will investigate the relationship of AD and several blood biomarkers of inflammation and extracellular matrix, with functional outcomes at 3 months. In parallel, we will employ a newly developed mouse model of stroke and recanalization, to investigate the emergence of BBB changes 24 h after the stroke onset. The close interaction between clinical and preclinical research can enhance our understanding of findings from each branch of research, enabling a deeper interpretation of the underlying mechanisms of reperfusion injury following recanalization treatment for AIS.

The Role of Double Interatrial Septum in Cryptogenic Stroke.

In this work, the case of a 70-year-old Caucasian woman affected by cryptogenic stroke is reported. After discarding other sources of embolism, a transesophageal echocardiogram was performed, which revealed the presence of a double interatrial septum associated with a left-sided atrial pouch. The persistent interatrial space was identified as the most probable source of thrombus.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

Quality control in treating patients with patent foramen ovale: 7-year-experience of the Heart and Brain team of the Careggi University Hospital.

BACKGROUND: The right comprehension of ischemic stroke pathogenesis guarantees the best prevention therapy. The term "patent foramen ovale (PFO) related stroke" has been proposed for those events where PFO is supposed to be pathogenetic, but their definition is challenging. A multidisciplinary evaluation in a "Heart & Brain" team (HBteam) including stroke neurologists and interventional cardiologists was therefore highly recommended in the recent guidelines of secondary stroke prevention. OBJECTIVE: We aimed at describing the organization of the HBteam of Careggi-University-Hospital of Florence (Italy), and the results of the first seven years of activity. METHODS: In 2016 Interventional Cardiologists and Stroke Neurologists set up an outpatient clinic for the joined evaluation of patients with PFO and other cardio/neurological conditions. A specific diagnostic-therapeutic hospital plan was produced for PFO patients. Patient empowerment was guaranteed by a hospital explicative webpage, a booklet regarding risks/benefits of PFO closure and a 3D heartmodel to simulate the intervention. Data were collected in a dedicated registry. RESULTS: We evaluated 594 patients for PFO, 40 for left atrial appendage closure and 38 for other conditions. In 20% of PFO-patients, HBteam diagnosis was discordant from that of referring physicians, 14% were stroke misdiagnoses. We advised against closure in 53% of patients. At follow-up 94% of closed patients had no/minimum residual shunt; 3 patients had a cerebral ischemic event. CONCLUSIONS: A dedicated HBteam represents a unique opportunity to share decisions with patients after a thorough empowerment process. The joining of cardioneurological skills allows a better classification of PFO-patients, reducing futile interventions.

Determinants of cerebral collateral circulation in acute ischemic stroke due to large vessel occlusion.

Introduction: Cerebral collateral circulation has a central role in ischemic stroke pathophysiology, and it is considered to correlate with infarct size, the success of reperfusion therapies, and clinical outcomes. Our aim was to study the factors influencing the development of collaterals in patients with acute ischemic stroke eligible for endovascular treatment. Materials and methods: We enrolled patients with acute ischemic stroke and large vessel occlusion of anterior circulation potentially eligible for endovascular treatment. Included patients performed multiphase CT angiography to assess collaterals that were graded by the Menon Grading Score. We investigated the associations between clinical factors and collaterals and tested independent associations with logistic (good vs. poor collaterals) and ordinal (collateral grade grouped, Menon 0-2, 3, 4-5) regression analysis adjusting for age, sex, stroke severity, and onset to CT time (OCTT). Results: We included 520 patients, the mean age was 75 (±13.6) years, 215 (41%) were men, and the median (IQR) NIHSS was 17 (11-22). Good collaterals were present in 323 (62%) patients and were associated with lower NIHSS (median 16 vs. 18; p < 0.001) and left hemisphere involvement (60% vs. 45%; p < 0.001), whereas previous stroke/TIA was more frequent in patients with poor collaterals (17 vs. 26%; p = 0.014). These results were confirmed in both logistic and ordinal regression analyses where good collaterals were associated with lower NIHSS (OR = 0.94; 95% CI = 0.91-0.96; cOR = 0.95; 95% CI = 0.92-0.97, respectively) and left hemisphere stroke (OR = 2.24; 95% CI = 1.52-3.28; cOR = 2.11; 95% CI = 1.46-3.05, respectively), while previous stroke/TIA was associated with poor collaterals (OR = 0.57; 95% CI = 0.36-0.90; cOR = 0.61; 95% CI = 0.40-0.94, respectively). Vascular risk factors, demographics, and pre-stroke treatments did not influence the collateral score. Discussion: The results of our study suggest that risk factors and demographics do not influence the development of collateral circles, except for a negative relation with previous ischemic events. We confirm an already reported observation of a possible protective effect of collaterals on tissue damage assuming NIHSS as its surrogate. The association between left hemispheric stroke and better collaterals deserves to be further explored. Further efforts are needed to identify the factors that favor the development of collaterals.

Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Metabolic perturbations and inflammatory mediators play a fundamental role in both early and late adverse post-acute ischemic stroke outcomes. Using data from the observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) study, we evaluated the effect of 130 serum metabolic features, using a nuclear magnetic spectroscopy approach, on the following outcomes: hemorrhagic transformation at 24 h after stroke, non-response to intravenous thrombolytic treatment with the recombinant tissue plasminogen activator (rt-PA), and the 3 month functional outcome. Blood circulating metabolites, lipoproteins, and inflammatory markers were assessed at the baseline and 24 h after rt-PA treatment. Adjusting for the major determinants for unfavorable outcomes (i.e., age, sex, time onset-to-treatment, etc.), we found that acetone and 3-hydroxybutyrate were associated with symptomatic hemorrhagic transformation and with non-response to rt-PA; while 24 h after rt-PA, levels of triglycerides high-density lipoprotein (HDL) and triglycerides low-density lipoprotein (LDL) were associated with 3 month mortality. Cholesterol and phospholipids levels, mainly related to smaller and denser very low-density lipoprotein (VLDL) and LDL subfractions were associated with 3 month poor functional outcomes. We also reported associations between baseline 24 h relative variation (Δ) in VLDL subfractions and ΔC-reactive protein, Δinterleukin-10 levels with hemorrhagic transformation. All observed metabolic changes reflect a general condition of energy failure, oxidative stress, and systemic inflammation that characterize the development of adverse outcomes.

Endovascular treatment in patients with acute ischemic stroke and cancer: Systematic review and meta-analysis.

Introduction: Although stroke occurs frequently in patients with cancer, there is scarce evidence regarding the safety and efficacy of endovascular treatment (EVT) in patients with acute ischemic stroke and concurrent cancer. We performed a systematic review and meta-analysis to summarize the existing literature. Methods: We searched for English written observational studies reporting data on safety and efficacy of EVT in patients with acute ischemic stroke and concurrent cancer. Outcomes of interest were: functional independence (modified Rankin Scale (mRS) ⩽ 2); mortality at 3 months; rate of successful recanalization (modified Treatment In Cerebral Ischemia (mTICI) 2b or 3); occurrence of any hemorrhagic transformation (both symptomatic and asymptomatic). We pooled data with Maentel-Haenszel model to calculate cumulative odds ratios (ORs). Results: We included seven studies with a total of 4465 patients, of whom 262 (6%) with cancer. We observed various definitions of cancer across included studies. Patients with cancer had less likely mRS⩽2 at 3 months (24% vs 42%, OR = 0.44; 95% CI = 0.32-0.60) and increased probability of death (43% vs 19%, OR = 5.02; 95% CI = 2.90-8.69). There was no difference in successful recanalization (70% vs 75%, OR = 0.84; 95% CI = 0.49-1.44); patients with cancer had increased risk of any intracerebral hemorrhage after treatment (49% vs 34%, OR = 1.95; 95% CI = 1.28-2.96), though not for symptomatic ICH (OR 1.04; 95% CI = 0.59-1.85). Conclusion: Patients with acute ischemic stroke and cancer have similar EVT recanalization but higher probability of functional dependence, death, and any hemorrhagic transformation, though not necessarily symptomatic, compared with patients without cancer. Our results may help communication with patients and carers.

Can CHA2DS2-VASc and HAS-BLED Foresee the Presence of Cerebral Microbleeds, Lacunar and Non-Lacunar Infarcts in Elderly Patients With Atrial Fibrillation? Data From Strat-AF Study.

Anticoagulants reduce embolic risk in atrial fibrillation (AF), despite increasing hemorrhagic risk. In this context, validity of congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke, vascular disease, age 65-74 years and sex category (CHA2DS2-VASc) and hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly (HAS-BLED) scales, used to respectively evaluate thrombotic and hemorrhagic risks, is incomplete. In patients with AF, brain MRI has led to the increased detection of "asymptomatic" brain changes, particularly those related to small vessel disease, which also represent the pathologic substrate of intracranial hemorrhage, and silent brain infarcts, which are considered risk factors for ischemic stroke. Routine brain MRI in asymptomatic patients with AF is not yet recommended. Our aim was to test predictive ability of risk stratification scales on the presence of cerebral microbleeds, lacunar, and non-lacunar infarcts in 170 elderly patients with AF on oral anticoagulants. Ad hoc developed R algorithms were used to evaluate CHA2DS2-VASc and HAS-BLED sensitivity and specificity on the prediction of cerebrovascular lesions: (1) Maintaining original items' weights; (2) augmenting weights' range; (3) adding cognitive, motor, and depressive scores. Accuracy was poor for each outcome considering both scales either in phase 1 or phase 2. Accuracy was never improved by the addition of cognitive scores. The addition of motor and depressive scores to CHA2DS2-VASc improved accuracy for non-lacunar infarcts (sensitivity = 0.70, specificity = 0.85), and sensitivity for lacunar-infarcts (sensitivity = 0.74, specificity = 0.61). Our results are a very first step toward the attempt to identify those elderly patients with AF who would benefit most from brain MRI in risk stratification.

Association between carotid artery dissection and vascular tortuosity: a case-control study.

PURPOSE: We aimed to verify if vascular tortuosity (VT) may represent a risk factor for spontaneous epiaortic vessel dissection (sEVD) in young adult patients. METHODS: We identified 304 patients aged under 55 years consecutively admitted for acute cerebrovascular events to our Stroke Unit. After checking the possibility to perform a 3D reconstruction of epiaortic vessels on CT-angiography images, we selected and compared fifty patients with sEVD (cases) with fifty-one patients without dissection (controls). VT of carotid and vertebral arteries was measured on reconstructions evaluating the vascular tortuosity index (VTI), calculated according to a specific algorithm, and the presence of kinking and coiling. Differences between groups were analyzed by Student-t test for numeric variables and chi-square test for categoric ones. A ROC curve analysis was used to look for a VTI threshold value beyond which the risk of dissection was significantly increased. RESULTS: VTI was significantly higher in cases than in controls only considering carotid arteries (p = 0.029); cases did not have a significantly higher rate of kinking and coiling than controls (p = 0.059 and 0.077, respectively). We have found a significant VTI threshold value of 27.9% (under curve area = 61.6%, p = 0.04) only for carotid artery dissection. CONCLUSION: VT appears to be associated with an increased risk of dissection for the carotid district but not for the vertebral one. The different structure, embryogenesis, and pathophysiology of dissection between the two districts could explain this finding. VTI threshold as carotid artery dissection predictor deserves confirmation in larger studies.

Fabry-Stroke Italian Registry (FSIR): a nationwide, prospective, observational study about incidence and characteristics of Fabry-related stroke in young-adults. Presentation of the study protocol.

BACKGROUND: TIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician's attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry's stroke are scanty. METHODS: The study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event. DISCUSSION: The potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke.

Relation between the size of patent foramen ovale and the volume of acute cerebral ischemic lesion in young patients with cryptogenic ischemic stroke.

BACKGROUND: Patent foramen ovale (PFO) closure is superior to medical therapy alone to prevent stroke recurrence in selected patients. Small cortical infarcts and large right to left shunts seem to identify patients who will benefit most from closure. We aimed to study the correlation between the size of the PFO and the volume of cerebral ischemic lesions in young patients with cryptogenic ischemic stroke. METHODS: PFO dimensions and acute ischemic lesion volume of 20 patients, aged<55 years, were analyzed with transesophageal echocardiography and brain magnetic resonance imaging, respectively. The association between the volume of ischemic lesions with the length of PFO, maximum separation between septum primum and septum secundum, and the combination of the twos was explored. RESULTS: A direct statistically significant correlation was found between cerebral lesion volume and maximum separation of septum primum and septum secundum (p=0.047). Length of PFO showed a non-significant trend towards an inverse correlation with lesion volume (p=0.603). Multiple linear regression analysis showed that cerebral lesion volume was dependent directly on maximum separation and inversely on length of PFO (regression coeff. -0,837; p= 0.057; 2,536, p=0.006, respectively). CONCLUSIONS: These data suggest that even small PFO might be pathogenetic in case of small cerebral infarcts and that large cerebral infarcts might be PFO related if the shunt is large. If confirmed, the combination of detailed characteristics of PFO with the volume of cerebral infarct could be integrated in a new score to select patients who would take real advantage from a percutaneous closure.

Translational Stroke Research Review: Using the Mouse to Model Human Futile Recanalization and Reperfusion Injury in Ischemic Brain Tissue.

The approach to reperfusion therapies in stroke patients is rapidly evolving, but there is still no explanation why a substantial proportion of patients have a poor clinical prognosis despite successful flow restoration. This issue of futile recanalization is explained here by three clinical cases, which, despite complete recanalization, have very different outcomes. Preclinical research is particularly suited to characterize the highly dynamic changes in acute ischemic stroke and identify potential treatment targets useful for clinical translation. This review surveys the efforts taken so far to achieve mouse models capable of investigating the neurovascular underpinnings of futile recanalization. We highlight the translational potential of targeting tissue reperfusion in fully recanalized mouse models and of investigating the underlying pathophysiological mechanisms from subcellular to tissue scale. We suggest that stroke preclinical research should increasingly drive forward a continuous and circular dialogue with clinical research. When the preclinical and the clinical stroke research are consistent, translational success will follow.

Analysis of Metabolite and Lipid Association Networks Reveals Molecular Mechanisms Associated with 3-Month Mortality and Poor Functional Outcomes in Patients with Acute Ischemic Stroke after Thrombolytic Treatment with Recombinant Tissue Plasminogen Activator.

Here, we present an integrated multivariate, univariate, network reconstruction and differential analysis of metabolite-metabolite and metabolite-lipid association networks built from an array of 18 serum metabolites and 110 lipids identified and quantified through nuclear magnetic resonance spectroscopy in a cohort of 248 patients, of which 22 died and 82 developed a poor functional outcome within 3 months from acute ischemic stroke (AIS) treated with intravenous recombinant tissue plasminogen activator. We explored differences in metabolite and lipid connectivity of patients who did not develop a poor outcome and who survived the ischemic stroke from the related opposite conditions. We report statistically significant differences in the connectivity patterns of both low- and high-molecular-weight metabolites, implying underlying variations in the metabolic pathway involving leucine, glycine, glutamine, tyrosine, phenylalanine, citric, lactic, and acetic acids, ketone bodies, and different lipids, thus characterizing patients' outcomes. Our results evidence the promising and powerful role of the metabolite-metabolite and metabolite-lipid association networks in investigating molecular mechanisms underlying AIS patient's outcome.

Blood-brain barrier leakage and hemorrhagic transformation: The Reperfusion Injury in Ischemic StroKe (RISK) study.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke treated with reperfusion therapy we aimed to evaluate whether pretreatment blood-brain barrier (BBB) leakage is associated with subsequent hemorrhagic transformation (HT). METHODS: We prospectively screened patients with acute ischemic stroke treated with intravenous thrombolysis and/or endovascular treatment. Before treatment, each patient received computed tomography (CT), CT angiography, and CT perfusion. We assessed pretreatment BBB leakage within the ischemic area using the volume transfer constant (Ktrans ) value. Our primary outcome was relevant HT, defined as hemorrhagic infarction type 2 or parenchymal hemorrhage type 1 or 2. We evaluated independent associations between BBB leakage and HT using logistic regression, adjusting for age, sex, baseline stroke severity, Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6, treatment type, and onset-to-treatment time. RESULTS: We enrolled 171 patients with available assessment of BBB leakage. The patients' mean (±SD) age was 75.5 (±11.8) years, 86 (50%) were men, and the median (interquartile range) National Institutes of Health Stroke Scale score was 18 (12-23). A total of 32 patients (18%) received intravenous thrombolysis, 102 (60%) underwent direct endovascular treatment, and 37 (22%) underwent both. Patients with relevant HT (N = 31;18%) had greater mean BBB leakage (Ktrans 0.77 vs. 0.60; p = 0.027). After adjustment in the logistic regression model, we found that BBB leakage was associated both with a more than twofold risk of relevant HT (odds ratio [OR] 2.50; 95% confidence interval [CI] 1.03-6.03 per Ktrans point increase; OR 2.34; 95% CI 1.06-5.17 for Ktrans values > 0.63 [mean BBB leakage value]) and with symptomatic intracerebral hemorrhage (OR 4.30; 95% CI 1.13-13.77 per Ktrans point increase). CONCLUSION: Pretreatment BBB leakage before reperfusion therapy was associated with HT, and may help to identify patients at risk of HT.

Atrial Fibrillation and Resistant Stroke: Does Left Atrial Appendage Morphology Matter? A Case Report.

Introduction: Patients with atrial fibrillation (AF) can experience ischemic stroke despite adequate anticoagulant therapy. The secondary prevention strategy of these so-called "resistant strokes" is empirical. Since about 90% of patients with ischemic stroke due to atrial fibrillation have thrombus in left atrial appendage (LAA) we sought to explore the possibility that resistant stroke could have a LAA morphology resistant to anticoagulants. Case Report: A 77 years old man affected by AF experienced two cardioembolic ischemic stroke while on anticoagulants. The study of LAA showed a windsock-like morphology in the proximal part while distally the LAA presented a cauliflower morphology with a large amount of pectinate muscles and blood stagnation. The precise characteristics of LAA were properly understood integrating images obtained by cardiac CT, transesophageal echocardiography, and selective angiography. A high risky LAA for thrombus formation was diagnosed and its occlusion (LAAO) as an add-on therapy to anticoagulants was proposed and performed. Six month follow-up was uneventfully. Conclusion: The systematic study of LAA in patients with resistant-stroke could help to identify LAA malignant morphology. The efficacy on stroke recurrence of the combined therapy (anticoagulants plus LAAO) is worthy to be tested in randomized trials.

Association Between Motor and Cognitive Performances in Elderly With Atrial Fibrillation: Strat-AF Study.

Background/Objective: Growing evidence suggests a close relationship between motor and cognitive abilities, but possible common underlying mechanisms are not well-established. Atrial fibrillation (AF) is associated with reduced physical performance and increased risk of cognitive decline. The study aimed to assess in a cohort of elderly AF patients: (1) the association between motor and cognitive performances, and (2) the influence and potential mediating role of cerebral lesions burden. Design: Strat-AF is a prospective, observational study investigating biological markers for cerebral bleeding risk stratification in AF patients on oral anticoagulants. Baseline cross-sectional data are presented here. Setting: Thrombosis outpatient clinic (Careggi University Hospital). Participants: One-hundred and seventy patients (mean age 77.7 ± 6.8; females 35%). Measurements: Baseline protocol included: neuropsychological battery, motor assessment [Short Physical Performance Battery (SPPB), and walking speed], and brain magnetic resonance imaging (MRI) used for the visual assessment of white matter hyperintensities, lacunar and non-lacunar infarcts, cerebral microbleeds, and global cortical and medial temporal atrophies. Results: Mean Montreal Cognitive Assessment (MoCA) total score was 21.9 ± 3.9, SPPB total score 9.5 ± 2.2, and walking speed 0.9 ± 0.2. In univariate analyses, both SPPB and walking speed were significantly associated with MoCA (r = 0.359, r = 0.372, respectively), visual search (r = 0.361, r = 0.322), Stroop (r = -0.272, r = -0.263), short story (r = 0.263, r = 0.310), and semantic fluency (r = 0.311, r = 0.360). In multivariate models adjusted for demographics, heart failure, physical activity, and either stroke history (Model 1) or neuroimaging markers (Model 2), both SPPB and walking speed were confirmed significantly associated with MoCA (Model 1: ß = 0.256, ß = 0.236; Model 2: ß = 0.276, ß = 0.272, respectively), visual search (Model 1: ß = 0.350, ß = 0.313; Model 2: ß = 0.344, ß = 0.307), semantic fluency (Model 1: ß = 0.223, ß = 0.261), and short story (Model 2: ß = 0.245, ß = 0.273). Conclusions: In our cohort of elderly AF patients, a direct association between motor and cognitive functions consistently recurred using different evaluation of the performances, without an evident mediating role of cerebral lesions burden.

Correction to: "When should primary angiitis of the central nervous system (PACNS) be suspected?": literature review and proposal of a preliminary screening algorithm.

The above article was published online with inverted given and family names. The correct presentation has been corrected above. The original article has been corrected.