Concurrent subarachnoid haemorrhage and internal carotid artery dissection: a transcranial colour-coded sonography diagnosis.

We report the case of a young woman affected by an aneurysmal subarachnoid haemorrhage (SAH) and numerous anatomic abnormalities. A Transcranial Colour-Coded Duplex Sonography, performed with the aim of monitoring the vasospasm, showed a non-pulsatile flow with loss of sharp systolic peak and lowering of mean flow velocities in the right extracranial Internal Carotid Artery (ICA) and all its intra-cranial branches. This event suggested a possible concomitant acute right ICA sub-occlusion with a lack of collateral circulation. This type of flow is typically found in systemic and brain arteries of patients undergoing to venous-arterial extracorporeal membrane oxygenation or to left ventricular assist devices. The absence of an adequate cerebral collateral circulation might be the explanation for this type of atypical flow. Aneurysms and arterial dissections contribute to SAH and ischemic stroke events, leading to long-term physical and cognitive disability. In our case, the prompt neurosonological diagnosis leaded to patient's good outcome.

Markers of Atrial Cardiopathy in Severe Embolic Strokes of Undetermined Source.

Background and Purpose: The current definition of embolic strokes of undetermined source (ESUS) seems to be too broad, including strokes due to heterogeneous mechanisms, such as atrial cardiopathy and other occult cardiac conditions, aortic arch plaques, and non-stenosing atherosclerosis, that can be differently associated with clinical stroke severity at the time of presentation. The aim of our study was to assess the possible association between neurological deficit severity and presence of markers of atrial cardiopathy in ESUS. Methods: We retrospectively reviewed the medical records of a cohort of 226 ESUS patients (105 M, 121 F), that were divided into two groups according to the severity of neurological deficit (99 mild strokes with NIHSS ≤ 5 and 127 severe strokes with NIHSS >5). The following indices of atrial cardiopathy were evaluated: P wave dispersion, P wave max, P wave min, P wave mean, P wave index, P wave axis, left atrial size. Results: Patients with severe ESUS were significantly older (74 ± 12 vs. 67 ± 14 years, P < 0.001) and female sex was prevalent (67 vs. 36%, P > 0.001); they had higher values of P-wave-dispersion (51 ± 14 vs. 46 ± 13, P = 0.01), P-wave-max (131 ± 20 vs. 125 ± 15 ms, P = 0.01), P-wave-index (16 ± 5 vs. 15 ± 5 ms, P = 0.01), left atrial size (20 ± 6 vs. 18 ± 4 cm2, P = 0.01), left atrial volume index (31 ± 14 vs. 27 ± 11 ml/m2, P = 0.04), in comparison with mild ESUS. An abnormal P wave axis was detected more frequently in severe ESUS (21 vs. 9%, P = 0.01). Furthermore, multivariate logistic regression showed that age (OR = 1.21 for each 5-year increase, 95% CI 1.09-1.35), sex (OR = 3.24 for female sex, 95% CI 1.82-5.76) and PWD (OR = 1.32 for each 10-ms increase, 95% CI 1.07-1.64) were the best subset of associated variables for severe ESUS. Conclusions: Our findings shed light on specific clinical characteristics of severe ESUS including the presence of atrial cardiopathy that could play a pathogenic role in this subgroup of patients. Searching for atrial fibrillation in these patients is especially important to perform the most appropriate therapy.

Safety of Intravenous Thrombolysis and Mechanical Thrombectomy in Bilateral Posterior Cerebral Artery Territory Infarction.

BACKGROUND: Acute bilateral blindness is an uncommon phenomenon that requires immediate diagnosis and action. The emergent evaluation should concentrate on an early distinction between ocular, cortical, and psychogenic etiologies. OBJECTIVE: To present a case of cortical blindness without anosognosia due to the embolic occlusion of both posterior cerebral arteries (PCAs) and treated by intravenous and mechanical thrombolysis. CASE REPORT: A 67-year-old woman was admitted to the Stroke Unit due to cortical blindness without anosognosia. At the admission to the hospital, an emergent computed tomography scan of the brain ruled out intracranial acute hemorrhage and showed subtle changes consistent with hyperacute ischemia of the left occipital cortex, while a CT angiography demonstrated the occlusion of the P3 segment of both right and left posterior cerebral arteries. The patient was treated with combined thrombolysis (intravenous and mechanical thrombolysis), obtaining complete revascularization and a significant clinical improvement. CONCLUSION: Even if there is no randomized controlled trial to compare the effectiveness and safety of mechanical thrombectomy (MT) to intravenous thrombolysis in patients with posterior circulation occlusion, the good outcome of this case encourages combined stroke treatments in posterior circulation stroke, even in case of mild but disabling neurological deficits.

Outcome After Acute Ischemic Stroke Treatment During Covid-19 Outbreak in South-East Tuscany.

BACKGROUND: During Covid-19 pandemic, the Italian National Healthcare Service has faced increasing pressure, especially in Northern Italy. Even in less-affected regions, such as Tuscany, the changes in the healthcare system to prevent Covid-19 spread resulted in difficulty in treating time-dependent disorders like ischemic stroke rapidly. OBJECTIVE: The aim of our study was to assess the outcome after acute ischemic stroke treatments during the Covid-19 spread in comparison with a similar period of the previous year in Siena-Hospital (Hub center in the South-East Tuscany). METHODS: We enrolled all patients admitted to Siena-Hospital for ischemic stroke and submitted them to acute treatments (intravenous and/or mechanical thrombolysis) between February 21st and May 18th, 2020 (study group, n:38) and compared the results with ischemic strokes acutely treated in a similar period in 2019 (control group, n:39). The modified Rankin scale score was assessed at 90 days to evaluate a 3-month clinical outcome. RESULTS: In the study group, the time from symptoms onset to hospital arrival and the door-to-groin puncture time were significantly more prolonged than in the control group. In moderate-severe strokes, the 3-month mortality was significantly higher in the study group (31% vs. 6%; p=0.01), and the number of patients with poor functional outcomes was significantly higher in the study group (73% vs. 44%; p=0.03). CONCLUSION: During the lockdown period due to Covid-19 pandemic, patients with acute ischemic stroke had a worse prognosis. These findings suggest the need to improve the health system organization to guarantee an appropriate treatment during the pandemic, including the patients that are not affected by Covid-19.

Age-dependent effect of susceptibility factors on the risk of intracerebral haemorrhage: Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy).

OBJECTIVE: To investigate the age-dependent impact of traditional stroke risk factors on the occurrence of intracerebral haemorrhage (ICH). METHODS: We performed a case-control analysis, comparing consecutive patients with ICH with age-matched and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) between 2002 and 2014 by multivariable logistic regression model within subgroups stratified by age quartiles (Q1-Q4). RESULTS: We analysed 3492 patients and 3492 controls. The impact of untreated hypertension on the risk of ICH was higher in the lower than in the upper age quartile (OR 11.64, 95% CI 7.68 to 17.63 in Q1 vs OR 6.05, 95% CI 3.09 to 11.85 in Q4 with intermediate ORs in Q2 and Q3), while the opposite trend was observed for untreated hypercholesterolaemia (OR 0.63, 95% CI 0.45 to 0.97 in Q1 vs OR 0.36, 95% CI 0.26 to 0.56 in Q4 with intermediate ORs in Q2 and Q3). The effect of untreated diabetes and excessive alcohol intake was detected only in the older age group (OR 3.63, 95% CI 1.22 to 10.73, and OR 1.69, 95% CI 1.13 to 2.51, respectively). CONCLUSIONS: Our findings provide evidence of age-dependent differences in the effects of susceptibility factors on the risk of ICH.

Increased Arterial Stiffness is a Predictor of Delayed Ischaemic Stroke After Subarachnoid Haemorrhage.

BACKGROUND: Subarachnoid haemorrhage (SAH) accounts for 5-10% of strokes and its prognosis may be influenced by different complications, including delayed cerebral ischaemia (DCI). The pathophysiology of DCI is complex and still unknown. Many different mechanisms may contribute to the occurrence of DCI. Arterial stiffness (AS), a well-known risk factor for cardiovascular events, also associated with the development and rupture of cerebral aneurysms, may represent a novel contributing risk factor. The aim of our study was to investigate a possible link between AS and DCI after SAH. METHOD: Fifty-nine (59) patients with SAH (age [mean±standard deviation], 62±12 years) underwent neuroimaging examination, and 24-hour heart rate and blood pressure monitoring, including AS index (ASI) measurement. RESULTS: Of 59 patients, DCI occurred in 12. ASI was significantly higher in patients with DCI than in patients without it (0.70±0.1 vs 0.62±0.1; p=0.03). ASI was a significant predictor for DCI (odds ratio [for an increase of 0.20 points in ASI], 5.99; 95% confidence interval, 1.23-29.22; p=0.03). CONCLUSIONS: Arterial stiffness index is a simple and inexpensive tool that is able to predict the risk of DCI in patients with SAH. This marker can impact on intensive care unit monitoring, early recognition, and treatment, contributing to optimal acute management of patients with SAH.

PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis.

BACKGROUND: In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH). METHODS: Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo. RESULTS: PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29-2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03-2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43-1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17-1.60), and in mortality (OR 0.85; 95% CI 0.64-1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31-3.04). CONCLUSIONS: In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.

Non-stenosing Carotid Atherosclerosis and Arterial Stiffness in Embolic Stroke of Undetermined Source.

Background and Purpose: Recent findings suggested that non-stenosing atherosclerosis (NSA) may play an important pathogenic role, especially in cryptogenic strokes. Furthermore, arterial stiffness has been suggested to be a useful tool in identifying patients with embolic stroke of undetermined source (ESUS) with poor neurological prognosis. In this view, the aim of our study was to assess the association between carotid NSA and arterial stiffness in ESUS patients, in order to better define the cardiovascular risk profile of this subgroup of patients. Methods: We enrolled 100 patients with ESUS (52 males, 48 females) and 48 patients with ischemic stroke from atherosclerosis. All patients underwent clinical and neuroimaging examination. A 24-h heart rate and blood pressure monitoring was performed in order to evaluate systolic, diastolic and mean blood pressure, pulse pressure, and arterial stiffness index (ASI). Results: NSA was present in 48 patients. In comparison with non-NSA-ESUS, in NSA-ESUS the mean age was higher, neurological deficit was more severe, hypertension, and diabetes were more common; systolic blood pressure, pulse pressure, and ASI were higher. In particular NSA-ESUS had ASI levels similar to strokes due to atherosclerosis. Conclusions: Our findings shed light on specific cardiovascular risk profiles underlying different subtypes of ESUS, suggesting the presence of increased arterial stiffness in NSA-ESUS patients with a risk factors profile similar to strokes due to atherosclerosis.

Safety of Anticoagulation in Patients Treated With Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation.

BACKGROUND AND PURPOSE: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. METHODS: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. RESULTS: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). CONCLUSIONS: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant.

Appropriateness, safety, and effectiveness of "drip and ship" teleconsultation model in Southeastern Tuscany: a feasibility study.

PURPOSE: Teleconsultation is a consultation between two or more physicians about the diagnostic work-up and therapeutic strategy in the treatment of an individual case by means of modern telematics. 'Drip-and-ship' teleconsultation model consists of the transfer of patients, through telematics stroke networks, with large arteries occlusions from primary to comprehensive stroke centers equipped for endovascular therapy. We retrospectively investigated appropriateness, safety, and effectiveness of 'drip-and-ship' teleconsultation model in a rural area of Tuscany. METHODS: Outcome measures were: door-to-ship time (including door-to-needle time), ratio of number treated/total sent patients, adverse events/mortality during transfer, and mortality and modified Rankin scale at 90 days. Analysis of non-treated patients was also done. RESULTS: Seventy-eight patients were included; 16/78 patients were sent for endovascular therapy alone, and 62/78 for "drip-and-ship"; 12 patients were not treated. Door-to-ship, and door-to-needle times (mean ± SD) were 105 ± 29.8 and 62.5 ± 37.5 min, respectively. The ratio number of treated/total sent patients was 0.85. At 90 days, the global mortality rate was 21%, and 40% of patients showed favorable outcome. The main cause of non-treatment was spontaneous recanalization. CONCLUSIONS: The high value for treated/total sent patients' ratio underlines that "drip-and-ship" teleconsultation model is appropriate and effective, with a few untreated patients. The model is safe, without adverse events during transfer. Taken together, our outcomes are in line with the previous reports. "Drip-and-ship" teleconsultation model is safe and effective in rural areas, allowing good selections and rapid treatments for stroke patients, based on the transfer from the primary to the comprehensive stroke center.

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

INTRODUCTION: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. MATERIALS AND METHODS: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. RESULTS: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). DISCUSSION: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. CONCLUSIONS: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Anticoagulation After Stroke in Patients With Atrial Fibrillation.

Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.

BACKGROUND: The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. PURPOSE: In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. METHODS: In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. RESULTS: A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)). CONCLUSIONS: After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

P Wave Dispersion and Silent Atrial Fibrillation in Cryptogenic Stroke: The Pathogenic Role of Inflammation.

BACKGROUND: Cryptogenic stroke (CS) represents 25% of ischemic strokes. Especially after CS, the detection of atrial fibrillation (AF) is important because it provides clues to the mechanism of stroke. However, the relationship between AF and stroke appears more complex than a simple cause-effect mechanism, suggesting that the association between AF and stroke may be due to other systemic and atrial factors including systemic inflammation that may lead to atrial remodeling and subsequent atrial cardiopathy. OBJECTIVE: The aim of this study was to evaluate the relationship among different electrocardiographic parameters, inflammatory markers and in-hospital AF occurrence after acute CS. METHODS: 222 patients with CS underwent 12-lead resting ECG at admission and 7-day in-hospital ECG monitoring. The following indices were evaluated: P-wave dispersion (PWD), P-wave index, P-wave axis, atrial size and high-sensitivity-C reactive protein (CRP). RESULTS: AF was detected in 44 patients. AF-group had significantly higher PWD, P-wave index, PR interval, CRP and greater frequency of abnormal P-wave axis in comparison with no-AF group. There was a significant correlation between CRP and PWD (r=0.28). By using the mediation analysis, performed according to the "bootstrapping" method, we found that PWD is a significant mediator variable of the relationship between CRP and AF occurrence, accounting for 40% of the association. CONCLUSIONS: In cryptogenic stroke, high PWD is partly due to systemic inflammation that increases AF risk possibly via atrial electric remodeling. These findings could also suggest inflammation as a possible therapeutic target in order to prevent atrial electrical alterations and finally AF occurrence in CS.

An Ig Transmembrane Domain Motif Improves the Function of TCRs Transduced in Human T Cells: Implications for Immunotherapy.

Adoptive transfer of T lymphocytes (ACT) engineered with T-cell receptors (TCRs) of known antitumor specificity is an effective therapeutic strategy. However, a major constraint of ACT is the unpredictable interference of the endogenous TCR α and ß chains in pairing of the transduced TCR. This effect reduces the efficacy of the genetically modified primary T cells and carries the risk of generating novel TCR reactivities with unintended functional consequences. Here, we show a powerful approach to overcome these limitations. We engineered TCR α and ß chains with mutations encompassing a conserved motif (FXXXFXXS) required to stabilize the pairing of immunoglobulin heavy chain transmembrane domains. Molecular modeling supported the preferential pairing of mutated TCR and impaired pairing between mutated and wild-type TCRs. Expression of the mutated TCR was similar to wild type and conferred the expected specificity. Fluorescence resonance energy transfer analysis in mouse splenocytes transduced with mutated or wild-type TCRs showed a higher proximity of the former over the latter. Importantly, we show that mutated TCRs effectively outcompete endogenous TCRs and improve in vitro antitumor cytotoxicity when expressed in ex vivo isolated human T cells. This approach should contribute to improving current protocols of anticancer immunetherapy protocols.

Inflammation and Atrial Electrical Remodelling in Patients With Embolic Strokes of Undetermined Source.

BACKGROUND: About one third of ischaemic strokes are classified as embolic strokes of undetermined source (ESUS). A silent atrial fibrillation (AF) may play a pathogenic role in these strokes and P wave dispersion (PWD), representing an electrocardiographic (ECG) predictor for paroxysmal AF, thereby a potential marker of covert cardioembolism, was found to be increased in cryptogenic stroke. Furthermore, current evidence links AF to inflammation: inflammatory markers, such as high-sensitive C-reactive protein (hsCRP), have been related to the development and persistence of AF, possibly by promoting atrial remodelling. The aim of this study was to evaluate whether a relationship between PWD and hsCRP in patients with ESUS exists, in order to highlight a possible role for inflammation in the atrial electric remodelling, that predisposes to AF. METHODS: We enrolled 174 patients (91 males, 83 females; mean age 69±13years) with ESUS. All patients underwent neuroimaging examination, arterial ultrasound examination, echocardiography and ECG. P wave dispersion and hsCRP were measured in all subjects. RESULTS: A significant positive correlation was found between hsCRP and PWD (Spearman r: 0.35, p<0.0001). In patients with high PWD (>40 msec; n=102), hsCRP was three-fold higher than in patients with normal PWD (≤40 msec; n=72)(1.57±2.9 vs 0.42±0.4mg/dl, p=0.0005). CONCLUSIONS: Our results show increased hsCRP levels in cryptogenic stroke patients with high PWD. These findings provide support for the hypothesis that systemic inflammation plays a role in a fraction of patients with ESUS, by increasing AF risk via atrial electric remodelling.