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Background and Aims: Atrial fibrillation (AF) is the most important cause of embolic stroke of undetermined source (ESUS). Implantable loop recorder (ILR) demonstrated the highest sensitivity for detecting it. This register was created to confirm the high prevalence of AF in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA (Transient Ischaemic Attack)/stroke recurrence and death using ILR. Methods: A total of 278 patients admitted to “Molinette” Hospital in Stroke Unit department between 2011 and 2016, diagnosed with ESUS, underwent ILR implantation if they had at least one risk factor for AF. A total of 165 patients admitted to other departments in the same center for the same pathology, without ILR, represent the control group. We used propensity score to select 132 patients from each group (matching age, sex, CHADS-VASC, and HAS-BLEED baseline characteristics). Results: The detection rate of AF episodes was significantly higher in the ILR group (p < 0.001). No significant protective role of ILR for clinical endpoints was found on univariate analysis, although a trend towards significance has been pointed for the composite outcome of death and ischemic events recurrence (OR 0.52, CI 0.26–1.04, p = 0.06). A protective role of ILR was found for deaths (OR 0.4, CI 0.17–0.94, p 0.03) and for the composite outcome (OR 0.41, CI 0.19–0.87, p 0.02) on multivariate analysis in the best subsets. Conclusion: With our statistical models, we identified a significant clinical benefit from ILR monitoring, evidenced by a trend of less death and TIA/stroke recurrence and relevant ILR protection for prediction of TIA/stroke recurrence.

Background and Aims AF (Atrial Fibrillation) is the most important cause of Embolic Stroke of Undetermined Source (ESUS). Implantable Loop Recorder (ILR) demonstrated the highest sensitivity for detecting post-stroke asymptomatic AF. This register was created to assess the prevalence of AF episodes in patients after ESUS and to verify possible benefits on clinical outcomes such as TIA or stroke recurrence and death using ILR. Methods 278 patients admitted to the Stroke Unit of “Città della Salute e della Scienza” hospital in Torino between 2011 and 2019, underwent ILR implantation if they had at least one risk factor for AF including obesity, hyperthyroidism, atrial enlargement at transthoracic echocardiography, severe mitral valve disease, CHADS-VASc score ≥ 4, age > 70 years old and diabetes. The control group was composed of 165 patients admitted in other departments of the same hospital diagnosed with ESUS, not implanted with ILR. We used propensity score matching to select 132 patients from each group (matching age, sex, CHADS-VASc, and HAS-BLED baseline characteristics). Risk and protective factors were estimated for clinical outcomes (deaths and TIA or stroke recurrence) and were evaluated with logistic regression univariate and multivariate analyses. Results The detection rate of AF episodes longer than 5 minutes was significantly higher in the ILR group (41.7% vs 15.9%, p On univariate analysis, we found a trend towards a protective role of ILR for the composite outcome of TIA or stroke recurrence and mortality (OR 0.52, CI 0.26–1.04, p 0.06). On multivariate analysis, we found a protective role of ILR in terms of deaths (OR 0.4, CI 0.17–0.94, p 0.03) and for the composite outcome of ischemic event recurrences and deaths (OR 0.41, CI 0.19–0.87, p 0.02). Age was consistently identified as a risk factor for all the clinical outcomes. Conclusion In patients with ESUS and at least one risk factor for AF, episodes of AF longer than 5 minutes are identified in 41.7% of the cases thanks to ILR. Our study demonstrated that a policy including ILR in patients with ESUS also gives a clinical benefit in terms of TIA or stroke recurrence and death, although limited size of the population and possible presence of selection bias may limit the generalisation of our results.

BackgroundClinical trials and observational studies have demonstrated the benefit of thrombectomy up to 16 or 24 hours after the patient was last known to be well. This study aimed to evaluate the outcome of stroke patients treated beyond 24 hours from onset.MethodsWe analyzed the outcome of 34 stroke patients (mean age 70.7±12.3 years; median National Institutes of Health Stroke Scale (NIHSS) score 13) treated with endovascular thrombectomy beyond 24 hours from onset who were recruited in the Italian Registry of Endovascular Thrombectomy in Acute Stroke. Selection criteria for patients were: pre-stroke modified Rankin scale (mRS) score of ≤2, non-contrast CT Alberta Stroke Program Early CT score of ≥6, good collaterals on single phase CT angiography (CTA) or multiphase CTA, and CT perfusion mismatch with an infarct core size ≤50% of the total hypoperfusion extent or involving less than one-third of the extent of the middle cerebral artery territory evaluated by visual inspection. The primary outcome measure was functional independence assessed by the mRS at 90 days after onset. Safety outcomes were 90 day mortality and the occurrence of symptomatic intracranial hemorrhage (sICH).ResultsSuccessful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was present in 76.5% of patients. Three month functional independence (mRS score 0–2) was observed in 41.1% of patients. The case fatality rate was 26.5%. and the incidence of sICH was 8.8%.ConclusionsThese findings suggest that, in a real world setting, very late endovascular therapy is feasible in appropriately selected patients.

We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24 h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24 h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion.

Long-term consequences of cervical artery dissection (CeAD), a major cause of ischemic stroke in young people, have been poorly investigated. The Italian Project on Stroke at Young Age - Cervical Artery Dissection (IPSYS CeAD) project is a multicenter, hospital-based, consecutively recruiting, observational, cohort study aimed to address clinically important questions about long-term outcome of CeAD patients, which are not covered by other large-scale registries. Patients with radiologically diagnosed CeAD were consecutively included in the registry. Baseline demographic and clinical variables, as well as information on risk factors, were systematically collected for each eligible patient. Follow-up evaluations were conducted between 3 and 6 months after the initial event (t1) and then annually (t2 at 1 year, t3 at 2 years , and so on), in order to assess outcome events (long-term recurrent CeAD, any fatal/nonfatal ischemic stroke, transient ischemic attack (TIA), or other arterial thrombotic event, and death from any cause). Between 2000 and 2019, data from 1530 patients (age at diagnosis, 47.2 ± 11.5 years; women, 660 [43.1%]) have been collected at 39 Italian neurological centers. Dissection involved a single vessel in 1308 (85.5%) cases and caused brain ischemia in 1303 (85.1%) (190 TIA/1113 ischemic stroke). Longitudinal data are available for 1414 (92.4%) patients (median follow-up time in patients who did not experience recurrent events, 36.0 months [25th to 75th percentile, 63.0]). The collaborative IPSYS CeAD effort will provide novel information on the long-term outcome of CeAD patients. This could allow for tailored treatment approaches based on patients' individual characteristics.

Background and purpose We sought to investigate whether there are gender differences in clinical outcome after stroke due to large vessel occlusion (LVO) after mechanical thrombectomy (EVT) in a large population of real-world patients. Methods From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke due to large vessel occlusion. We compared clinical and safety outcomes in men and women who underwent EVT alone or in combination with intravenous thrombolysis (IVT) in the total population and in a Propensity Score matched set. Results Among 3422 patients included in the study, 1801 (52.6%) were women. Despite older age at onset (mean 72.4 vs 68.7; p Conclusions Subject to the limitations of a non-randomized comparison, women with stroke due to LVO treated with mechanical thrombectomy had a better chance to achieve complete recanalization, and 3-month functional independence than men. The results could be driven by women who underwent combined treatment.

ObjectiveTo explore the impact of antithrombotic therapy discontinuation in the postacute phase of cervical artery dissection (CeAD) on the mid-term outcome of these patients.MethodsIn a cohort of consecutive patients with first-ever CeAD, enrolled in the setting of the multicentre Italian Project on Stroke in Young Adults Cervical Artery Dissection, we compared postacute (beyond 6 months since the index CeAD) outcomes between patients who discontinued antithrombotic therapy and patients who continued taking antithrombotic agents during follow-up. Primary outcome was a composite of ischaemic stroke and transient ischaemic attack. Secondary outcomes were (1) Brain ischaemia ipsilateral to the dissected vessel and (2) Recurrent CeAD. Associations with the outcome of interest were assessed by the propensity score (PS) method.ResultsOf the 1390 patients whose data were available for the outcome analysis (median follow-up time in patients who did not experience outcome events, 36.0 months (25th–75th percentile, 62.0)), 201 (14.4%) discontinued antithrombotic treatment. Primary outcome occurred in 48 patients in the postacute phase of CeAD. In PS-matched samples (201 vs 201), the incidence of primary outcomes among patients taking antithrombotics was comparable with that among patients who discontinued antithrombotics during follow-up (5.0% vs 4.5%; p(log rank test)=0.526), and so was the incidence of the secondary outcomes ipsilateral brain ischaemia (4.5% vs 2.5%; p(log rank test)=0.132) and recurrent CeAD (1.0% vs 1.5%; p(log rank test)=0.798).ConclusionsDiscontinuation of antithrombotic therapy in the postacute phase of CeAD does not appear to increase the risk of brain ischaemia during follow-up.

Introduction To describe clinical, neuroimaging, and laboratory features of a large cohort of Italian patients with reversible cerebral vasoconstriction syndrome. Methods In the setting of the multicenter Italian Project on Stroke at Young Age (IPSYS), we retrospectively enrolled patients with a diagnosis of definite reversible cerebral vasoconstriction syndrome according to the International Classification of Headache Disorders (ICHD)-3 beta criteria (6.7.3 Headache attributed to reversible cerebral vasoconstriction syndrome, imaging-proven). Clinical manifestations, neuroimaging, treatment, and clinical outcomes were evaluated in all patients. Characteristics of reversible cerebral vasoconstriction syndrome without typical causes (“idiopathic reversible cerebral vasoconstriction syndrome”) were compared with those of reversible cerebral vasoconstriction syndrome related to putative causative factors (“secondary reversible cerebral vasoconstriction syndrome”). Results A total of 102 patients (mean age, 47.2 ± 13.9 years; females, 85 [83.3%]) qualified for the analysis. Thunderclap headache at presentation was reported in 69 (67.6%) patients, and it typically recurred in 42 (60.9%). Compared to reversible cerebral vasoconstriction syndrome cases related to putative etiologic conditions (n = 21 [20.6%]), patients with idiopathic reversible cerebral vasoconstriction syndrome (n = 81 [79.4%]) were significantly older (49.2 ± 13.9 vs. 39.5 ± 11.4 years), had more frequently typical thunderclap headache (77.8% vs. 28.6%) and less frequently neurological complications (epileptic seizures, 11.1% vs. 38.1%; cerebral infarction, 6.1% vs. 33.3%), as well as concomitant reversible brain edema (25.9% vs. 47.6%). Conclusions Clinical manifestations and putative etiologies of reversible cerebral vasoconstriction syndrome in our series are slightly different from those observed in previous cohorts. This variability might be partly related to the coexistence of precipitating conditions with a putative etiologic role on disease occurrence.

Aim An underlying atrial vulnerability or a preexisting misdiagnosed atrial fibrillation in some patients who are candidates for patent foramen ovale (PFO) closure may lead to an unnecessary percutaneous intervention. The aim of this work was to define paroxysmal atrial fibrillation rate, through a 6-month insertable loop-recorder monitoring, in patients over 55 years old with cryptogenic stroke and PFO. Methods PFO closure criteria: significant right-to-left shunt and at least one high-risk feature (permanent right-to-left shunt, atrial septal aneurysm, prominent Eustachian valve, recurrent brain ischemia, previous deep vein thrombosis, thrombophilia). Insertable cardiac monitoring criteria: previous cryptogenic stroke, more than 55 years and at least one atrial fibrillation risk factor (heart failure, hypertension, age older than 65 years, diabetes, atrial runs, left atrium dilatation, left ventricle hypertrophy, pulmonary disease, thyroid disease, obesity). Atrial fibrillation detection threshold: arrhythmia duration longer than 5 min. Results From January 2008 to March 2017, 195 patients underwent to loop-recorder monitoring. A total of 70 (36%) patients were candidates for PFO closure. The 6-month silent atrial fibrillation rate was 11.4%. In the arrhythmia-free cohort, 28 patients (45.2%) underwent percutaneous foramen ovale closure (group A) and 34 (54.8%) were medically treated (group B). Atrial fibrillation detection rate was 14.3% in group A and 0% in group B. The 36-month atrial fibrillation-free survival was 76%. Conclusion An occult preexisting atrial fibrillation may lead to unnecessary percutaneous foramen ovale closure in a significant proportion of patients. A 6-month loop-recorder monitoring may improve the patient oriented decision-making.

BACKGROUND AND PURPOSE Evaluation of the diagnostic accuracy of optic nerve sheath diameter (ONSD) and Doppler indices of central retinal arteries and veins for the detection of increased intracranial pressure (ICP) in intracerebral hemorrhage (ICH) and of the usefulness of a second assessment of these variables in the monitoring of ICH. METHODS A total of 46 acute ICH patients with (group 1, n = 25) and without (group 2, n = 21) clinical and radiological computed tomography signs of raised ICP and 40 healthy controls were recruited. The median binocular ONSD and Doppler indices of retinal vessels including resistive index (RI) and retinal venous pulsation (RVP) were compared among groups, both at admission and later during ICH monitoring. RESULTS Median binocular ONSD showed higher accuracy for the detection of increased ICP (sensitivity and specificity 100%), while Doppler indices were less accurate (sensitivity 48% and specificity 95% for RI; 80% and 62% for RVP). In ICH patients, ONSD was significantly elevated in group 1 both at admission (6.40 mm [interquartile range [IQR] = .70] vs. 4.70 [.40]) and at control time (6.00 [.55] vs. 4.55 [.40]; P

Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia and spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions have distinctive clinical characteristics has not been extensively investigated. Methods: In a cohort of consecutive patients with first-ever sCeAD, enrolled in the setting of the multicenter IPSYS CeAD study (Italian Project on Stroke in Young Adults Cervical Artery Dissection) between January 2000 and June 2019, we compared demographic and clinical characteristics, risk factor profile, vascular pathology, and midterm outcome of patients with coexistent cerebrovascular fibromuscular dysplasia (cFMD; cFMD+) with those of patients without cFMD (cFMD–). Results: A total of 1283 sCeAD patients (mean age, 47.8±11.4 years; women, 545 [42.5%]) qualified for the analysis, of whom 103 (8.0%) were diagnosed with cFMD+. In multivariable analysis, history of migraine (odds ratio, 1.78 [95% CI, 1.13–2.79]), the presence of intracranial aneurysms (odds ratio, 8.71 [95% CI, 4.06–18.68]), and the occurrence of minor traumas before the event (odds ratio, 0.48 [95% CI, 0.26–0.89]) were associated with cFMD. After a median follow-up of 34.0 months (25th to 75th percentile, 60.0), 39 (3.3%) patients had recurrent sCeAD events. cFMD+ and history of migraine predicted independently the risk of recurrent sCeAD (hazard ratio, 3.40 [95% CI, 1.58–7.31] and 2.07 [95% CI, 1.06–4.03], respectively) in multivariable Cox proportional hazards analysis. Conclusions: Risk factor profile of sCeAD patients with cFMD differs from that of patients without cFMD. cFMD and migraine are independent predictors of midterm risk of sCeAD recurrence.

BACKGROUND AND PURPOSE The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Supplemental Digital Content is available in the text., Background and Purpose: We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak. Methods: The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units. We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period). Results: Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71–0.80] P

Background and Purpose: As numerous questions remain about the best anesthetic strategy during thrombectomy, we assessed functional and radiological outcomes in stroke patients treated with thrombectomy in presence of general anesthesia (GA) versus conscious sedation (CS) and local anesthesia (LA). Methods: We conducted a cohort study on prospectively collected data from 4429 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Results: GA was used in 2013 patients, CS in 1285 patients, and LA in 1131 patients. The rates of 3-month modified Rankin Scale score of 0–1 were 32.7%, 33.7%, and 38.1% in the GA, CS, and LA groups: GA versus CS: odds ratios after adjustment for unbalanced variables (adjusted odds ratio [aOR]), 0.811 (95% CI, 0.602–1.091); and GA versus LA: aOR, 0.714 (95% CI, 0.515–0.990). The rates of modified Rankin Scale score of 0–2 were 42.5%, 46.6%, and 52.4% in the GA, CS, and LA groups: GA versus CS: aOR, 0.902 (95% CI, 0.689–1.180); and GA versus LA: aOR, 0.769 (95% CI, 0.566–0.998). The rates of 3-month death were 21.5%, 19.7%, and 14.8% in the GA, CS, and LA groups: GA versus CS: aOR, 0.872 (95% CI, 0.644–1.181); and GA versus LA: aOR, 1.235 (95% CI, 0.844–1.807). The rates of parenchymal hematoma were 9%, 12.6%, and 11.3% in the GA, CS, and LA groups: GA versus CS: aOR, 0.380 (95% CI, 0.262–0.551); and GA versus LA: aOR, 0.532 (95% CI, 0.337–0.838). After model of adjustment for predefined variables (age, sex, thrombolysis, National Institutes of Health Stroke Scale, onset-to-groin time, anterior large vessel occlusion, procedure time, prestroke modified Rankin Scale score of Conclusions: GA during thrombectomy was associated with worse 3-month functional outcomes, especially when compared with LA. The inclusion of an LA arm in future randomized clinical trials of anesthesia strategy is recommended.

Background There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. Aims We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. Methods From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. Results The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p Conclusions Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits.

Background The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance. Aims We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy Methods We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3–6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC). Results A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training ( n = 1219) and test ( n = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816–0.869) in the training set, and 0.820 (95% CI: 0.786–0.854) in the test set. Conclusions The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome.

Comprehending the nature of tactile disorders following brain damage is crucial to understand how the brain constructs sensory awareness. Stroke patients may be unaware of being touched on the affected hand if, simultaneously, they are touched on the unaffected hand (i.e., tactile extinction). More rarely, they feel touches on the two hands, when they are solely touched on the unaffected hand (i.e., synchiria). Using a novel assessment tool, we investigated whether in stroke patients with apparent intact tactile awareness on standard evaluation, tactile extinction might be possibly masked by phantom (synchiric) sensations (i.e., elicited by ipsilesional stimulation) arising exclusively during Double Simultaneous Stimulation (DSS). Patients with right (n = 17) and left (n = 8) hemisphere lesions and age-matched healthy controls (n = 13) were tested with the Tactile Quadrant Stimulation test, consisting in delivering unilateral or bilateral touches to one of four quadrants, identified on the participants' hands. In DSS trials, stimuli were applied to asymmetric quadrants. Participants reported the side(s) and then pointed to the site(s) of stimulation. We found that, with the exception of one patient who showed tactile extinction, about 50% of patients with overall intact tactile perception on classical evaluation, although reporting two stimuli in DSS, failed in pointing to the correct contralesional stimulated site. They reported the felt sensation in positions that corresponded to the ipsilesional stimulated sites. Thus apparent detections of contralesional touches in DSS were accounted for by ‘phantom’ sensations of ipsilesional stimulation that masked unawareness of contralesional touches when classic assessment was applied. Preliminary lesion analyses indicate that the symptom was associated with damage to structures often affected in tactile extinction. These findings, while unveiling important underestimation of the patients' neurological condition, provide a framework for investigating bihemispheric contributions to altered tactile perception following stroke.

The acute distal intracranial occlusion of the internal carotid artery (ICA) is a very complex heterogeneous pathology, characterized by various patterns. Aim of this work is to identify the different types and propose a classification. Among the patients admitted for stroke in the anterior circulation from august 2014 to October 2017, 46 (25%) presented with intracranial distal carotid artery occlusion. The mean age of the patients was 71 (SD 13.7), 65,2% female. The protocol included general and specific neurological examinations, CT, CT-Angiography with multiphase CTA, followed by Angiography. The occlusion was treated by aspiration device alone or associated with stent-retriever. NIHSS at the admission, at discharge and modified ranking Scale (mRS) at four months were examined. The occlusions presented with various patterns. Depending on its site (located at the distal ICA bifurcation or more proximal at the level of the ophthalmic segment of ICA, with or without extent to ICA bifurcation) taking also into account the various involvement of the cerebral vessels and anatomic variations of Circle of Willis, three groups of occlusion types could be identified (T1, T2 and T3). The collateral circulation, and the possibilities of the endovascular revascularization important for the final outcome, were clearly connected with the type of occlusion. NIHSS at admission was 19.1 (Range from 8 to 30, SD 4.4). Good outcome defined as mRS 0-2 at for months was obtained in 17 patients (37%). The proposed classification reproduces more precisely the complexity and heterogeneity of this pathology, being useful in the diagnosis and treatment of these patients.

Mutations in COL4A1, encoding one of the six collagen type IV proteins, cover a wide spectrum of autosomal dominant overlapping phenotypes including porencephaly, small-vessel disease and hemorrhagic stroke, leukoencephalopathy, hereditary angiopathy with nephropathy, aneurysms and muscle cramp (HANAC) syndrome, and Walker-Warburg syndrome. Over 50 mutations are known, mainly being missense changes. Intra- and inter-familial variability has been reported. We studied two Italian families in which the proband had a clinical diagnosis of COL4A1-related disorder. We found two novel mutations (c.1249G>C; p.Gly417Arg and c.2662G>C; p.Gly888Arg). Both involved highly conserved amino acids and were predicted as being deleterious by bioinformatics tools. The c.1249G>C (p.Gly417Arg) segregated in four subjects with variable neurological phenotypes, namely leukoencephalopathy with muscle symptoms, brain small-vessel disease, and mild infantile encephalopathy. A fourth case was a carrier of the mutation without any neurological symptoms and an MRI with a specific white matter anomaly. The c.2662G>C (p.Gly888Arg) mutation was de novo in the proband. After a temporary motor impairment at age 14, the subject complained of mild imbalance at age 30, during the third trimester of her twin pregnancy, when an anomaly of the left brain hemisphere was documented in one fetus. Both her male dizygotic twins presented a severe motor delay, early convulsions, and leukoencephalopathy, and were carriers of the mutation. In summary, we confirm that high intra-familial variability of COL4A1 mutations with very mild phenotypes, the apparent incomplete penetrance, and de novo changes may become a "dilemma" for clinicians and genetic counselors.

Although sparse observational studies have suggested a link between migraine and cervical artery dissection (CEAD), any association between the 2 disorders is still unconfirmed. This lack of a definitive conclusion might have implications in understanding the pathogenesis of both conditions and the complex relationship between migraine and ischemic stroke (IS).To investigate whether a history of migraine and its subtypes is associated with the occurrence of CEAD.A prospective cohort study of consecutive patients aged 18 to 45 years with first-ever acute ischemic stroke enrolled in the multicenter Italian Project on Stroke in Young Adults was conducted between January 1, 2000, and June 30, 2015. In a case-control design, the study assessed whether the frequency of migraine and its subtypes (presence or absence of an aura) differs between patients whose IS was due to CEAD (CEAD IS) and those whose IS was due to a cause other than CEAD (non-CEAD IS) and compared the characteristics of patients with CEAD IS with and without migraine.Frequency of migraine and its subtypes in patients with CEAD IS vs non-CEAD IS.Of the 2485 patients (mean [SD] age, 36.8 [7.1] years; women, 1163 [46.8%]) included in the registry, 334 (13.4%) had CEAD IS and 2151 (86.6%) had non-CEAD IS. Migraine was more common in the CEAD IS group (103 [30.8%] vs 525 [24.4%], P = .01), and the difference was mainly due to migraine without aura (80 [24.0%] vs 335 [15.6%], P .001). Compared with migraine with aura, migraine without aura was independently associated with CEAD IS (OR, 1.74; 95% CI, 1.30-2.33). The strength of this association was higher in men (OR, 1.99; 95% CI, 1.31-3.04) and in patients 39.0 years or younger (OR, 1.82; 95% CI, 1.22-2.71). The risk factor profile was similar in migrainous and non-migrainous patients with CEAD IS (eg, hypertension, 20 [19.4%] vs 57 [24.7%], P = .29; diabetes, 1 [1.0%] vs 3 [1.3%], P .99).In patients with IS aged 18 to 45 years, migraine, especially migraine without aura, is consistently associated with CEAD. This finding suggests common features and warrants further analyses to elucidate the underlying biologic mechanisms.

BACKGROUND: Crossing the hands over the midline can reduce the perceived intensity of nociceptive stimuli applied onto the hands. It remains unclear to what extent intact representation of peripersonal space influences this effect. Here we used the crossed-hands paradigm in patients with unilateral spatial neglect, a neuropsychological condition characterized by the inability to detect, attend and respond to contralesional (most often left) stimuli, and spared ability to process stimuli in the non-affected space. METHODS: Sixteen post-stroke patients without unilateral neglect and 11 patients with unilateral spatial neglect received punctate mechanical pinprick stimuli onto their crossed or uncrossed hands. We tested: (i) whether deficits in space representation reduce the possibility of observing 'crossed-hands analgesia', and; (ii) whether placing the contralesional hand, normally lying in the affected space in the healthy space would increase the number of detected stimuli. RESULTS: Our results showed that neglect patients did not exhibit 'crossed-hands' analgesia, but did not provide strong evidence for an improvement in the number of detected stimuli when the contralesional hand was in the healthy space. CONCLUSION: These findings uphold the notion that the perception of nociceptive stimuli is modulated by the relative position of the hands in space, but raise questions about the conditions under which these effects may arise. SIGNIFICANCE: We show that deficits in space representation can influence the processing of mechanical pinprick stimuli. Our results raise several questions on the mechanisms underlying these effects, which are relevant for the clinical practice.

AIM There is still controversy regarding the benefit of percutaneous closure of patent foramen ovale (PFO) among patients with cryptogenic stroke. Here we aimed to evaluate the factors associated with treatment choice and predictors of adverse events in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO. METHODS Of 418 consecutive patients with PFO and cryptogenic stroke or TIA, 262 underwent percutaneous PFO closure, whereas 156 were medically treated. Multivariable logistic regression models were developed to evaluate factors influencing the treatment strategy and predictors of outcome, a composite of stroke, TIA or all-cause mortality. RESULTS Patients with large interatrial right-to-left shunt were more likely treated with percutaneous closure [odds ratio (OR) = 4.79, 95% confidence interval (2.73-8.42); P

Atrial fibrillation is responsible for up to one-third of ischemic strokes, and is also associated with silent cerebral infarctions and transient ischemic attacks (TIAs). The self-terminating and often asymptomatic nature of paroxysmal atrial fibrillation (PAF) may lead to its underdiagnosis. A continuous and long-term heart rhythm monitoring can be useful in unmasking PAF episodes.Prevalence of asymptomatic PAF in patients suffering a cryptogenic stroke, at risk for atrial fibrillation but without any history of arrhythmia or palpitations, using a continuous electrocardiographic monitoring.One hundred and forty-two consecutive patients were admitted to the Stroke Unit of 'Città della Salute e della Scienza' Hospital of Turin between June 2010 and March 2013 and discharged with the diagnosis of ischemic cryptogenic stroke. Sixty fulfilled predefined inclusion criteria. Follow-up was carried on and completed for the 54 patients who consented to implantable loop recorder (ILR) implantation. After ILR implantation, trans-telephonic data were collected monthly.Atrial fibrillation episodes lasting more than 5 min were recorded in 25 patients (46%), median detection time was 5.4 months (range 1-18) and median duration of atrial fibrillation episodes was 20 h (range 7 min-8 days) with 19 patients (76%) remaining asymptomatic and the others experiencing weakness and dyspnoea but not palpitations.Long-term heart rhythm monitoring is successful in unmasking silent atrial fibrillation in 46% of patients suffering a cryptogenic stroke with concomitant atrial fibrillation risk factors, but without history of arrhythmia or palpitations.

Background— We sought to compare the benefit of percutaneous closure to that of medical therapy alone for the secondary prevention of embolism in patients with patent foramen ovale (PFO) and otherwise unexplained ischemic stroke, in a propensity scored study. Methods and Results— Between 2000 and 2012, we selected consecutive first-ever ischemic stroke patients aged 18 to 45 years with PFO and no other cause of brain ischemia, as part of the IPSYS registry (Italian Project on Stroke in Young Adults), who underwent either percutaneous PFO closure or medical therapy for comparative analysis. Primary end point was a composite of ischemic stroke, transient ischemic attack, or peripheral embolism. Secondary end point was brain ischemia. Five hundred and twenty-one patients qualified for the analysis. The primary end point occurred in 15 patients treated with percutaneous PFO closure (7.3%) versus 33 patients medically treated (10.5%; hazard ratio, 0.72; 95% confidence interval, 0.39–1.32; P =0.285). The rates of the secondary end point brain ischemia were also similar in the 2 treatment groups (6.3% in the PFO closure group versus 10.2% in the medically treated group; hazard ratio, 0.64; 95% confidence interval, 0.33–1.21; P =0.168). Closure provided a benefit in patients aged 18 to 36 years (hazard ratio, 0.19; 95% confidence interval, 0.04–0.81; P =0.026) and in those with a substantial right-to-left shunt size (hazard ratio, 0.19; 95% confidence interval, 0.05–0.68; P =0.011). Conclusions— PFO closure seems as effective as medical therapy for secondary prevention of cryptogenic ischemic stroke. Whether device treatment might be more effective in selected cases, such as in patients younger than 37 years and in those with a substantial right-to-left shunt size, deserves further investigation.

i.v. Thrombolysis (IVT) is the most important achievement of the last 20 years in the field of ischemic stroke management. In Italy, the evidence that stroke units were effective per se in improving stroke outcome was not sufficient to favor their implementation. Only the approval of IVT boosted the activation of stroke units, which are now 170 centers widespread over the country. The numbers of treatments, however, are still limited, amounting in 2014 to approximately 4200 out of the 10 000 which should theoretically be performed each year. Too strict exclusion criteria and/or their too restrictive interpretation are two of the main causes of this substantial undertreatment. Hence, a critical reappraisal of these criteria was necessary. On the other hand, recent evidences on the potentialities of intra-arterial interventions made it mandatory to better define the role of these techniques in the chain of treatments for acute ischemic stroke. A panel of vascular neurologists (D. T., D. I., A. C., E. A., P. C., A. Z.) and of interventional neuro-radiologists (S. M., S. V., M. B.) collected the data through a systematic review of the available literature, searching electronic databases including PubMed, EMBase, OVID, and Cochrane Library, up to May 2015. Reference lists of the selected articles were also scrutinized. Each panelist was assigned individual sections, then the panel assessed the complete guidelines. Recommendations were formulated by integrating the principles of the Scottish Intercollegiate Guideline Network with the statistical considerations suggested by the Centre for EvidenceBased Medicine methodology (Table 1). When literature data and practice experience data were not available or not considered to be sufficient, no specific recommendation was made. Consensus was reached during face-to-face discussions. In case of disagreement, a majority decision was taken. Recommendations were then revised by a larger group of experts pertaining to the fields of trial methodology, vascular neurology, cardiology, emergency medicine, neurosurgery, vascular surgery, neuro-radiology, and rehabilitation (see Appendix S1), which in particular checked for the congruence between the grading and the source data.

Evaluate Magnetic Resonance (MR) and Magnetic Resonance Angiography (MRA) sensibility in the diagnosis and follow-up of dissection of Internal Carotid and Vertebral Artery (ICA/VA). We revalued MR examination of 36 patients, 24 men, 12 women, aged 18-69 years. All patients underwent brain TC and MR (GE 1 Tesla); in 16 subjects 3D Time-of-Flight (TOF-3D) MRA was performed and in 20 subjects a Contrast-Enhanced MRA (CEMRA) of neck and head arteries. Thirty-one patients underwent a MRA follow-up. Dissection involved ICA in 30 and VA in 8. MR showed ischemic signs in 25 cases, wall hematoma in 19, and was normal in 11. MRA showed 25 vessels stenosis, 12 occlusions, and 9 aneurysm. Follow-up MRA showed 6 cases of complete resolution of stenosis, 17 partial resolution, 2 aneurysmal dissecanting, 6 luminal alteration unchanged, 1 aneurysma enlarged. MRA represented a non-invasive technique as investigation in suspected cervicocephalic arteries dissection.

OBJECTIVES: To determine whether patients undergoing carotid endarterectomy (CE) for symptomatic left internal carotid artery (LICA) stenosis have greater risk of cognitive decline than patients with asymptomatic LICA disease or right internal carotid artery (RICA) disease. DESIGN: Observational. SETTING: Vascular surgery day hospital. PARTICIPANTS: The analysis included 103 patients (mean age 72.6±7.0, 73 men), of whom 50 had LICA disease (29 symptomatic). MEASUREMENTS: Cognitive function was evaluated (age- and education-adjusted Mini-Mental State Examination (MMSE), and Clock tests (CLOX1 and 2)) at baseline and at the end of the study period (average follow-up±standard deviation 44.4±14.3 months) in a sample of patients aged 65 and older, free from cognitive impairment, consecutively undergoing CE. RESULTS: At the end of the study period, MMSE, CLOX1, and CLOX2 scores were significantly lower in patients with symptomatic LICA disease (P

Background and Purpose— To report results of mechanical disruption or retrieval of thrombus as first-line treatment in patients with stroke attributable to occlusion of the basilar artery, in particular regarding efficiency and safety. Methods— In 12 consecutive patients with acute stroke attributable to basilar occlusion, mechanical disruption or thrombus retrieval using various loop-shaped tools was tried before eventually starting local intra-arterial thrombolysis with recombinant tissue plasminogen activator (r-tPA). Main inclusion criteria were: National Institutes of Health Stroke Scale score >8 or Glasgow Coma Scale score Results— Mechanical recanalization was successful in 6 patients. A single brain infarction, possibly attributable to distal embolization, occurred. Three patients had good outcomes. In 5 of 6 remaining patients, the artery was recanalized using r-tPA. A single asymptomatic hemorrhage occurred; 3 patients had good outcomes. Procedure time and r-tPA were significantly less in patients with successful mechanical thrombolysis (43.33 minutes and 13.33 mg versus 112.33 minutes and 55.83 mg, respectively). Conclusion— Mechanical recanalization was effective in half of the patients and at least as safe as local intra-arterial thrombolysis. It allowed to save r-tPA and time. Although the low success rate remains a limit, the excellent and quick anatomical recanalization obtained after successful procedures makes this approach promising.

The risk of cognitive decline in patients undergoing carotid endarterectomy (CE) for left internal carotid artery (ICA) (LICA) disease before or after the occurrence of ischemic symptoms has not been fully elucidated. We evaluated whether patients undergoing CE for symptomatic LICA stenosis have greater risk of cognitive decline than patients with asymptomatic LICA disease or right ICA disease.In a series of patients aged 65 years and older, consecutively undergoing CE and free from cognitive impairment, cognitive function was evaluated through the age- and education-adjusted Mini Mental State Examination and the Clock Drawing Task at baseline and at the end of the study period (average follow-up: 44.4 +/- 14.3 months).The analysis included 103 patients (mean age 72.6 +/- 7.0 years; 73 men), of whom 50 had LICA disease (29 symptomatic). At the end of the study period, Mini Mental State Examination score was reduced in patients with symptomatic LICA disease (P.001) but not in other patients, whereas the Clock Drawing Task score was reduced in both patients with LICA and right ICA. Patients with symptomatic LICA disease had greater risk of cognitive decline than other individuals, either measured by the Mini Mental State Examination score (F = 5.18, P = .002) or by the Clock Drawing Task score (F = 9.42, P = .001).Patients undergoing CE for symptomatic LICA disease appear to be at increased risk of cognitive decline than other individuals. Further studies are needed to confirm these findings and to evaluate whether LICA endarterectomy before occurrence of cerebrovascular ischemic symptoms may provide additive benefit in the prevention of cognitive decline.

The objective was to describe the clinical features and management of cerebral venous thrombosis (CVT) in non-selected centres. An observational study in 11 neurological departments in NW Italy was carried out from 1995 through 1999 on 38 female and 10 male patients. Mean age: 44.8 years, SD=14.3. Onset: acute in 21 patients (44%), subacute in 17 (35%) and chronic in 10 (21%). Most frequent onset: with focal deficits and/or seizures, followed by impaired consciousness or confusion, isolated headache, isolated intracranial hypertension and cavernous syndrome. No risk factor was found in 8 patients (17%). The superior sagittal sinus was involved in 27 patients (56%) and the transverse sinus in 29 (60%). Anticoagulants were used in 45 patients (94%). Rankin Scale score at discharge: 0 (27 patients), 1 (four), 2 (five), 3 (five), 4 (none), 5 (one) and six were dead. Thirteen patients had deep CVT: age, risk factors, neurological signs and outcome differed from cortical CVT (35 patients), although not significantly. Clinical features, risk factors and outcome of CVT patients from non-selected centres are similar to those from specialised centres.

Expression of intracellular heat shock protein 27 (Hsp27) rises in the brain of animal models of cerebral ischemia and stroke. Hsp27 is also released into the circulation and the aim of the present study was to investigated if serum Hsp27 (sHsp27) levels are altered in patients with acute ischemic stroke. sHsp27 was measured in 15 patients with acute ischemic stroke and in 14 control subjects comparable for age, sex, and cardiovascular risk factors. In patients, measurements were performed at admission and 1, 2, and 30 days thereafter. At admission, mean sHsp27 values were threefold higher in patients than in controls. In patients, sHsp27 values dropped after 24 h, rose again at 48 h, and markedly declined at 30 days, indicating the presence of a temporal trend of sHsp27 values following acute ischemic stroke.

We describe a 30-year-old woman with an infantile-onset epilepsy due to a left temporal gliotic area who developed a nonconvulsive status epilepticus (NCSE) during tiagabine (TGB) adjunctive therapy. The ictal EEG recording showed a de novo right temporal focus not previously evident. After the i.v. administration of 4mg lorazepam, the NCSE episode rapidly resolved and her usual left temporal EEG abnormalities reappeared. To our knowledge this is the first case of paradoxical seizure exacerbation associated with TGB therapy in which the clinical and EEG features are congruous with a new contralateral focus.

We studied the records of 175 consecutive patients referred to our neurologic ward between January 1994 and February 2000 with a diagnosis of ischaemic cerebrovascular disease (ICVD) (stroke or transient ischaemic attack – TIA) who underwent transoesophageal echocardiography (TEE). We excluded patients with large vessel disease, high-risk embolic cardiopathies and other rare causes of stroke. According to clinical and neuroimaging findings, patients were divided into two groups. The lacunar (LAC) group (69/175 (39.4%)) and the nonlacunar (N-LAC) one (106/175 (60.6%)). The control population consisted of 78 consecutive patients, referred to the echocardiography laboratory for TEE without history of ICVD and known heart disorders. Patent foramen ovale (PFO) frequency was significantly higher in case patients than in control subjects (55/175 (31.4%) vs. 13/78 (16.6%); p = 0.02). Among case patients, PFO was more prevalent in the N-LAC group than in the LAC one (43/106 (40.6%) vs. 12/69 (17.4%); p = 0.0005). A large degree of shunt occurred in 53.5% of N-LAC patients and in 16.7% of LAC ones (p = 0.04). Atrial septal aneurysm (ASA) was detected in 12% of case patients and 1.3% of control subjects (p = 0.003) and was more frequent in the N-LAC group than in the LAC one (16 vs. 5.8%; p = 0.05). Mitral prolapse (MP) was present in 6/175 (3.4%) ICVD patients (vs. 1/78 among controls) in most cases associated with myxomatous valve redundancy. Aortic arch atheromas (AA) were detected in 12% of ICVD patients and in 10.2% of controls. The frequency was 9.4% in N-LAC and 15.9 in LAC. No complicated AA (plaque thickness >4 mm, ulcerated atheroma, superimposed thrombus) were detected. After multivariate analysis, PFO (OR = 3.8; 95% CI = 2.7–7.9) and ASA (OR = 8.01; 95% CI = 3.0–16.1) appeared to be independent predictors of ICVD. PFO (OR = 2.24; 95% CI = 1.24–4.92) was also independently associated with N-LAC stroke subtype and its importance was even higher in younger patients. Our study provides further evidence that TEE is a helpful diagnostic tool in stroke patients without arterial and major cardiac sources of embolism. However, its utility differs according to type and localization of the ischaemic lesion being more relevant in patient with N-LAC infarctions.

Patent foramen ovale (PFO) is a common congenital anatomical defect in the general population with a mean prevalence of 20 %. Transcranial Doppler sonography and echocardiography, both with infusion of agitated saline as an echo contrast, have been introduced for the diagnosis of PFO. Transesophageal echocardiography is considered the gold standard. Several studies have suggested an association between cryptogenetic stroke and PFO, but the role of this condition as a risk factor for stroke is still debated. The aims of this prospective multicentre study are the evaluation of PFO prevalence in the whole ischemic stroke population and the identification of a stroke recurrence profile risk in patients with PFO. All consecutive patients admitted for acute ischemic stroke and with a confirmed diagnosis at discharge are eligible cases for the study. Demographic and vascular risk factors are registered. Clinical severity is summarized by the National Institute of Health stroke scale. Echocardiographic and transcranial studies are performed in each patient to detect the presence of PFO. Prevalence of PFO will be calculated with 95 % CIs. Univariate analysis will be performed to detect the correlation of PFO with different registered factors and multivariable analysis with PFO as independent variable. The present study should contribute to better identify the role of PFO in ischemic stroke risk and recurrence-related events. Qualifying findings of the study are represented by the high number of enrolled patients, the prospective methodology of the study and the presence of secondary instrumental endpoints.

Lipoprotein(a) [Lp(a)] is a plasma lipoprotein that consists of a low-density lipoprotein (LDL)-like particle containing APO B-100 and apolipoprotein(a), linked by a disulphide bridge. There is evidence that higher serum level of Lp(a) is a predictor of various vascular diseases, such as myocardial infarction, coronary stenosis, re-occlusion of aortocoronary bypass vein grafts, peripheral atherosclerosis and cerebral infarction [1-4]. We describe a young man with a cryptogenic stroke with very high serum level of Lp(a) as the only vascular risk factor.

This study tested the association between cognitive functions, cerebrovascular damage, and cerebrovascular reactivity in 71 essential young hypertensives (age matched) and 22 normotensives (age matched). They underwent ambulatory blood pressure monitoring, neurocognitive tests, cerebral magnetic resonance, and transcranial Doppler. Twenty-three percent of patients showed more than 10 white matter lesions and 8% showed none. No control subjects showed more than 10 white matter lesions and 90% of normal controls showed no lesions. Patients with more than 10 white matter alterations had longer hypertensive story and showed significant lower nocturnal blood pressure fall. Pulsatility index was correlated with the number of white matter lesions.

Objective To explore the interaction effects between cardiac interatrial right-to-left shunt (RLS) and proatherosclerotic factors on the risk of brain ischaemia. Design Multicentre Italian case–control study. Setting University hospitals. Participants 588 patients with cryptogenic stroke (CS) aged ≤45 years and 585 control subjects consecutively enrolled as part of the Italian Project on Stroke in Young Adults. Methods Interaction effects between RLS and an individual proatherosclerotic score computed from the number of conventional vascular risk factors for the risk of CS were investigated. Data were examined by logistic regression models and expressed as interaction OR or interaction risk difference (RD). Results CS risk increased with increasing number of proatherosclerotic factors in subjects without RLS (OR 2.73; 95% CI 1.98 to 3.76; RD +0.246; 95% CI +0.17 to +0.32; for subjects with one or more factors), but was higher in subjects with RLS and no additional proatherosclerotic factors (OR 5.14; 95% CI 3.49 to 7.58; RD +0.388; 95% CI +0.31 to +0.47) compared with subjects without RLS and no risk factors. Negative interaction and antagonistic effects between RLS and proatherosclerotic factors were observed (interaction OR 0.52; 95% CI 0.31 to 0.91; interaction RD −0.17; 95% CI −0.29 to −0.05). Conclusions The influence of RLS on the risk of CS decreases with increasing number of atherosclerotic factors, and is highest when such factors are absent. Individual proatherosclerotic profiles may help to identify patients with CS whose patent foramen ovale is probably pathogenic.

To investigate the role of plasma lipid abnormalities in ischemic cerebrovascular disease related to primary vessel disease, the authors assess lipid profiles in a hospital-based cohort of 202 consecutive patients with atherothrombotic or lacunar stroke subtypes. Lipoprotein (a) was the unique lipid parameter that differs between these two subtypes being its value twofold higher in patients with atherothrombotic than in lacunar stroke. This suggests that lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis.

Lacunar ischemic lesions are related to a pathology involving perforators, due to direct changes in the arteries or to an indirect mechanism, such as cardiac or artery to artery embolism, or to hypoperfusion in cases of cardiac failure, or proximal occlusion of large arteries. Changes involving the large intracranial arteries have progressively been taken into consideration as a cause of the disease. This latter aspect is interesting since possible endovascular treatment can be proposed in selected cases. In patients with lacunar syndrome an extended clinical and neuroradiological approach is indicated to choose the most appropriate therapy. Not all lesions recognizable on CT/MR are the expressions of ischemic lesions, this is another important aspect that should be considered in the differential diagnosis.

Cervical artery dissection is an important cause of stroke in young patients and accounts of 10%–20% of stroke or TIA in patients aged less than 50 years. Basilar artery occlusion (BAO) is an infrequent cause of acute stroke, which invariably leads to death or long-term disability if not recanalized. We describe three patients with BAO caused by vertebral dissection, successfully treated with intra-arterial thrombolysis. The lysis of the occluding embolus was obtained by injection of the thrombolytic drug directly or near the thrombus without haemor-rhagic complications. Our cases confirm the safety and efficacy of intra-arterial thrombolysis in patients with BAO due to a vertebral artery dissection.

Acute basilar artery occlusion carries a high risk of disabling stroke or death. Fast recanalization of the vessel is the mainstay of the therapy. Recanalization may be achieved by intravenous or intra-arterial administration of thrombolytics. These procedures are currently used as life-saving interventions, despite the low level of evidence supporting their efficacy, because of the bad prognosis of the disease. Intravenous thrombolysis may be started earlier, but it is less often used, mainly for historic reasons; intra-arterial measures are possibly more effective in achieving recanalization but require extra time before they can be started and demand a considerable amount of resources. The basilar artery does not recanalize in approximately one third of patients; this result has not been modified over the past two decades by these treatments and probably will not change. Combined mechanical and intra-arterial thrombolysis may be more efficient in achieving basilar artery recanalization, but the impact of this combined intervention on the final outcome has not been evaluated. Because time is critical, as in every stroke, implementation of a specific treatment protocol for this condition, including one of the aforementioned treatments, and eventual transfer to a secondary-care unit will save time and improve prognosis.

Moya-Moya is a rare cerebrovascular occlusive disease characterized by bilateral stenosis or occlusion at the terminal portion of the internal carotid artery and abnormal vascular network at the base of the brain, named "moya-moya". In children, Moya-Moya disease usually presents with ischemic cerebrovascular events, mainly TIA or lacunar stroke, leading to mental deterioration. In adults, especially in females, it presents with intracranial haemorrhages. We describe the case of an adult patient with an atherosclerotic Moya-Moya disease which presented with a cerebral borderzone infarction.

P. Cerrato AOU ‘‘Molinette’’, Turin, Italy C. Serrati AO ‘‘S. Martino’’, Genoa, Italy M. Del Sette Neurology Unit, S. Andrea Hospital, Via Vittorio Veneto 197, 19124 La Spezia, Italy A. Cavallini UC Malattie Cerebrovascolari/Stroke Unit, IRCCS ‘‘C. Mondino’’, Pavia, Italy M. Diomedi UOC Stroke Unit, Dipartimento di Neuroscienze, Universita degli Studi di Roma Tor Vergata, Rome, Italy S. Ricci UO Neurologia, ASL 1 dell’Umbria Ospedale, Via Engels, 06012 Citta di Castello (PG), Italy

The aim of this study was to evaluate the risk of recurrent ischaemic cerebrovascular events (stroke or transient ischaemic attack (TIA)) in patients with patent foramen ovale (PFO) or atrial septal aneurysm (ASA) treated with different therapeutic regimens. We enrolled 86 patients aged 18-60 years with an unexplained ischaemic stroke or TIA referred to our inpatient department in the period May 1994-December 1999. Follow-up lasted until April 2003. Patients were excluded if the stroke or TIA was related to large-artery atherosclerosis, small artery occlusion, major cardiac sources of embolism or other uncommon causes. During a follow-up (mean+/-SD) of 64.1+/-28.8 months (range 8.1-105.6) a recurrent ischaemic cerebrovascular event occurred in 11/86 patients (12.8%) (5 TIA and 6 strokes). Eight events (4 TIA, 4 strokes) occurred in the 59 patients with PFO alone, three (1 TIA, 2 strokes) in the 21 with PFO plus ASA and none in the 6 patients with ASA alone. In the overall population the cumulative risk of recurrent stroke/TIA was 1.2% at 2 years, 5.5% at 4 years, 7.6% at 6 years and 23.6% at 8 years, and was similar in patients with PFO alone vs. patients with PFO plus ASA (9.0% vs. 6.1% at 6 years, 26.0% vs. 23.1% at 8 years; p0.05). Nine cerebral ischaemic events (4 TIA, 5 strokes) occurred in the 48 patients treated with antiplatelet drugs (7 in patients with PFO, 2 in patients with PFO plus ASA), and two (1 TIA, 1 stroke) in the 17 patients treated with oral anticoagulants (1 with PFO, 1 with PFO plus ASA). No events occurred in patients submitted to transcatheteral closure.