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Background: Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core. Aim: The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ≤ 5, undergoing MT. Material and methods: The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ≤ 5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. Statistical analysis used a logistic regression model and random forest algorithm. Results: 408 patients were available for analysis. In multivariate model, among baseline features, lower age (OR 0.962, 95% CI 0.943-0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR 0.911, 95% CI 0.862-0.963) were associated with the mRS score 0-2. Involvement of the M2 (OR 0.398, 95% CI 0.206-0.770) or M4 (OR 0.496, 95% CI 0.260-0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2 and M1 can have a negative impact. Conclusion: Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT.

Background and purposePost-stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS).MethodsWe enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months.ResultsNone of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs.ConclusionPost-stroke movement disorders are not uncommon in long-term follow-up of successfully reperfused AIS. Follow-up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge.

Background: There is a growing body of evidence suggesting a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). The primary objective of this study is to evaluate the association between OSA and AF in acute ischemic stroke. The secondary objective is to describe the clinical features of patients with acute ischemic stroke and concomitant OSA. Methods: We enrolled consecutive patients with acute ischemic stroke. All patients underwent full-night cardiorespiratory polygraphy. To determine if there is an association between AF and OSA, we compared the observed frequency of this association with the expected frequency from a random co-occurrence of the two conditions. Subsequently, patients with and without OSA were compared. Results: A total of 174 patients were enrolled (mean age 67.3 ± 11.6 years; 95 males). OSA and AF were present in 89 and 55 patients, respectively. The association OSA + AF was observed in 33/174 cases, which was not statistically different compared to the expected co-occurrence of the two conditions. Patients with OSA showed a higher neck circumference and body mass index, a higher prevalence of hypertension and dysphagia, and a higher number of central apneas/hypoapneas. In the multivariate analysis, dysphagia and hypertension were independent predictors of OSA. A positive correlation was observed between OSA severity, BMI, and neck circumference. The number of central apneas/hypoapneas was positively correlated with stroke severity. Conclusions: Our data suggest that OSA and AF are highly prevalent but not associated in acute stroke. Our findings support the hypothesis that OSA acts as an independent risk factor for stroke.

Background: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. Methods: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. Results: Sixty-three subjects (median age 81.0 (73.5-88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 +/- 0.7 years (range: 3.2-5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment.

BackgroundThe aim of our study was to find predictors of parenchymal hematoma (PH) and clinical outcome after mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) and baseline large infarct.MethodsThe databases of 16 stroke centers were retrospectively screened for patients with anterior circulation LVO and baseline Alberta Stroke Program Early CT Score (ASPECTS) <= 5 that received MT. Procedural parameters, including the number of passes during first and second technique of MT, were recorded. Outcome measures were occurrence of PH type 2 and any type of PH after MT, and the 90-day modified Rankin Scale (mRS) score of 0-3 and 0-2.ResultsIn total, 408 patients were available for analysis. A higher number of passes in the second technique was predictive of PH type 2 (odds ratio (OR) - 3.204, 95% confidence interval (CI) 1.140 to 9.005), whereas procedure conducted under general anesthesia was associated with lower risk (OR 0.127, 95% CI 0.002 to 0.808). The modified thrombolysis in cerebral infarction grade 2c-3 was associated with the mRS score 0-3 (OR 3.373, 95% CI 1.891 to 6.017), whereas occurrence of PH type 2 was predictive of unfavorable outcome (OR 0.221, 95% CI 0.063 to 0.773). Similar results were found for the mRS score 0-2 outcome measure.ConclusionIn patients with large ischemic core, a higher number of passes during MT and procedure not conducted under general anesthesia are associated with increased rate of PH type 2, that negatively impact the clinical outcome. Our data outline a delicate balance between the need of a complete recanalization and the risk of PH following MT.

Introduction Heart surgery can be associated with adverse ischemic brain events. Case report Here, we describe two patients who presented extensive infarction of the corpus callosum and of other brain watershed areas following coronary artery bypass grafting (CABG) on extracorporeal circulation (ECC). Discussion Infarction of the corpus callosum is an extremely rare condition due to its abundant blood supply. Our findings are noteworthy since they diverge from classical brain watershed infarcts and from other cases of corpus callosum involvement. This suggests that in some cases, CABG surgery on ECC may be associated to a profound impairment of intracerebral circulation. However, it is also possible that the corpus callosum is particularly vulnerable to yet unknown metabolic modifications connected to ECC. Conclusions Further studies are needed in order to investigate the complex response of brain circulation and metabolism during heart surgery with ECC.

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Background: Seizures are a common complication of cerebral venous thrombosis. In this study, we intended to define clinical and neuroradiological factors associated with early and late seizures and predictors for seizure recurrence. Methods: The database of our high-volume tertiary stroke center was screened for patients diagnosed with cerebral venous thrombosis between April 2006 and July 2021. Demographics, clinical, imaging, and instrumental data were collected. Results: Out of a total of 80 patients, 30 had seizures, either within the first week after onset (22 patients) or after (8 patients). Speech impairment and intracerebral bleeding were statistically associated with seizures in univariate analysis, but in a logistic regression model, only brain damage with hemorrhagic infarct and/or presence of brain hematoma [OR 6.051; 95% CI 1.881−19.468] (p = 0.003) were predicting factors for seizures. Late seizures were significantly more frequent in younger age [OR 0.864; 95% CI 0.763−0.978] (p = 0.020). Early seizures resulted as protective factors for recurrence; an altered state of consciousness at baseline and late seizures resulted as predictive factors for relapses (0.0% vs. 81.0%, p = 0.005, and 100.0% vs. 19.0%, p < 0.005, respectively). Conclusions: Our study confirms brain bleeding as the strongest risk factor for seizures after cerebral venous thrombosis. Recurrence is unusual after early seizures, while the presence of late seizures seems to raise the risk of recurrence.

Although autonomic dysfunction (AD) after the recovery from Coronavirus disease 2019 (COVID-19) has been thoroughly described, few data are available regarding the involvement of the autonomic nervous system (ANS) during the acute phase of SARS-CoV-2 infection. The primary aim of this review was to summarize current knowledge regarding the AD occurring during acute COVID-19. Secondarily, we aimed to clarify the prognostic value of ANS involvement and the role of autonomic parameters in predicting SARS-CoV-2 infection. According to the PRISMA guidelines, we performed a systematic review across Scopus and PubMed databases, resulting in 1585 records. The records check and the analysis of included reports' references allowed us to include 22 articles. The studies were widely heterogeneous for study population, dysautonomia assessment, and COVID-19 severity. Heart rate variability was the tool most frequently chosen to analyze autonomic parameters, followed by automated pupillometry. Most studies found ANS involvement during acute COVID-19, and AD was often related to a worse outcome. Further studies are needed to clarify the role of autonomic parameters in predicting SARS-CoV-2 infection. The evidence emerging from this review suggests that a complex autonomic nervous system imbalance is a prominent feature of acute COVID-19, often leading to a poor prognosis.

Background: Seizures are a common complication of cerebral venous thrombosis. In this study, we intended to define clinical and neuroradiological factors associated with early and late seizures and predictors for seizure recurrence. Methods: The database of our high-volume tertiary stroke center was screened for patients diagnosed with cerebral venous thrombosis between April 2006 and July 2021. Demographics, clinical, imaging, and instrumental data were collected. Results: Out of a total of 80 patients, 30 had seizures, either within the first week after onset (22 patients) or after (8 patients). Speech impairment and intracerebral bleeding were statistically associated with seizures in univariate analysis, but in a logistic regression model, only brain damage with hemorrhagic infarct and/or presence of brain hematoma [OR 6.051; 95% CI 1.881-19.468] (p = 0.003) were predicting factors for seizures. Late seizures were significantly more frequent in younger age [OR 0.864; 95% CI 0.763-0.978] (p = 0.020). Early seizures resulted as protective factors for recurrence; an altered state of consciousness at baseline and late seizures resulted as predictive factors for relapses (0.0% vs. 81.0%, p = 0.005, and 100.0% vs. 19.0%, p < 0.005, respectively). Conclusions: Our study confirms brain bleeding as the strongest risk factor for seizures after cerebral venous thrombosis. Recurrence is unusual after early seizures, while the presence of late seizures seems to raise the risk of recurrence.

Purpose of Review To elucidate the interconnection between sleep and stroke. Recent Findings Growing data support a bidirectional relationship between stroke and sleep. In particular, there is strong evidence that sleep-disordered breathing plays a pivotal role as risk factor and concur to worsening functional outcome. Conversely, for others sleep disorders (e.g., insomnia, restless legs syndrome, periodic limb movements of sleep, REM sleep behavior disorder), the evidence is weak. Moreover, sleep disturbances are highly prevalent also in chronic stroke and concur to worsening quality of life of patients. Promising novel technologies will probably allow, in a near future, to guarantee a screening of commonest sleep disturbances in a larger proportion of patients with stroke. Sleep assessment and management should enter in the routinary evaluation of stroke patients, of both acute and chronic phase. Future research should focus on the efficacy of specific sleep intervention as a therapeutic option for stroke patients.

Background The purpose of this study was to evaluate the effectiveness of mechanical thrombectomy (MT) in patients with isolated M2 occlusion and minor symptoms and identify possible baseline predictors of clinical outcome. Methods The databases of 16 high-volume stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score <= 5 who received either early MT (eMT) or best medical management (BMM) with the possibility of rescue MT (rMT) on early neurological worsening. Because our patients were not randomized, we used propensity score matching (PSM) to estimate the treatment effect of eMT compared with the BMM/rMT. The primary clinical outcome measure was a 90-day modified Rankin Scale score of 0-1. Results 388 patients were initially selected and, after PSM, 100 pairs of patients receiving eMT or BMM/rMT were available for analysis. We found no significant differences in clinical outcome and in safety measures between patients receiving eMT or BMM/rMT. Similar results were also observed after comparison between eMT and rMT. Concerning baseline predicting factors of outcome, the involvement of the M2 inferior branch was associated with a favorable outcome. Conclusion Our multicenter retrospective analysis has shown no benefit of eMT in minor stroke patients with isolated M2 occlusion over a more conservative therapeutic approach. Although our results must be viewed with caution, in these patients it appears reasonable to consider BMM as the first option and rMT in the presence of early neurological deterioration.

Cerebral edema (CED) is a common complication of ischemic stroke in Intensive Care Unit. Although frequently observed in patients undergoing intravenous thrombolytic (IVT) treatment, the pathogenic role of recombinant tissue plasminogen activator (rtPA) in CED induction has not yet been definitively clarified. The aim of our study is to verify the relationship between CED and rtPA in patients affected by acute ischemic stroke, without reperfusion signs, evaluating the CED growth rate in the first week after stroke onset. In this single-center, retrospective observational study, we included all consecutive patients with acute stroke undergone multi parameter monitoring of vital signs in the sub-intensive care Unit. We included both patients undergoing systemic IVT and standard medical treatment (n-IVT) with the following time of CT scan: within 4.5 h onset, 24 +/- 12 h, 72 +/- 24 h and 120 +/- 24 h from the stroke onset. Of 1753 with acute ischemic stroke patients screened, 810 patients were included in the study (218 IVT and 592 n-IVT). No significant difference was observed at baseline in age, gender, NIHSS score or infarcted area, while hemorrhagic transformation rate was significantly higher in IVT than in n-IVT group. We observed a significant increase of CED growth rate in IVT patients compared to nIVT patients only between 24 and 72 h from the ischemic event (respectively 1.85cm(3)/h and 0.89cm(3)/h; p = 0.031) regardless of the presence of HT. No significant difference was observed in growth rate between 3 and 5 days following rtPA administration or in overall growth rate. Although the pathogenetic mechanism of rtPA determining CED remains uncertain, our data suggests rtPA can act as a "trigger " of edema onset and progression. Therefore, drugs interfering with specific molecular pathways, such as kallikrein-kinin cascade, could constitute an effective strategy to reduce the risk of development and progression of rtPA-related cerebral edema in patients with a

Introduction Evidence is emerging about an extra-pulmonary involvement of SARS-CoV-2, including the nervous system. Autonomic dysfunction in patients recovering from acute coronavirus disease 2019 (COVID-19) has been recently described. Dysautonomic symptoms have been reported in the acute phase of the disease, but clear evidence is lacking, especially in the non-critical forms of the infection. Objective The aim of this study is to assess the prevalence of dysautonomia in acute, non-critically ill COVID-19 patients. Methods In this observational, cross-sectional study, we compared 38 non-critically ill patients with acute COVID-19 (COVID + group) to 38 healthy volunteers (COVID - group) in order to assess the prevalence of signs and symptoms of dysautonomia through the administration of the composite autonomic symptom score 31 (COMPASS-31) and an active standing test. Comparisons between groups were performed by means of both univariate and multivariate analyses. Results The prevalence of orthostatic hypotension was significantly higher in the COVID + group. Higher total scores of COMPASS-31 were observed in the COVID + group than controls. Significant differences between groups emerged in the secretomotor, orthostatic intolerance, and gastrointestinal COMPASS-31 domains. All these results maintained the statistical significance after the adjustment for concomitant drugs with a known effect on the autonomic nervous system assumed by the study participants, except for the differences in the gastrointestinal domain of COMPASS-31. Conclusion Our results suggest that an autonomic dysfunction could be an early manifestation of COVID-19, even in the contest of mild forms of the infection.

Background: Seizures are a common complication of cerebral venous thrombosis. In this study, we intended to define clinical and neuroradiological factors associated with early and late seizures and predictors for seizure recurrence. Methods: The database of our high-volume tertiary stroke center was screened for patients diagnosed with cerebral venous thrombosis between April 2006 and July 2021. Demographics, clinical, imaging, and instrumental data were collected. Results: Out of a total of 80 patients, 30 had seizures, either within the first week after onset (22 patients) or after (8 patients). Speech impairment and intracerebral bleeding were statistically associated with seizures in univariate analysis, but in a logistic regression model, only brain damage with hemorrhagic infarct and/or presence of brain hematoma [OR 6.051; 95% CI 1.881-19.468] (p = 0.003) were predicting factors for seizures. Late seizures were significantly more frequent in younger age [OR 0.864; 95% CI 0.763-0.978] (p = 0.020). Early seizures resulted as protective factors for recurrence; an altered state of consciousness at baseline and late seizures resulted as predictive factors for relapses (0.0% vs. 81.0%, p = 0.005, and 100.0% vs. 19.0%, p < 0.005, respectively). Conclusions: Our study confirms brain bleeding as the strongest risk factor for seizures after cerebral venous thrombosis. Recurrence is unusual after early seizures, while the presence of late seizures seems to raise the risk of recurrence.

Introduction Delirium is an acute fluctuating disorder of attention and awareness, which often complicates the clinical course of several conditions, including acute stroke. The aim of the present study was to determine whether delirium occurrence impacts the outcome of patients with acute stroke. Methods The study design is single center, prospective, observational. We consecutively enrolled patients admitted to the stroke unit from April to October 2020. Inclusion criteria were age >= 18 years and diagnosis of acute stroke. Exclusion criteria were stroke mimics, coma, and terminal conditions. All patients were screened for delirium upon admission, within 72 h, and whenever symptoms suggesting delirium occurred by means of the Confusion Assessment Method for Intensive Care Unit and the Richmond Agitation Sedation Scale. Outcomes were evaluated with the 90-days modified Rankin Scale (mRS) by telephone interview. Results The final study cohort consisted of 103 patients (62 men; median age 75 years, interquartile range 63-81). Thirty-one patients (30%) developed delirium. In the multivariate ordinal logistic regression, patients with delirium had higher mRS scores at 3 months (DLR + : mRS = 4 (3-6); DLR-: mRS = 1 (1-3); adjusted odds ratio = 4.83; CI = 1.88-12.35; p = 0.006). Delirium was a risk factor for death (mRS = 6) in the univariate logistic regression (OR 4.5, CI = 1.44-14.07; p = 0.010), but not in the adjusted analysis (OR 3.45; CI = 0.66-17.95; p = 0.142). Survival time during 90-days follow-up was shorter in the delirium group (Log Rank chi(2) 3.89; p = 0.048). Conclusion Delirium negatively impacts the prognosis of patients with acute stroke. Patients with post-stroke delirium have a worse functional outcome and a shorter survival.

Sleep disorders are frequent in acute stroke. The Richards-Campbell Sleep Questionnaire (RCSQ) is a validated scale for the sleep assessment in intensive care unit. The aim of the present study is to validate RCSQ for use in patients with acute stroke. We performed a validation study by comparing the RCSQ with polysomnography (PSG), the standardized measure of sleep. Inclusion criteria were age >= 18 years and a radiologically confirmed diagnosis of stroke. Exclusion criteria were global aphasia, extreme severity of clinical conditions and inability to attend PSG. All patients underwent PSG in a stroke unit, the day after a subjective sleep assessment by means of the RCSQ. The RCSQ was compared with PSG parameters to assess the degree of concordance of the two measures. The cohort consisted of 36 patients. Mean RCSQ score was 61.5 +/- 24.8. The total score of the RCSQ showed a good degree of concordance with the sleep efficiency index of PSG. Accuracy of the RCSQ was 70%, sensitivity 71% and specificity 68%. The RCSQ is a good tool for screening the sleep quality in the setting of a stroke unit. Therefore, it could be useful to select the patients who might beneficiate from an instrumental sleep evaluation.

Background: It is unclear whether and how COVID-19 vaccination may affect the outcome of patients with acute ischemic stroke (AIS). We investigated this potential association in a retrospective study by comparing previously vaccinated (VAX) versus unvaccinated (NoVAX) stroke patients. Methods: We collected clinical reports for all consecutive AIS patients admitted to our hospital and evaluated the outcome predictors in VAX and NoVAX groups. Adjustments were made for possible confounders in multivariable logistic regression analysis, and adjusted hazard ratios were calculated. Results: A total of 466 AIS patients (287 VAX and 179 NoVAX) were included in this study. The NIHSS score at discharge and mRS score at a 3-month follow-up visit were significantly lower in VAX patients compared to NoVAX patients (p < 0.001). Good outcomes (mRS 0-2) were significantly associated with COVID-19 vaccination before AIS (adjusted hazard ratio, 0.400 [95% CI = 0.216-0.741]). Conclusions: The observation that COVID-19 vaccination can influence the outcome of AIS provides support for further studies investigating the role of immunity in ischemic brain damage.

Compelling evidence suggest a key role of immune system in the development and progression of ischemic stroke. Although the balance between proinflammatory CD4 + T helper (Th)-1 lymphocytes, expressing T-bet transcription factor, and anti-inflammatory Th2 cells expressing GATA3 seems to influence the outcome in experimental stroke, the role of peripheral immune response in acute stroke patients is poorly understood. We aimed to evaluate the peripheral Th1/Th2 balance in acute atherothrombotic (ATHS) and cardioembolic stroke (CES) patients and in age- and sex-matched healthy subjects. Using flow cytometry, we analyzed the percentage of CD4 + T-bet + T cells and CD4 + GATA3 + T cells from peripheral blood of ATHS and CES patients (2,4 and 7 days after stroke onset). Patients and controls were screened for infectious conditions, autoimmune, inflammatory, or cancerous diseases. On day 2 circulating CD4 + T-bet + T cells were significantly higher in stroke patients compared to controls, and in ATHS compared to CES and controls. On day 7, we observed a significant increase of CD4 + T-bet + T cells in both ATHS and CES patients compared to baseline. No difference was observed in circulating CD4 + GATA3 + T cells among ATHS, CES patients, and controls. These data suggest that circulating CD4 + T-bet + T cells could be useful marker indicating atherothrombotic genesis of stroke and provide new insight into the peripheral adaptive immune response in acute stroke.

Introduction: Heart surgery can be associated with adverse ischemic brain events. Case report: Here, we describe two patients who presented extensive infarction of the corpus callosum and of other brain watershed areas following coronary artery bypass grafting (CABG) on extracorporeal circulation (ECC). Discussion: Infarction of the corpus callosum is an extremely rare condition due to its abundant blood supply. Our findings are noteworthy since they diverge from classical brain watershed infarcts and from other cases of corpus callosum involvement. This suggests that in some cases, CABG surgery on ECC may be associated to a profound impairment of intracerebral circulation. However, it is also possible that the corpus callosum is particularly vulnerable to yet unknown metabolic modifications connected to ECC. Conclusions: Further studies are needed in order to investigate the complex response of brain circulation and metabolism during heart surgery with ECC.

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Introduction: Clot features along with patients' clinical features may influence thrombus compactness predisposing at distal embolization during thrombectomy. The aim of this study was to evaluate thrombus features assessed by radiological and histopathological analysis along with patient-related features to predict distal embolization during thrombectomy.Methods: We performed a retrospective analysis of a prospectively maintained dataset of a tertiary stroke center inclusive of all cases of endovascular treatment for acute ischemic stroke involving anterior circulation occlusion. All patients underwent head and neck CT-angiography (CTA) at baseline. Patients were enrolled if thrombus material was suitable for histopathologic analyses.Results: A total of 327 patients underwent mechanical thrombectomy between March 2017 and May 2020. Among them, 133 (40.7%) had thrombus material suitable for histopathological analysis but 11 patients were excluded due to posterior circulation occlusion. A total of 122 patients were included in the analysis. A distal embolism was documented in 27 patients (28.4%). Multivariable analysis with distal embolism as dependent variable showed an adjusted OR of 2.64 (95%CI: 0.9-7.73; p-value: 0.08) for anticoagulant therapy, an adjusted OR of 1.38 (95%CI: 1.01-1.91; p-value 0.05) each 5-mm increasing of thrombus length at CTA. No association was found with age, sex, thrombolysis and first thrombectomy technique used.Conclusion: The combined effect of anticoagulant therapy and thrombus length may have a potentially harmful effect on reperfusion during mechanical recanalization, causing distal embolization and this aspect should be taken into account in patient's risk assessment and when planning treatment strategy.

Background and Purpose The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and baseline mild neurological symptoms remains unclear. The purpose of this study was to evaluate the effectiveness of MT in this subgroup of patients. Methods The databases of 9 high-volume Italian stroke centers were retrospectively screened for patients with LVO in the anterior circulation and a baseline National Institute of Health Stroke Scale (NIHSS) score <= 5 that received either immediate MT or best medical management (BMM) with the possibility of rescue MT upon neurological worsening. Primary outcome measure was a modified Rankin Scale score of 0-1 at 90 days. Propensity score matching (PSM) analysis was used to estimate the treatment effect of immediate MT compared to BMM/rescue MT. Results Two hundred and seventy-two patients received immediate MT (MT group). The BMM/rescue MT group included 41 patients. The primary outcome was achieved in 78.6% (n = 246) of overall patients, with a higher proportion in the MT group (80.5% vs. 65.9%, p = 0.03) in unadjusted analysis. After PSM, patients in the MT group had a 19.5% higher chance of excellent outcome at 90 days compared to the BMM/Rescue MT group with a similar risk of death from any cause. Conclusions Our experience is in favor of a potential benefit of MT also in patients with LVO and a NIHSS score <= 5 at the time of groin puncture. Nonetheless, this issue waits for a clear-cut recommendation in a dedicated clinical trial.

We sought to verify the benefit of mechanical thrombectomy in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation and low National Institute of Health stroke scale score at presentation. The prospective database of our stroke center was screened for patients with acute ischemic stroke due to large vessel occlusion and a baseline National Institute of Health stroke scale score <= 5 that had undergone mechanical thrombectomy. Outcome measures were the modified Rankin Scale (mRS) score at 90 days, brain bleeding events and death at 90 days. Out of 459 patients, 17 (12 females, mean age 70 +/- 14 years) with occlusion of M1 or M2 segment of middle cerebral artery and baseline National Institute of Health stroke scale score <= 5 underwent mechanical thrombectomy. Eight patients (47%) were treated within 6 hours from the onset, 5 (29%) were treated beyond 6 hours, and 4 (24%) were wakeup strokes. Effective mechanical thrombectomy was achieved in 16 patients (94%) and associated with excellent functional outcomes at 3 months (mRS 0-1) in 13 (76%). The asymptomatic brain-bleeding event was observed in one patient 4 days after effective mechanical thrombectomy concerning safety issues. One patient died 1 month after mechanical thrombectomy of a cause unrelated to stroke. Our findings favor a potential benefit of mechanical thrombectomy in patients with stroke due to large vessel occlusion and low National Institute of Health stroke scale score at presentation. These patients may also benefit from a prolonged time window for treatment.

Introduction The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. Methods This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020-4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. Results A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. Discussion Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers.

New direct oral anticoagulants are recommended for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). However, no data are available regarding the optimal time to start oral anticoagulation after acute stroke. The aim of our study was to evaluate the occurrence of symptomatic bleedings within 90 days from acute cardioembolic stroke in patients who received early treatment with Edoxaban. The study was conducted according to an observational prospective uncontrolled design. Secondary endpoints were the incidence of major bleeding (MB), hemorrhagic transformation within the first week of Edoxaban treatment, minor bleeding, and recurrent stroke. We included patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) >= 6, NVAF, no previous treatment with any other anticoagulant, preserved swallowing function. Patients with estimated Glomerular Filtration Rate < 50 mL/min, body weight < 60 kg, receiving cyclosporine, dronedarone, erythromycin, ketoconazole, or previous treatment with any other anticoagulant were excluded. We enrolled 75 elderly patients with moderate disability. We did not observe any symptomatic intracranial bleeding or recurrent stroke after 3 months of treatment with early administration of Edoxaban, while two gastrointestinal MB, and 11 minor bleedings were reported. Asymptomatic bleeding was evaluated with a brain Magnetic Resonance Imaging performed 5 days after starting anticoagulant treatment with Edoxaban. Specifically, we observed small petechiae in 12% of the patients, confluent petechiae in 6.6% of the patients, and small hematoma of the infarcted area in 2.7% of the patients. No intralesional hematoma or hemorrhagic lesion outside the infarcted area were observed. According to our data, the early use of Edoxaban seems to be safe in patients after cardioembolic stroke. However, due to the small size of the study sample, and the short follow-up period, further studies are needed.

Objective To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke. Methods This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019. Results The clinical reports of patients eligible for the study were 52 in 2020 (71.6 +/- 12.2 years) and 41 in 2019 (73.7 +/- 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min,p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13,p = 0.033), a non-significant increase of thrombectomy (15 vs 9,p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min,p = 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted. Conclusions Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances.

Although thrombectomy is beneficial for most stroke patients with large vessel occlusion (LVO), it has added new issues in acute management due to intensive care support. In this prospective cohort study, we described the patients admitted to our neuro-intensive care unit (NICU) after thrombectomy in order to assess factors linked to functional outcomes. The outcome was independency assessed for stroke patients consecutively admitted to NICU for an ischemic stroke due to LVO of the anterior cerebral circulation that underwent intra-arterial mechanical thrombectomy (IAMT), either in combination with intravenous thrombolysis (IVT) in eligible patients or alone in patients with contraindications for IVT. Overall, 158 patients were enrolled. IVT (odds ratio (OR), 3.78; 95% confidence interval (CI), 1.20-11.90; p = 0.023) and early naso-gastric tube removal (OR, 3.32; 95% CI, 1.04-10.59 p = 0.042) were associated with good outcomes, whereas a high baseline National Institutes of Health Stroke Scale (NIHSS) score (OR, 0.72 for each point of increase; 95% CI, 0.61-0.85; p < 0.001) was a predictor of poor outcomes at 3 months. Older age (OR, 0.95 for each year of increase; 95% CI, 0.92-0.99; p = 0.020) and hemorrhagic transformation (OR, 0.31; 95% CI, 0.11-0.84; p = 0.022) were predictors of poor outcomes after IAMT, whereas a modified Treatment in Cerebral Infarction (mTICI) score of 2b/3 was a predictor of good outcomes (OR, 7.86; 95% CI, 1.65-37.39; p = 0.010) at 6 months. Our results show that acute stroke patients with LVO who require NICU management soon after IAMT may show specific clinical factors influencing short- and long-term neurologic independency.

Background: Obstructive sleep apnea (OSA) and dysphagia are common in acute stroke and are both associated with increased risk of complications and worse prognosis. The aims of the present study were (1) to evaluate the prevalence of OSA and dysphagia in patients with acute, first-ever, ischemic stroke; (2) to investigate their clinical correlates; and (3) to verify if these conditions are associated in acute ischemic stroke. Methods: We enrolled a cohort of 140 consecutive patients with acute-onset (<48 hours), first-ever ischemic stroke. Computed tomography (CT) and magnetic resonance imaging scans confirmed the diagnosis. Neurological deficit was measured using the National Institutes of Health Stroke Scale (NIHSS) by examiners trained and certified in the use of this scale. Patients underwent a clinical evaluation of dysphagia (Gugging Swallowing Screen) and a cardiorespiratory sleep study to evaluate the presence of OSA. Results: There are 72 patients (51.4%) with obstructive sleep apnea (OSA+), and there are 81 patients (57.8%) with dysphagia (Dys+). OSA+ patients were significantly older (P =.046) and had greater body mass index (BMI) (P =.002), neck circumference (P =.001), presence of diabetes (P =.013), and hypertension (P <.001). Dys+ patients had greater NIHSS (P <.001), lower Alberta Stroke Programme Early CT Score (P <.001), with greater BMI (P =.030). The association of OSA and dysphagia was greater than that expected based on the prevalence of each condition in acute stroke (P <.001). Conclusions: OSA and dysphagia are associated in first-ever, acute ischemic stroke.

The term hereditary inclusion-body myopathies (HIBMs) defines a group of rare muscle disorders with autosomal recessive or dominant inheritance and presence of muscle fibers with rimmed vacuoles and collection of cytoplasmic or nuclear 15-21. nm diameter tubulofilaments as revealed by muscle biopsy. The most common form of HIBM is due to mutations of the GNE gene that codes for a rate-limiting enzyme in the sialic acid biosynthetic pathway. This results in abnormal sialylation of glycoproteins that possibly leads to muscle fiber degeneration. Mutations of the valosin containing protein are instead responsible for hereditary inclusion-body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD), with these three phenotypic features having a variable penetrance. IBMPFD probably represents a disorder of abnormal cellular trafficking of proteins and maturation of the autophagosome. HIBM with congenital joint contractures and external ophthalmoplegia is due to mutations of the Myosin Heavy Chain IIa gene that exerts a pathogenic effect through interference with filament assembly or functional defects in ATPase activity. This review illustrates the clinical and pathologic characteristics of HIBMs and the main clues available to date concerning the possible pathogenic mechanisms and therapeutic perspectives of these disorders. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

Neurofibromatosis type 1 (NF1) is a heterogeneous, common, neurocutaneous disorder presenting different complications during a life span, including cerebrovascular dysplasia. To our knowledge this is the first reported case of NF1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke. We describe a 57-year-old man with NF1 who presented an acute onset right-sided facial palsy and hemiplegia, dysarthria, and gait imbalance. Magnetic resonance imaging showed an acute left paramedian pontine infarct and a hypoplastic right vertebral artery. Brain Computed Tomography Angiography revealed the occurrence of vertebrobasilar dolichoectasia. Co-occurrence of VBD and NF1 might not be merely casual and it may significantly heighten the mortality rate in this multisystem disorder. We suggest a possible role of VBD in the genesis of our patient's clinical-radiological features and prompt the early detection of asymptomatic arteriopathy in individuals with NF1 in order to ameliorate patients' quality of life and life expectancy