A novel risk score predicting 30-day hospital re-admission of patients with acute stroke by machine learning model.

BACKGROUND: The 30-day hospital re-admission rate is a quality measure of hospital care to monitor the efficiency of the healthcare system. The hospital re-admission of acute stroke (AS) patients is often associated with higher mortality rates, greater levels of disability and increased healthcare costs. The aim of our study was to identify predictors of unplanned 30-day hospital re-admissions after discharge of AS patients and define an early re-admission risk score (RRS). METHODS: This observational, retrospective study was performed on AS patients who were discharged between 2014 and 2019. Early re-admission predictors were identified by machine learning models. The performances of these models were assessed by receiver operating characteristic curve analysis. RESULTS: Of 7599 patients with AS, 3699 patients met the inclusion criteria, and 304 patients (8.22%) were re-admitted within 30 days from discharge. After identifying the predictors of early re-admission by logistic regression analysis, RRS was obtained and consisted of seven variables: hemoglobin level, atrial fibrillation, brain hemorrhage, discharge home, chronic obstructive pulmonary disease, one and more than one hospitalization in the previous year. The cohort of patients was then stratified into three risk categories: low (RRS = 0-1), medium (RRS = 2-3) and high (RRS >3) with re-admission rates of 5%, 8% and 14%, respectively. CONCLUSIONS: The identification of risk factors for early re-admission after AS and the elaboration of a score to stratify at discharge time the risk of re-admission can provide a tool for clinicians to plan a personalized follow-up and contain healthcare costs.

Prolonged Secondary Stroke Prevention with Edoxaban: A Long-Term Follow-Up of the SATES Study.

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.

Early neurological deterioration in patients with minor stroke due to isolated M2 occlusion undergoing medical management: a retrospective multicenter study.

BACKGROUND: Patients with minor stroke and M2 occlusion undergoing best medical management (BMM) may face early neurological deterioration (END) that can lead to poor long-term outcome. In case of END, rescue mechanical thrombectomy (rMT) seems beneficial. Our study aimed to define factors relevant to clinical outcome in patients undergoing BMM with the possibility of rMT on END, and find predictors of END. METHODS: Patients with M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score≤5 that received either BMM only or rMT on END after BMM were extracted from the databases of 16 comprehensive stroke centers. Clinical outcome measures were a 90-day modified Rankin Scale (mRS) score of 0-1 or 0-2, and occurrence of END. RESULTS: Among 10 169 consecutive patients with large vessel occlusion admitted between 2016 and 2021, 208 patients were available for analysis. END was reported in 87 patients that were therefore all subjected to rMT. In a logistic regression model, END (OR 3.386, 95% CI 1.428 to 8.032), baseline NIHSS score (OR 1.362, 95% CI 1.004 to 1.848) and a pre-event mRS score=1 (OR 3.226, 95% CI 1.229 to 8.465) were associated with unfavorable outcome. In patients with END, successful rMT was associated with favorable outcome (OR 4.549, 95% CI 1.098 to 18.851). Among baseline clinical and neuroradiological features, presence of atrial fibrillation was a predictor of END (OR 3.547, 95% CI 1.014 to 12.406). CONCLUSION: Patients with minor stroke due to M2 occlusion and atrial fibrillation should be closely monitored for possible worsening during BMM and, in this case, promptly considered for rMT.

Stroke and endocarditis: Reversing the point of view. A retrospective, cohort study.

STUDY OBJECTIVES: The primary objective of our study is to assess the endocarditis prevalence in patients admitted to the emergency department (ED) for a primary diagnosis of acute stroke (AS). Secondary objectives are the identification of early markers of endocarditis in AS patients and the analysis of the short-term outcome of this population. METHODS: In this observational, retrospective, cohort study we enrolled consecutive adult patients with a primary diagnosis of AS admitted to the Stroke Unit or to the Neurological Intensive Care Unit of our hospital who were then discharged with a diagnosis of endocarditis. These patients were then compared with age and sex-matched controls with a diagnosis of AS and atrial fibrillation. RESULTS: Endocarditis prevalence in patients admitted to the Stroke Unit or Neurological Intensive Care Unit with a primary diagnosis of AS is 1.0% (95% confidence interval 0.61-1.55). Fever on ED admission, concomitant cancer, low hemoglobin, low lymphocyte levels, a high neutrophils count and erythrocyte sedimentation levels could early differentiate among AS patients, those with endocarditis from those with atrial fibrillation. A moderate-to-severe valvular regurgitation is strongly suggestive of endocarditis. The short term-outcome is markedly worse in endocarditis patients compared to patients with atrial fibrillation, in terms of in-hospital mortality and discharge disability. CONCLUSIONS: Endocarditis prevalence in patients admitted for a primary diagnosis of AS is low, but this etiology leads to a poor outcome. Some laboratory, clinical-epidemiological and echocardiographic parameters may help the physician to early recognize this condition and, consequently, to promptly start an antibiotic therapy.

COVID-19 Vaccination Is Associated with a Better Outcome in Acute Ischemic Stroke Patients: A Retrospective Observational Study.

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.

Pupillometric findings in ATTRv patients and carriers: results from a single-centre experience.

INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRv) is a treatable multisystemic disease with great phenotypic heterogeneity. Among extra-neurological features, pupillary abnormalities have been reported, either related to amyloid deposition in the eye or to a progressive autonomic neuropathy. OBJECTIVE: To evaluate the role of automated pupillometry, a non-invasive and rapid test able to provide objective and reproducible data on pupil size and reactivity, as a marker of disease severity in late-onset ATTRv patients. PATIENTS AND METHODS: We performed automated pupillometry on a cohort of ATTRv patients and pre-symptomatic TTR mutation carriers and compared results to healthy controls. An exhaustive clinical and instrumental evaluation was performed on all enrolled subjects. RESULTS: A statistically significant difference in most pupillometry parameters was found in ATTRv patients as compared to both carriers and healthy controls. Moreover, in ATTRv patients, we found a significant correlation between many pupillometry findings and disease duration, as well as widely accepted clinical scales and investigations (NIS, Sudoscan from feet, and Norfolk QoL-DN questionnaire). CONCLUSIONS: We suggest pupillometry may play a role as a reliable and non-invasive biomarker to evaluate ATTRv disease severity and monitor its progression.

Th1/Th2 polarization of peripheral immune response in atherothrombotic and cardioembolic stroke: a prospective study.

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.

Autonomic Dysfunction during Acute SARS-CoV-2 Infection: A Systematic Review.

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.

Autonomic dysfunction in non-critically ill COVID-19 patients during the acute phase of disease: an observational, cross-sectional study.

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.

Cerebral edema in acute stroke: Effect of thrombolytic treatment.

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 n-IVT patients only between 24 and 72 h from the ischemic event (respectively 1.85cm3/h and 0.89cm3/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 acute stroke. Further studies are needed to define the molecular pathways involved in the genesis of CE in humans and to verify the efficacy of specific drugs.

Predicting Factors for Seizures after Cerebral Venous Thrombosis: A Retrospective Single Center Cohort Study.

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.

Instrumental Evaluation of COVID-19 Related Dysautonomia in Non-Critically-Ill Patients: An Observational, Cross-Sectional Study.

Coronavirus disease-19 (COVID-19) is a predominantly respiratory syndrome. Growing reports about a SARS-CoV-2 neurological involvement, including autonomic dysfunction (AD), have been reported, mostly in critically-ill patients, or in the long-COVID syndrome. In this observational, cross-sectional study, we investigated the prevalence of AD in 20 non-critically-ill COVID-19 patients (COVID+ group) in the acute phase of the disease through a composite instrumental evaluation consisting of Sudoscan, automated pupillometry, heart rate variability (HRV), and pulse transit time (PTT). All the parameters were compared to a control group of 20 healthy volunteers (COVID- group). COVID+ group presented higher values of pupillary dilatation velocities, and baseline pupil diameter than COVID- subjects. Moreover, COVID+ patients presented a higher incidence of feet sudomotor dysfunction than COVID- group. No significant differences emerged in HRV and PTT parameters between groups. In this study we observed the occurrence of autonomic dysfunction in the early stage of the disease.

Ixekizumab exposure associated with myelitis: A case report and a literature review.

We describe a case of a 28-year-old man who developed a cervical myelitis while exposed to ixekizumab (IL-17 inhibitor) for psoriatic arthritis. Spinal MRI showed a T2 hyperintense lesion at the C4-C5 level while brain MRI was unspecific. Oligoclonal bands were absent and extensive screening for autoimmunity was negative. Rechallenge with ixekizumab was positive corroborating a relation between drug exposure and the neurological event. To the best of our knowledge, this is the first case of CNS inflammatory adverse event associated with ixekizumab. We also provide a review of case reports of demyelinating disorders associated with the use of biologic drugs for the treatment of psoriasis and psoriatic arthritis.

COVID-19 and stroke: from the cases to the causes.

During COVID-19 pandemic, a wide variety of stroke typologies have been described in patients affected by SARS-CoV-2. Investigating the case reports of acute stroke in COVID-19 patients, published since the beginning of the pandemic, we tried to trace the pathogenic mechanisms of stroke during SARS-CoV-2 infection. We conducted a systematic review analyzing demographic data, cerebrovascular risk factors, NIHSS score, vascular territory involvement and laboratory findings of 168 patients described in 89 studies, from a pool of 1243 records. Based on our results, we have identified different stroke profiles: (1) cerebral large vessel disease (CLVD) profile with a low disability, simultaneous onset of COVID-19 and stroke symptoms, good outcome and low serum levels of D-dimer and CRP; (2) intracranial bleeding (IB) profile with high disability, poor outcome and low levels of serum markers of inflammation and coagulopathy; (3) CLVD profile with a short time-lapse between COVID-19 symptoms and stroke onset, high neurological disability and very high systemic inflammatory markers; (4) multiple thrombo-embolic disease (MTED) profile with older patients, many comorbidities, disabling stroke, poor outcome, evident alteration of coagulation tests and high serum levels of both D-dimer and CRP. We therefore summarized these different profiles in a spectrum similar to that of visible light, where the violet-blue band included IB and CSVD with low inflammation and prothrombotic activity, the green-yellow band included CLVD with high inflammation and moderate prothrombotic activity and the orange-red band for MTED with moderate-high levels of inflammation and very high prothrombotic activity.

Effect of the COVID-19 pandemic and the lockdown measures on the local stroke network.

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.

Stroke and COVID19: Not only a large-vessel disease.

Recent evidence has underlined the association between large-vessel stroke and COVID-19, probably due to a proinflammatory and prothrombotic microenvironment induced by SARS-CoV-2. Here, we report the case of a young fit woman affected by COVID-19 without any flu-like symptom, who suffered from speech disorder and left hemiparesis. Brain magnetic resonance evidenced two small acute brain infarctions in right perirolandic cortex without signs of previous ischemic lesions and hemorrhagic infarction. Diagnostic workup excluded cardiac embolic sources, acquired and inherited thrombophilia or autoimmune diseases. Two positive nasopharyngeal swab tests and high titers of serum specific IgA/IgM confirmed COVID-19 diagnosis. In our case stroke seems to be the only manifestation of SARS-COV-2 infection. Therefore the hypothesis of an underlying viral infection, as COVID-19, should be investigated in all the cases of small vessel cryptogenic stroke.

An Italian Neurology Outpatient Clinic Facing SARS-CoV-2 Pandemic: Data From 2,167 Patients.

Objective: Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients. Methods: Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions. Results: Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms. Conclusions: In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.

Prospective Observational Study of Safety of Early Treatment with Edoxaban in Patients with Ischemic Stroke and Atrial Fibrillation (SATES Study).

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.