MARKERS BIOLOGICI DI RICANALIZZAZIONE E DI EFFICACIA CLINICA DEL TRATTAMENTO CON r-tPA NELL'ICTUS CEREBRALE ISCHEMICO ACUTO

L\u2019ictus cerebrale \ue8 una delle maggiori cause di morte e disabilit\ue0. Ad oggi, l\u2019unico trattamento approvato per l\u2019ictus ischemico \ue8 quello trombolitico con r-tPA. Nel singolo paziente, numerosi sono i fattori che concomitano nel determinare l\u2019outcome dopo tale terapia. L'obiettivo della presente tesi \ue8 di determinare i principali biomarcatori del sistema emocoagulativo, fibrinolitico e infiammatori, allo scopo di porre le basi per una rapida predizione dell\u2019outcome post-fibrinolisi e di un suo miglioramento attraverso una gestione mirata e commisurata al singolo paziente

May lamotrigine be an alternative to topiramate in the prevention of migraine with aura? Results of a retrospective study

Evidence suggests that lamotrigine could be effective in reducing aura frequency and duration. However, studies comparing lamotrigine to other, first-line prophylactic agents solely involving patients suffering from migraine with aura are still lacking. The aim of this study was to compare the efficacy of lamotrigine and topiramate for the preventive treatment of migraine with aura

Odontorizectomie: un case series a 12 anni

The study evaluates whether root amputation may be considered a valid alternative to or support for implant treatment in the long term. The series comprised 20 patients, observed from 1997 to 2007; all cases were of mandibular molars in which the distal root was preserved. Causes of the operation were: failure of orthograde therapy with fracture of mesial root, perforation of pulp chamber floor and internal-external mesial root resorption. After 10 years, the success rate was 70%. The encouraging results indicate that root amputation is still an effective method. From both biologic and economic standpoints, it may be considered as an alternative to and/or support for more expensive treatments, but must be employed following precise clinical indications

development tools usage inside out

The software engineering community is continuously producing tools to tackle software construction problems. This paper presents a research study to identify which tools, artifacts, and commands developers use during task solving and how one can design software that can suggest and convince the developer to use specific software construction techniques. We want to understand under which conditions developers accept suggestions for a more efficient and effective usage of the available instruments, and if observed usage patterns correlate with observable improvements in the process or product. The expected results include detailed logs of how developers construct software during XP 2016, their preferences for software construction recommendations, and which effects accepted suggestions have on task execution and outcome

ADMA as a possible marker of endothelial damage. A study in young asymptomatic patients with cerebral small vessel disease.

Sporadic small vessel disease (SVD) has high prevalence in aging population and stroke patients, but also in younger asymptomatic subjects. In this last group it can represents a prelude to stroke and cognitive impairment. Still nowadays, its pathogenesis is unclear. 35 consecutive patients with SVD at brain MRI and 35 age- and sex-matched controls, between January 2016 and February 2018, underwent an extended screening for thrombophilia, autoimmunity and evaluated levels of blood markers of inflammation and endothelial activation. Asymmetric DiMethyl Arginine (ADMA) levels proved higher in patients (70.44 \ub1 36.25 ng/ml vs. 46.58 \ub1 30.67 ng/ml; p = 0.004), also after controlling for confounding factors. ADMA levels showed positive correlation with Fazekas score (r = 0.304; p = 0.01). ROC curve analysis showed a moderate accuracy in discriminating patients and controls (AUC\u2009= 0.70; CI 0.57\u20130.82; p = 0.004): a cut-off of 46 ng/ml is associated with 80% sensitivity, but limited (54%) specificity. Higher ADMA levels characterize selected subjects with sporadic SVD, asymptomatic for vascular diseases and without latent inflammatory conditions or coagulopathy. This reinforces the hypothesis of the key role of endothelial dysfunction in SVD. Further studies should explore the cause-effect relationship between ADMA pathway and SVD

Critically appraised topic on Rapid Eye Movement Behavior Disorder: From protein misfolding processes to clinical pathophysiology and conversion to neurodegenerative disorders

Background: REM Behavior Disorder (RBD) is considered one of most powerful prodromal condition in different neurodegenerative disorders, mainly alpha-synucleinopathies. A large amount of research recently explored this relationship. Objective and Design: The present critically appraised review undertakes this topic, from the perspective of the pathogenetic interplay between clinical manifestations in RBD patients and the misfolding processes that characterize neurodegeneration. In particular, evidence in favor and against the role of RBD as a biomarker of neurodegeneration is discussed. Results and Conclusion: The selected papers were functional to structure the review into three main sections: 1) Protein misfolding in neurodegenerative disorders with focus on alpha-synuclein; 2) Clinical features, diagnosis, and pathophysiology of RBD; 3) RBD as a clinical biomarker of protein misfolding. Data herein highlights the current knowledge and the areas of uncertainties in the relationship between RBD and neurodegenerative disorders; we went through preclinical, prodromal and clinical stages of neurodegenerative processes as a useful reference for clinicians involved in brain pathological aging and future research in this field

The use of alteplase, although safe, does not offer clear clinical advantages when mild stroke is non-disabling

IntroductionIt is unknown whether alteplase is effective and safe in patients with mild acute ischemic stroke (AIS). Determining whether symptoms are “disabling” or not is a crucial factor in the management of these patients. This study aimed to investigate the efficacy and safety of alteplase in patients with mild, non-disabling AIS.MethodsWe included all consecutive patients admitted for AIS at our institution from January 2015 to May 2022 who presented a baseline NIHSS score of 0–5 and fit the criteria to receive intravenous thrombolysis. In order to select only subjects with non-disabling AIS, we excluded patients who scored more than 1 point in the following NIHSS single items: vision, language, neglect, and single limb. Patients who scored at least 1 point in the NIHSS consciousness item were excluded as well. This study is a retrospective analysis of a prospectively collected database.ResultsAfter the application of the exclusion criteria, we included 319 patients, stratified into patients receiving and not receiving alteplase based on non-disabling symptoms. The two groups were comparable regarding demographic and clinical data. Rates of a 3-month favorable outcome, defined as a 3-month mRS score of 0–1, were similar, being 82.3% and 86.1% in the treated and untreated patients, respectively. Hemorrhagic complications and mortality occurred infrequently and were not affected by alteplase treatment.DiscussionThis observational study suggests that the use of alteplase, although safe, is not associated with a better outcome in highly selected patients with non-disabling AIS

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19

Purpose: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. Methods: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19\u2009+) versus controls without COVID-19 (COV19\u2009-). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. Results: A total of 33 COV19\u2009+\u2009patients and 321 COV19\u2009-\u2009controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19\u2009+\u2009population. uHG was significantly higher among COV19\u2009+\u2009patients (median 6.2 mL/h vs 3.1 mL/h, p\u2009=\u20090.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE)\u2009=\u20090.31 (0.11), p\u2009=\u20090.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE)\u2009=\u20090.29 (0.13), p\u2009=\u20090.026). Conclusions: ICH in COV19\u2009+\u2009patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

IMPORTANCE: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. OBJECTIVE: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. EXPOSURES: Type of acute symptomatic seizure. MAIN OUTCOMES AND MEASURES: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). RESULTS: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. CONCLUSIONS AND RELEVANCE: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up

Genome-wide association study of REM sleep behavior disorder identifies polygenic risk and brain expression effects

Rapid-eye movement (REM) sleep behavior disorder (RBD), enactment of dreams during REM sleep, is an early clinical symptom of alpha-synucleinopathies and defines a more severe subtype. The genetic background of RBD and its underlying mechanisms are not well understood. Here, we perform a genome-wide association study of RBD, identifying five RBD risk loci near SNCA, GBA, TMEM175, INPP5F, and SCARB2. Expression analyses highlight SNCA-AS1 and potentially SCARB2 differential expression in different brain regions in RBD, with SNCA-AS1 further supported by colocalization analyses. Polygenic risk score, pathway analysis, and genetic correlations provide further insights into RBD genetics, highlighting RBD as a unique alpha-synucleinopathy subpopulation that will allow future early intervention