Stress hyperglycemia is associated with futile recanalization in patients with anterior large vessel occlusion undergoing mechanical thrombectomy.

INTRODUCTION: Mechanical thrombectomy (MT) is the standard treatment for acute ischemic stroke (AIS) due to anterior large vessel occlusion (LVO). Despite successful recanalization, some patients remain disabled after 3 months. Mechanisms that can cause futile recanalization (FR) are still largely unknown. We investigated if stress hyperglycemia might be associated with FR. PATIENTS AND METHODS: This is a retrospective analysis of consecutive patients with successful recanalization treated in four participating centers between January 2021 and December 2022. According to the modified Rankin scale (mRS) status at 3 months, patients were divided into two groups: FR, if mRS score >2, and useful recanalization (UR), if mRS score ⩽2. Stress hyperglycemia was estimated by the glucose-to-glycated hemoglobin ratio (GAR) index. RESULTS: A total of 691 subjects were included. At 3 months, 403 patients (58.3%) were included in the FR group, while the remaining 288 patients (41.7%) were included in the UR group. At the multivariate analysis, variables independently associated with FR were the following: age (OR 1.04, 95% CI 1.02-1.06, p < 0.001), GAR index (OR 1.08, 95% CI 1.03-1.14, p = 0.003), NIHSS at admission (OR 1.16, 95% CI 1.11-1.22; p < 0.001), and procedure length (OR 1.01, 95% CI 1.00-1.02; p = 0.009). We observed that the model combining age, GAR index, NIHSS at admission, and procedure length had good predictive accuracy (AUC 0.78, 95% CI 0.74-0.81). CONCLUSIONS: Stress hyperglycemia predicts FR in patients with successful recanalization after MT. Further studies should explore if managing stress hyperglycemia may reduce futile recanalization. Additionally, we recommend paying close attention to AIS patients with a GAR index greater than 24.8 who exhibit a high risk of FR.

Isolated insular stroke: topography is the answer with respect to outcome and cardiac involvement.

Background and purpose: Isolated insular strokes (IIS) are a rare occurrence due to the frequent concomitant involvement of adjacent territories, supplied by the M2 segment of the middle cerebral artery (MCA), and clinical aspects are sometimes contradictory. We aimed to describe clinical and radiological characteristics of a pure IIS case series, focusing on its functional outcome and cardiac involvement. Methods: We identified 15 isolated insular ischemic strokes from a pool of 563 ischemic strokes occurred between January 2020 and December 2021. Data collection consisted of demographic and baseline clinical characteristics, comorbidities, electrocardiograms, echocardiograms, stroke topography and etiology, reperfusive treatments, and outcome measures. Descriptive statistical analysis was carried out. Results: Newly detected cardiovascular alterations were the prevalent atypical presentation. Cardioembolism was the most frequent etiology. Most of patients had major neurological improvement at discharge and good outcome at 3-months follow-up. Discussion and conclusion: IIS are extremely rare, representing according to our study about 2.6% ischemic strokes cases per year, and patients have peculiar clinical manifestations, such as dysautonomia and awareness deficits. Our data suggest the possibility for these patients to completely recover after acute ischemic stroke notwithstanding the pivotal role of the insula in cerebral connections and the frequent association with MCA occlusion. Moreover, given the central role of the insula in regulating autonomic functions, newly detected cardiac arrhythmias must be taken into consideration, as well as a full diagnostic work-up for the research of cardioembolic sources. To our knowledge, this is the largest monocentric case series of IIS and it might be useful for future systematic reviews.

Comparison of pharmacokinetic properties of alteplase and tenecteplase. The future of thrombolysis in acute ischemic stroke.

INTRODUCTION: The drug most frequently used for thrombolysis in cases of acute ischemic stroke (AIS) is alteplase. However, there is moderate-to-high-quality evidence that tenecteplase has similar or higher efficacy and safety. With improved pharmacokinetic properties over alteplase, tenecteplase could be a significant advantage in treating AIS. AREAS COVERED: After conducting an extensive search on Scopus and PubMed, this manuscript reviews and compares the pharmacokinetic properties of alteplase and tenecteplase. Additionally, it provides information on pharmacodynamics, clinical efficacy, safety, tolerability, and drug-drug interactions. EXPERT OPINION: The pharmacokinetic profile of alteplase and tenecteplase is derived from studies in patients with acute myocardial infarction. Thanks to its pharmacokinetic properties, tenecteplase is the drug closest to being the ideal fibrinolytic for AIS. Its longer half-life enables a single-bolus administration, which is particularly useful in emergencies. Tenecteplase has proven to have a good efficacy and safety profile in randomized clinical trials. Although we are awaiting the results of the ongoing phase 3 randomized clinical trials, we believe that tenecteplase has the potential to revolutionize the treatment of AIS through thrombolysis.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Electrocardiographic RR Interval Dynamic Analysis to Identify Acute Stroke Patients at High Risk for Atrial Fibrillation Episodes During Stroke Unit Admission.

Patients at short-term risk of paroxysmal atrial fibrillation (PAF) often exhibit increased RR interval variability during sinus rhythm. We studied if RR dynamic analysis, applied in the first hours after stroke unit (SU) admission, identified acute ischemic stroke patients at higher risk for subsequent PAF episodes detected within the SU hospitalization. Acute ischemic stroke patients underwent continuous cardiac monitoring (CCM) using standard bedside monitors immediately after SU admission. The CCM tracks from the first 48 h were analyzed using a telemedicine service (SRA clinic, Apoplex Medical, Germany). Based on the RR dynamics, the stroke risk analysis (SRA) algorithm stratified the risk for PAF as follows: low risk for PAF, high risk for PAF, presence of manifest AF. The subsequent presence/absence of PAF during the whole SU hospitalization was ruled out using all available CCMs, standard ECGs, or 24-h Holter ECGs. Two hundred patients (40% females, mean age 71 ± 16 years) were included. According to the initial SRA analysis, 111 patients (56%) were considered as low risk for PAF, 52 (26%) as high risk while 37 patients (18%) had manifest AF. A low-risk level SRA was associated with a reduced probability for subsequent PAF detection (1/111, 0.9%, 95% CI 0-4.3%) while a high-risk level SRA predicted an increased probability (20/52, 38.5% (95% CI 25-52%). RR dynamic analysis performed in the first hours after ischemic stroke may stratify patients into categories at low or high risk for forthcoming paroxysmal AF episodes detected within the SU hospitalization.

Introduction of direct oral anticoagulant within 7 days of stroke onset: a nomogram to predict the probability of 3-month modified Rankin Scale score > 2.

In clinical practice, direct oral anticoagulants (DOACs) are often started earlier (≤ 7 days) than in randomized clinical trials after stroke. We aimed to develop a nomogram model incorporating time of DOAC introduction ≤ 7 days of stroke onset in combination with different degrees of stroke radiological/neurological severity at the time of treatment to predict the probability of unfavorable outcome. We conducted a multicenter prospective study including 344 patients who started DOAC 1-7 days after atrial fibrillation-related stroke onset. Computed tomography scan 24-36 h after stroke onset was performed in all patients before starting DOAC. Unfavorable outcome was defined as modified Rankin Scale (mRS) score > 2 at 3 months. Based on multivariate logistic model, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve (AUC-ROC) and calibration of risk prediction model by using the Hosmer-Lemeshow test. Onset-to-treatment time for DOAC (OR: 1.21, p = 0.030), NIH Stroke Scale (NIHSS) score at the time of treatment (OR: 1.00 for NIHSS = 0-5; OR: 2.67, p = 0.016 for NIHSS = 6-9; OR: 26.70, p < 0.001 for NIHSS = 10-14; OR: 57.48, p < 0.001 for NIHSS ≥ 15), size infarct (OR: 1.00 for small infarct; OR: 2.26, p = 0.023 for medium infarct; OR: 3.40, p = 0.005 for large infarct), and age ≥ 80 years (OR: 1.96, p = 0.028) remained independent predictors of unfavorable outcome to compose the nomogram. The AUC-ROC of nomogram was 0.858. Calibration was good (p = 2.889 for the Hosmer-Lemeshow test). The combination of onset-to-treatment time of DOAC with stroke radiological/neurological severity at the time of treatment and old age may predict the probability of unfavorable outcome.

Prevalence of Restless Legs Syndrome in Migraine Patients: A Case-Control Study. Analysis of Risk Factors for Restless Legs Syndrome in Migraine Patients.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor disorder. It can be idiopathic, associated to other diseases or to pharmacologic treatments. RLS has been reported to occur more frequently in migraine patients, but a clear pathogenetic link seems still under debate. We aimed to evaluate RLS prevalence in migraine, impact on sleep quality and the main clinical determinants of this association. METHODS: Migraine patients and age- and sex-matched controls were enrolled from 1st January 2011 to 30th December 2012. Migraine and RLS diagnosis complied with already published clinical criteria. Medical and pharmacological histories, as well as structured questionnaires were collected. RESULTS: RLS was found in 29/180 (16.1%) patients and 11/180 (6.1%) controls. The odds ratio (OR) for RLS was 2.95 (CI 95%, 1.42-6.11). Among migraine patients, after adjustment for possible confounding factors, familial history (OR 3.863, CI 1.076-13.873), and serotoninergic overload (OR 3.654, CI 1.347-9.916) were significantly associated with RLS occurrence. Pittsburgh Sleep Quality Index score was higher in migraine patients with RLS than in subjects without RLS. CONCLUSIONS: The confirmed association between migraine and RLS might be because of familial predisposition and to serotoninergic drugs effect, possibly interfering with the balance between dopaminergic and serotoninergic pathways.

Inhibidores de la angiogénesis (bevacizumab - ranibizumab) en glaucoma neovascular y neovascularización corneal / Angiogenesis inhibitors (bevacizumab - ranibizumab) in neovascular glaucoma and corneal neovascularization

CONTEXTO CLÍNICO: Se denomina glaucoma a un grupo de enfermedades oculares caracterizadas habitualmente por un daño en el nervio óptico, frecuentemente asociado a una presión intraocular (PIO) elevada. Constituye la segunda causa de ceguera en el mundo luego de las cataratas. Existen formas primarias idiopáticas y formas secundarias que pueden deberse a uveítis, trauma, terapia con glucocorticoides, o retinopatías vasoproliferativas. El glaucoma de ángulo abierto, se caracteriza por una pérdida progresiva del campo visual. Su prevalencia es inferior al 1% en los individuos menores de 55 años de edad y alcanza el 4% a los 80 años de edad. El diagnóstico se realiza habitualmente mediante la visualización del nervio óptico con el fondo de ojo para evaluar la neuropatía. También se recurre a estúdios funcionales como el campo visual computarizado. El glaucoma de ángulo estrecho ocurre en pacientes con cierta predisposición anatómica. Entre las causas secundarias se encuentran la proliferación vascular del iris, que puede observarse en retinopatías proliferativas como la retinopatía diabética, y que se denomina glaucoma neovascular (GNV). El tratamiento del glaucoma de ángulo abierto en primera instancia es de tipo farmacológico tópico, luego terapia fotodinámica (TFD) y por último cirugía, que puede consistir en uma técnica denominada trabeculectomía y tratamiento combinado con mitomicina c para evitar la cicatrización. TECNOLOGÍA: El bevacizumab es un anticuerpo monoclonal recombinante que bloquea la interacción entre el VEGF-A y sus receptores (VEGF-1 y VEGF-2), inhibiendo la formación de nuevos vasos sanguíneos. Para el tratamiento del GNV, el bevacizumab se administra en forma intravítrea, y para el tratamiento de la NVC se administra en forma tópica, subconjuntival, o intraocular. La dosis para tratamiento de glaucoma neovascular es 1,25 mg administrado por inyección intravítrea una vez al mes. Ranibizumab es el fragmento Fab del mismo anticuerpo utilizado para crear bevacizumab, pero se une al VEGF-A con afinidad significativamente mayor. Al igual que el bevacizumab, inhibe la formación de nuevos vasos sanguíneos. Los efectos secundarios más comunes son la hemorragia conjuntival, dolor ocular, flotadores vítreos, aumento de la PIO e inflamación intraocular. Se recomienda una dosis de 0,5 mg administrada en forma intravítrea, una vez al mes para el tratamiento del glaucoma neovascular. OBJETIVO: Evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura de Inhibidores de la angiogénesis (bevacizumab y ranibizumab) en GNV y la NVC. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas (incluyendo Medline, Cochrane y CRD), en buscadores genéricos de Internet, agencias de evaluación de tecnologias sanitarias y financiadores de salud utilizando las siguientes estrategias: (Glaucoma, Neovascular[Mesh] OR Glaucom*[tiab]) AND (Bevacizumab[Mesh] OR Bevacizumab[tiab] OR Avastin[tiab] OR Ranibizumab[Mesh] OR RhuFab[tiab] OR Ranibizumab[tiab] OR Lucentis[tiab]). (Corneal Neovascularization[Mesh] OR Corneal Neovasculari*[tiab] OR Corneal Angiogenesis[tiab]) AND (Bevacizumab[Mesh] OR Bevacizumab[tiab] OR Avastin[tiab] OR Ranibizumab[Mesh] OR RhuFab[tiab] OR Ranibizumab[tiab] OR Lucentis[tiab]). Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias y económicas, guías de práctica clínica y políticas de cobertura de otros sistemas de salud cuando estaban disponibles. RESULTADOS: En relación al tratamiento del glaucoma neovascular se incluyeron dos RS, un ensayo clínico no aleatorizado, una serie de casos, una evaluación de tecnología sanitaria y dos políticas de cobertura. En relación al tratamiento de la neovascularización corneal se incluyeron una RS, un ECA, uma guía de práctica clínica y dos políticas de cobertura. CONCLUSIONES: Evidencia de moderada calidad muestra que el bevacizumab comparado con placebo podría tener cierta efectividad para reducir la presión intraocular en pacientes con glaucoma neovascular, aunque los datos son inciertos. Al compararlo con mitomicina c como adyuvante de la cirugía de trabeculectomía, no se observaron diferencias significativas en cuanto a la disminución de la presión intraocular. Evidencia de baja calidad indica que el ranibizumab no produciría cambios significativos en la presión intraocular al aplicarlo en pacientes con glaucoma neovascular. Las guías de práctica clínica relevadas consideran al bevacizumab como una opción entre otras como la terapia fotodinámica o la cirugía. No se encontraron guías que recomienden el uso de ranibizumab. Los financiadores estadounidenses relevados brindan cobertura del bevacizumab a pacientes con glaucoma neovascular. Sólo una de ellas brinda cobertura de ranibizumab para esta indicación. En cuanto al tratamiento de la neovascularización corneal, evidencia de muy baja calidad muestra que el bevacizumab podría reducir el área de neovascularización, aunque no necesariamente esto se traduciría en beneficios clínicos concretos, y no demostró ser superior a otras alternativas terapéuticas como la terapia fotodinámica. No se encontraron estudios que comparasen ranibizumab con los tratamientos habituales. Por estos motivos las guías de práctica clínica no suelen considerarlo como una alternativa y los financiadores de salud estadounidenses relevados no prestan cobertura por considerar estos tratamientos como experimentales.

In vivo confocal microscopy study of ocular surface neoplasia manifesting after radial keratotomy and laser in situ keratomileusis.

We report a case of ocular surface neoplasia in a patient with history of radial keratotomy and laser in situ keratomileusis. In vivo confocal microscopy of the cornea was useful to evaluate whether the incisions and scars of previous refractive surgeries were involved and to establish appropriate therapy.