Acute revascularization treatments for ischemic stroke in the Stroke Units of Triveneto, northeast Italy: time to treatment and functional outcomes.

It is not known whether the current territorial organization for acute revascularization treatments in ischemic stroke patients guarantees similar time to treatment and functional outcomes among different levels of institutional stroke care. We aimed to assess the impact of time to treatment on functional outcomes in ischemic stroke patients who received intravenous thrombolysis (IVT) alone, bridging (IVT plus thrombectomy), or primary thrombectomy in level 1 and level 2 Stroke Units (SUs) in Triveneto, a geographical macroarea in Northeast of Italy. We conducted an analysis of data prospectively collected from 512 consecutive ischemic stroke patients who received IVT and/or mechanical thrombectomy in 25 SUs from September 17th to December 9th 2018. The favorable outcome measures were mRS score 0-1 and 0-2 at 3 months. The unfavorable outcome measures were mRS score 3-5 and death at 3 months. We estimated separately the possible association of each variable for time to treatment (onset-to-door, door-to-needle, onset-to-needle, door-to-groin puncture, needle-to-groin puncture, and onset-to-groin puncture) with 3-month outcome measures by calculating the odds ratios (ORs) with two-sided 95% confidence intervals (CI) after adjustment for pre-defined variables and variables with a probability value ≤ 0.10 in the univariate analysis for each outcome measure. Distribution of acute revascularization treatments was different between level 1 and level 2 SUs (p < 0.001). Among 182 patients admitted to level 1 SUs (n = 16), treatments were IVT alone in 164 (90.1%), bridging in 12 (6.6%), and primary thrombectomy in 6 (3.3%) patients. Among 330 patients admitted to level 2 SUs (n = 9), treatments were IVT alone in 219 (66.4%), bridging in 74 (22.4%), and primary thrombectomy in 37 (11.2%) patients. Rates of excellent outcome (51.4% vs 45.9%), favorable outcome (60.1% vs 58.7%), unfavorable outcome (33.3% vs 33.8%), and death (9.8% vs 11.3%) at 3 months were similar between level 1 and 2 SUs. No significant association was found between time to IVT alone (onset-to-door, door-to-needle, and onset-to-needle) and functional outcomes. After adjustment, door-to-needle time ≤ 60 min (OR 4.005, 95% CI 1.232-13.016), shorter door-to-groin time (OR 0.991, 95% CI 0.983-0.999), shorter needle-to-groin time (OR 0.986, 95% CI 0.975-0.997), and shorter onset-to-groin time (OR 0.994, 95% CI 0.988-1.000) were associated with mRS 0-1. Shorter door-to-groin time (OR 0.991, 95% CI 0.984-0.998), door-to-groin time ≤ 90 min (OR 12.146, 95% CI 2.193-67.280), shorter needle-to-groin time (OR 0.983, 95% CI 0.972-0.995), and shorter onset-to-groin time (OR 0.993, 95% CI 0.987-0.999) were associated with mRS 0-2. Longer door-to-groin time (OR 1.007, 95% CI 1.001-1.014) and longer needle-to-groin time (OR 1.019, 95% CI 1.005-1.034) were associated with mRS 3-5, while door-to-groin time ≤ 90 min (OR 0.229, 95% CI 0.065-0.808) was inversely associated with mRS 3-5. Longer onset-to-needle time (OR 1.025, 95% CI 1.002-1.048) was associated with death. Times to treatment influenced the 3-month outcomes in patients treated with thrombectomy (bridging or primary). A revision of the current territorial organization for acute stroke treatments in Triveneto is needed to reduce transfer time and to increase the proportion of patients transferred from a level 1 SU to a level 2 SU to perform thrombectomy.

Intravenous thrombolysis for ischemic stroke in the Veneto region: the gap between eligibility and reality.

Intravenous thrombolysis (IVT) is the treatment of choice for most patients with acute ischemic stroke. According to the recently updated guidelines, IVT should be administered in absence of absolute exclusion criteria. We aimed to assess the proportion of ischemic strokes potentially eligible and actually treated with IVT, and to explore the reasons for not administering IVT. We prospectively collected and analyzed data from 1184 consecutive ischemic stroke patients admitted to the 22 Stroke Units (SUs) of the Veneto region from September 18th to December 10th 2017. Patients were treated with IVT according to the current Italian guidelines. For untreated patients, the reasons for not administering IVT were reported by each center in a predefined model including absolute and/or relative exclusion criteria and other possible reasons. Out of 841 (71%) patients who presented within 4.5 h of stroke onset, 704 (59%) had no other absolute exclusion criteria and were therefore potentially eligible for IVT according to the current guidelines. However, only 323 (27%) patients were eventually treated with IVT. Among 861 (73%) untreated patients, 480 had at least one absolute exclusion criterion, 283 only relative exclusion criteria, 56 only other reasons, and 42 a combination of relative exclusion criteria and other reasons. Our study showed that only 46% (323/704) of the potentially eligible patients were actually treated with IVT in the SUs of the Veneto region. All healthcare professionals involved in the acute stroke pathway should make an effort to bridge this gap between eligibility and reality.

Herpes zoster infection and statins: which implications in clinical practice?

Herpes zoster (HZ), which is caused by reactivation of latent varicella zoster virus (VZV), constitutes a major public health concern in both short- and long-term periods. Over the last years, several epidemiological studies have demonstrated that statin use is associated with increased risk of HZ at cerebral level. Because statins are among the most popular and best-selling drugs in western countries, this potential negative pleiotropic effect could have important implications in the daily clinical practice. In the present manuscript, we reviewed the available data on the statin use and the relative risk of HZ infection.

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.

Could advanced drug delivery systems be the future in cardiovascular revascularization medicine?

Acute myocardial infarction, stroke and pulmonary embolism required a prompt revascularization to restore the normal blood flow as soon as possible. Fibrinolytic treatment has gradually become both dated and underused in the treatment of acute myocardial infarction, after the wide diffusion of cathlab and percutaneous transluminal coronary angioplasty. Conversely, the use of systemic thrombolysis remained a benchmark in the treatment of both ischemic stroke and massive pulmonary embolism. In daily clinical practice, the use of thrombolytic agents is often limited by absolute and/or relative contraindications and possible adverse events after the drug administration, as intracranial and/or extracranial bleeding events. To minimize these problems, during the last years, the introduction of nanotechnology in the field of cardiovascular revascularization medicine has created several fascinating results. In the present article, we describe these recent findings and their possible implications in future clinical practice.

Review of West Nile virus epidemiology in Italy and report of a case of West Nile virus encephalitis.

West Nile virus (WNV) is a flavivirus that causes neurological disorders in less than 1 % of infected subjects. Human cases of WNV-associated fever and/or neurological disorders have been reported in Italy since 2008. The first outbreak occurred in the northeastern region of Italy surrounding the Po River and was caused by the Po River lineage 1 strain, and since then, WNV infections have been reported in several regions of central Italy. Although the virus is highly genetically conserved, stochastic mutations in its genome may lead to the emergence of new strains, as was observed in Italy in 2011 with the identification of two new lineage 1 strains, the WNV Piave and WNV Livenza strains. To help further define WNV epidemiology in Italy, we describe a case of an Italian man living in the Po River area who developed fatal encephalitis in 2009 due to infection with the WNV Piave strain. This finding supports the notion that the Piave strain has been circulating in this area of Italy for 2 years longer than was previously believed.

18F-FDG PET/CT in tumefactive multiple sclerosis.

A 35-year-old man underwent contrast-enhanced MRI and F-FDG PET/CT for acute peripheral paresthesia, vision loss, muscle weakness, and difficulty walking. T2-weighted MRI demonstrated multiple bright periventricular supratentorial and infratentorial white matter lesions, including 2 with nodularity. Both nodular lesions showed moderate focal FDG uptake (SUVmax, 6.9 in both cases). Cerebrospinal fluid analysis showed increased levels of immunocytes and oligoclonal antibody bands. A diagnosis of acute onset tumefactive multiple sclerosis was made.

Improving migraine by means of primary transcatheter patent foramen ovale closure: long-term follow-up.

OBJECTIVE: We sought to assess the long-term faith of migraine in patients with high risk anatomic and functional characteristics predisposing to paradoxical embolism submitted to patent foramen ovale (PFO) transcatheter closure. METHODS: In a prospective single-center non randomized registry from January 2004 to January 2010 we enrolled 80 patients (58 female, mean age 42±2.7 years, 63 patients with aura) submitted to transcatheter PFO closure in our center. All patients fulfilled the following criteria: basal shunt and shower/curtain shunt pattern on transcranial Doppler and echocardiography, presence of interatrial septal aneurysm (ISA) and Eustachian valve, 3-4 class MIDAS score, coagulation abnormalities, medication-refractory migraine with or without aura. Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine before and after mechanical closure. High risk features for paradoxical embolism included all of the following. RESULTS: Percutaneous closure was successful in all cases (occlusion rate 91.2%), using a specifically anatomically-driven tailored strategy, with no peri-procedural or in-hospital complications; 70/80 of patients (87.5%) reported improved migraine symptomatology (mean MIDAS score decreased 33.4±6.7 to 10.6±9.8, p<0.03) whereas 12.5% reported no amelioration: none of the patients reported worsening of the previous migraine symptoms. Auras were definitively cured in 61/63 patients with migraine with aura (96.8%). CONCLUSIONS: Transcatheter PFO closure in a selected population of patients with severe migraine at high risk of paradoxical embolism resulted in a significant reduction in migraine over a long-term follow-up.

Intermittent Broca's aphasia management in an emergency unit: from theory to practice.

Although Broca's aphasia (BA) may mimic different neurological illness, its sudden onset often requires an emergency approach. In this paper, the management of a case of intermittent BA occurred in a young woman without history of neurological, cardiovascular and arrhythmic diseases is discussed. Diffusion-weighted magnetic resonance imaging showed two areas of hypoperfusion in the terminal branches of the left medial cerebral artery not previously diagnosed by computed tomography. Although there were no eligibility criteria for thrombolysis, patient received intravenous treatment with recombinant tissue-type plasminogen activator (rt-PA) over 1 h and at the end of rt-PA infusion aphasia completely disappeared without neurological sequelae. Transesophageal echocardiography revealed a thrombus in the left atrial appendage not previously detected by transthoracic echocardiography. In the month following the cardioembolic stroke, heart rhythm was monitored for 30 days by an external loop recorder and during this test two episodes of silent lone atrial fibrillation were collected.

Could genetic analysis be useful in reducing cerebrovascular risk in hypertensive subjects with hyperhomocysteinemia and patent foramen ovale? A 2-year follow-up study.

OBJECTIVES: Potential causes of cryptogenic cerebrovascular (CV) events are patent foramen ovale (PFO) and hyper homocysteinemia (H-Hcys), this latter a well-established risk factor for thrombosis particularly in the presence of mutation for the methylenetetrahydrofolate reductase (MTHFR) gene. This study investigated if in uncomplicated hypertensive subjects (HTs) with isolated PFO and H-Hcys, a different MTHFR polymorphism pattern for C667→T gene mutation could influence PFO management and to reduce the CV risk. METHODS: In thirty-two HTs aged 55.6±14.4years, PFO was diagnosed by echocardiography. MTHFR genotype was evaluated by a multiplex polymerase chain reaction with reverse line blot hybridization assay. In relation to the T allele distribution, HTs were divided in normal (CC), heterozygote (CT) and homozygote (TT) for the MTHFR genotype. All subjects received a supplementation of oral folate (5mg daily) and were evaluated yearly for 2years. Analysis of variance for repeated measures (ANOVA) was used to compare changes of Hcys at baseline and at the end of follow-up and differences between continuous variables were evaluated in the three MTHFR groups with the Tukey's post hoc test after adjustment for confounders. RESULTS: At the follow-up, Hcys levels significantly normalized from baseline both in TT (38.1±6.7 vs. 15±3.6, p<0.01) and CT (26.6±2.3 vs. 9.2±1.6, p<0.01) but not in CC subjects (18.2±1.8 vs. 16.0±1.6, NS). Independently of age, BMI, vitamin treatment both systolic and diastolic blood pressure (BP) significantly decrease at the follow-up in all the MTHFR genotypes. No CV events were observed during the follow-up. CONCLUSIONS: In HTs with isolated PFO and H-Hcys, oral folate supplementation reduces Hcys levels both in TT and CT subjects with C667→T mutation of MTHFR. In addition the BP normalization probably contributed to reduce CV risk in these genotypes.

SERCA1 and calsequestrin storage myopathy: a new surplus protein myopathy.

We describe four patients, from four different families, affected by a mild myopathy or asymptomatic elevated serum creatine kinase levels, in whom toluidine blue-stained semithin sections of muscle specimens revealed inclusions of different size and shape. The inclusions did not stain by routine histochemical studies. The sarcoplasmic or endoplasmic reticulum calcium 1 (SERCA1) ATPase and/or calsequestrin reactivity of inclusions, by immunohistochemistry, and the SERCA1- and calsequestrin-increased expression, by immunoblot, suggested that inclusions were constituted by an excess of proteins normally present in the terminal cisternae of sarcoplasmic reticulum. Our cases, both sporadic and familial, represent a new type of surplus protein myopathy.