Background
Patent foramen ovale (PFO) closure is superior to medical therapy alone to prevent stroke recurrence in selected patients. Small cortical infarcts and large right to left shunts seem to ...identify patients who will benefit most from closure. We aimed to study the correlation between the size of the PFO and the volume of cerebral ischemic lesions in young patients with cryptogenic ischemic stroke.
Methods
PFO dimensions and acute ischemic lesion volume of 20 patients, aged<55 years, were analyzed with transesophageal echocardiography and brain magnetic resonance imaging, respectively. The association between the volume of ischemic lesions with the length of PFO, maximum separation between septum primum and septum secundum, and the combination of the twos was explored.
Results
A direct statistically significant correlation was found between cerebral lesion volume and maximum separation of septum primum and septum secundum (p=0.047). Length of PFO showed a non-significant trend towards an inverse correlation with lesion volume (p=0.603). Multiple linear regression analysis showed that cerebral lesion volume was dependent directly on maximum separation and inversely on length of PFO (regression coeff. −0,837; p= 0.057; 2,536, p=0.006, respectively).
Conclusions
These data suggest that even small PFO might be pathogenetic in case of small cerebral infarcts and that large cerebral infarcts might be PFO related if the shunt is large. If confirmed, the combination of detailed characteristics of PFO with the volume of cerebral infarct could be integrated in a new score to select patients who would take real advantage from a percutaneous closure.
Oral migalastat has recently been approved for the treatment of Anderson-Fabry disease (FD) in patients aged ≥16 years with amenable mutations on the basis of two phase III trials, FACETS and ...ATTRACT. However, with the introduction of migalastat into clinical practice, it is important to correctly identify the patients who may gain the most benefits from this therapy. Due to the relatively recent availability of migalastat, its role in clinical practice still has to be included in guidelines or recommendations. On these bases, a multidisciplinary group of Italian Experts in the treatment of FD has run the GALA project, with the aim to collect the opinions of expert physicians and to propose some starting points for an experience-based use of migalastat.
Overall, although studies and data from longer-term follow-up with migalastat are still emerging, available evidence is consistent in showing that this molecule does represent a suitable therapy for the treatment of FD, in patients aged ≥16 years and with amenable mutations. The use of migalastat as an oral option appears to be overall safe, and experience thus far indicates potential for improving quality of life, controlling GI symptoms, stabilizing renal function and reducing cardiac hypertrophy.
Migalastat can be considered either as a first-line therapy - given its efficacy, extensive tissue penetration, convenient oral regimen, and the current limited therapeutic options available - or in patients on enzyme-replacement therapy (ERT) who experience side effects, with poor compliance to chronic i.v. therapy, or with clinical evidence of progression of the disease.
Acute ischemic stroke with isolated occlusion of the M2-segment middle cerebral artery (MCA) has not been a focus of trials on mechanical thrombectomy (MT) thus far. We aimed to assess outcomes in ...stroke patients treated with different endovascular procedures versus direct MT alone for isolated M2-MCA occlusion. We conducted a cohort study on data from 506 stroke patients with isolated M2-MCA occlusion who were enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort. We calculated odds ratio (OR) with confidence interval (CI) of different endovascular procedures (vs direct MT alone) for outcomes after adjustment for age, enrollment period, pre-stroke mRS score, NIHSS score, ASPECT score, onset-to-groin time, and procedure time. Endovascular procedures were direct MT alone (n = 156), intravenous thrombolysis (IVT) plus MT (n = 266), MT plus intra-arterial thrombolysis (IAT) (n = 43), and IAT alone (n = 41). MT plus IAT was associated with higher rates of TICI 2b/3 (OR 3.281, 95% CI 1.006–10.704), 3-month mRS 0–1 (OR 4.153, 95% CI 1.267–13.612), and 3-month mRS 0–2 (OR 4.497, 95% CI 1.485–13.617). IAT alone was associated with lower rates of TICI 3 (OR 0.348, 95% CI 0.139–0.874) and TICI 2b/3 (OR 0.369, 95% CI 0.144–0.948). IVT plus MT was associated with higher rate of asymptomatic ICH (OR 2.526, 95% CI 1.145–5.571). No significant difference was found between different endovascular procedures and direct MT alone as regards symptomatic ICH and 3-month death. In stroke patients with isolated M2-MCA occlusion, MT plus IAT was associated with better outcomes as compared with direct MT alone.
Cerebral edema (CE) and hemorrhagic transformation (HT) are frequent and unpredictable events in patients with acute ischemic stroke (AIS), even when an effective vessel recanalization has been ...achieved. These complications, related to blood-brain barrier (BBB) disruption, remain difficult to prevent or treat and may offset the beneficial effect of recanalization, and lead to poor outcomes. The aim of this translational study is to evaluate the association of circulating and imaging biomarkers with subsequent CE and HT in stroke patients with the dual purpose of investigating possible predictors as well as molecular dynamics underpinning those events and functional outcomes. Concurrently, the preclinical study will develop a new mouse model of middle cerebral artery (MCA) occlusion and recanalization to explore BBB alterations and their potentially harmful effects on tissue. The clinical section of the study is based on a single-center observational design enrolling consecutive patients with AIS in the anterior circulation territory, treated with recanalization therapies from October 1, 2015 to May 31, 2020. The study will employ an innovative evaluation of routine CT scans: in fact, we will assess and quantify the presence of CE and HT after stroke in CT scans at 24 h, through the quantification of anatomical distortion (AD), a measure of CE and HT. We will investigate the relationship of AD and several blood biomarkers of inflammation and extracellular matrix, with functional outcomes at 3 months. In parallel, we will employ a newly developed mouse model of stroke and recanalization, to investigate the emergence of BBB changes 24 h after the stroke onset. The close interaction between clinical and preclinical research can enhance our understanding of findings from each branch of research, enabling a deeper interpretation of the underlying mechanisms of reperfusion injury following recanalization treatment for AIS.
Background
TIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician’s attention. No definite ...indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry’s stroke are scanty.
Methods
The study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event.
Discussion
The potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke.
The approach to reperfusion therapies in stroke patients is rapidly evolving, but there is still no explanation why a substantial proportion of patients have a poor clinical prognosis despite ...successful flow restoration. This issue of futile recanalization is explained here by three clinical cases, which, despite complete recanalization, have very different outcomes. Preclinical research is particularly suited to characterize the highly dynamic changes in acute ischemic stroke and identify potential treatment targets useful for clinical translation. This review surveys the efforts taken so far to achieve mouse models capable of investigating the neurovascular underpinnings of futile recanalization. We highlight the translational potential of targeting tissue reperfusion in fully recanalized mouse models and of investigating the underlying pathophysiological mechanisms from subcellular to tissue scale. We suggest that stroke preclinical research should increasingly drive forward a continuous and circular dialogue with clinical research. When the preclinical and the clinical stroke research are consistent, translational success will follow.
Introduction:
Patients with atrial fibrillation (AF) can experience ischemic stroke despite adequate anticoagulant therapy. The secondary prevention strategy of these so-called “resistant strokes” is ...empirical. Since about 90% of patients with ischemic stroke due to atrial fibrillation have thrombus in left atrial appendage (LAA) we sought to explore the possibility that resistant stroke could have a LAA morphology resistant to anticoagulants.
Case Report:
A 77 years old man affected by AF experienced two cardioembolic ischemic stroke while on anticoagulants. The study of LAA showed a windsock-like morphology in the proximal part while distally the LAA presented a cauliflower morphology with a large amount of pectinate muscles and blood stagnation. The precise characteristics of LAA were properly understood integrating images obtained by cardiac CT, transesophageal echocardiography, and selective angiography. A high risky LAA for thrombus formation was diagnosed and its occlusion (LAAO) as an add-on therapy to anticoagulants was proposed and performed. Six month follow-up was uneventfully.
Conclusion:
The systematic study of LAA in patients with resistant-stroke could help to identify LAA malignant morphology. The efficacy on stroke recurrence of the combined therapy (anticoagulants plus LAAO) is worthy to be tested in randomized trials.
Background Patients with an acute ischemic stroke rated as mild, and for this reason not submitted to thrombolysis, have an unfavorable outcome in a non-negligible proportion. Whether selective ...presentation features help identify those at risk of bad outcome, and whether it could be recommended to treat only patients with such features, is poorly elucidated. We report our experience based on retrospective evaluation of a consecutive series of patients scoring 6 or less on baseline National Institutes of Health Stroke Scale (NIHSS), some of whom received thrombolysis. Methods From the prospective Careggi Hospital Stroke Registry, Florence, Italy, we selected a series of patients who fulfilled the following criteria: (1) screening for treatment within 3 hours of symptom onset; (2) mild symptoms, defined as a score of 6 or less on NIHSS, with or without rapid improvement; (3) no other reason for exclusion from thrombolysis; (4) no previous disability; and (5) admission to the stroke unit. We choose a modified Rankin scale score of less than 2 to define a good 3-month functional outcome. We studied as potential outcome predictors: age, baseline NIHSS score, isolated aphasia, motor impairment with or without aphasia, thrombolysis, previous stroke or transient ischemic attack, and interactions between each of these factors and thrombolysis. Results Between February 2004 and June 2011, 128 patients fulfilled the selection criteria: 47 (36.7%) received tissue plasminogen activator, 81 (63.3%) did not. At 3 months, of the 81 patients not receiving tissue plasminogen activator, 14 (17.3%) had an unfavorable outcome, compared with 6 (12.8%) among the 47 treated. Hemorrhagic complications or death occurred in neither group. Adjusting for major confounders and for thrombolysis, the presence of aphasia on early assessment proved the only independent predictor of worse outcome. NIHSS score variation showed no effect. Conclusions Aphasia is an early marker of unfavorable outcome in mild ischemic stroke patients. In these patients thrombolysis should be considered beyond the NIHSS scoring.
Background Acute stroke patients with comorbid cancer (CC) are more preferably addressed with endovascular treatment (EVT) than thrombolytic therapy, due to the presumed potential risk of hemorrhagic ...transformation and systemic bleeding. This study aims to evaluate clinical and procedural outcomes of acute stroke patients with CC receiving EVT. Methods Using the Italian Registry of Endovascular Treatment in Acute Stroke, we reviewed prospectively collected data of CC patients treated with EVT from 2011 to 2017. Outcome measures were modified Thrombolysis in Cerebral Infarction score, symptomatic intracranial hemorrhage rate, and 3‐month modified Rankin scale. We also compared CC patients with a control group without cancer (non‐comorbid cancer) receiving EVT and matched the 2 populations with a 1:1 propensity score. Results Out of 4598 stroke patients treated with EVT, 165 (3.6%) had a CC. Modified Thrombolysis in Cerebral Infarction 2b‐3 was obtained in 73.8% of CC and 74.5% of non‐comorbid cancer patients ( P =0.84), whereas the rate of symptomatic intracranial hemorrhage rate was 8.2% and 6.9%, respectively. Three‐month all‐cause mortality was 33.3% in CC patients and 18.6% non‐comorbid cancer patients ( P <0.001), and after propensity score was 35.4% and 22.1%, respectively ( P =0.012). In CC patients, the presence of metastasis and a more recent diagnosis of cancer were significantly associated with a higher 3‐month mortality ( P =0.018 and 0.021, respectively). Breast cancer showed a significant correlation with mild or no disability (odds ratio, 3.32; CI, 1.28–8.67; P =0.014) and less death cases at 3‐months (odds ratio, 0.44; CI, 0.16–1.21; P =0.114) compared to the other most represented malignancies. Conclusion Although 3‐month all‐cause mortality was significantly higher in CC patients, successful recanalization and hemorrhagic transformation rate were comparable in both groups. In cancer patients, a metastatic and active disease seem to be associated with a poorer functional outcome, whereas a diagnosis of breast cancer appears to be more frequent in patients with a mild or no disability at long term.
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