To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies.
A sample size of 80 patients ...(40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at
= 0.05, two sided.
TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm.
The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h.
RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue.
ClinicalTrials.gov, identifier: NCT04400981.
The optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to ...investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS.BACKGROUNDThe optimal treatment for acute minor ischemic stroke is still undefined. and options include dual antiplatelet treatment (DAPT), intravenous thrombolysis (IVT), or their combination. We aimed to investigate benefits and risks of combining IVT and DAPT versus DAPT alone in patients with MIS.This is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale mRS score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% 95% CI -2.0% to 6.7%; P=0.295; risk ratio, 1.03 95% CI 0.98-1.08; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 95% CI 0.41-0.79; P<0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% 95% CI 13.1%-28.6%; risk ratio, 1.59 95% CI 1.34-1.89; both P<0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 95% CI 0.08-0.90; P=0.034). There were no differences in safety outcomes.METHODS AND RESULTSThis is a prespecified propensity score-matched analysis from a prospective multicentric real-world study (READAPT Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack). We included patients with MIS (National Institutes of Health Stroke Scale score at admission ≤5), without prestroke disability (modified Rankin scale mRS score ≤2). The primary outcomes were 90-day mRS score of 0 to 2 and ordinal mRS distribution. The secondary outcomes included 90-day risk of stroke and other vascular events and 24-hour early neurological improvement or deterioration (≥2-point National Institutes of Health Stroke Scale score decrease or increase from the baseline, respectively). From 1373 patients with MIS, 240 patients treated with IVT plus DAPT were matched with 427 patients treated with DAPT alone. At 90 days, IVT plus DAPT versus DAPT alone showed similar frequency of mRS 0 to 2 (risk difference, 2.3% 95% CI -2.0% to 6.7%; P=0.295; risk ratio, 1.03 95% CI 0.98-1.08; P=0.312) but more favorable ordinal mRS scores distribution (odds ratio, 0.57 95% CI 0.41-0.79; P<0.001). Compared with patients treated with DAPT alone, those combining IVT and DAPT had higher 24-hour early neurological improvement (risk difference, 20.9% 95% CI 13.1%-28.6%; risk ratio, 1.59 95% CI 1.34-1.89; both P<0.001) and lower 90-day risk of stroke and other vascular events (hazard ratio, 0.27 95% CI 0.08-0.90; P=0.034). There were no differences in safety outcomes.According to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns.CONCLUSIONSAccording to findings from this observational study, patients with MIS may benefit in terms of better functional outcome and lower risk of recurrent events from combining IVT and DAPT versus DAPT alone without safety concerns.URL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT05476081.
Transesophageal echocardiography (TEE) has detected a high prevalence of patent foramen ovale (PFO) in stroke patients, but the clinical implications of the distinctive characteristics of this ...patency are still a matter of debate.
We studied 350 patients with acute ischemic stroke or transient ischemic attack (TIA) within 1 week of admission. Of these, 101 (29%) were identified by contrast TEE to have a PFO; 86 patients (25%) were cryptogenic stroke patients, and 163 were excluded because of the presence of a definite or possible arterial or clinical evidence of a source of emboli or small-vessel disease. Thirteen PFO subjects without a history of embolism were designated as the control group. All PFO and cryptogenic stroke patients were followed up by neurological visits.
Compared with controls, PFO patients with acute stroke or TIA more frequently presented with a right-to-left shunt at rest and a higher membrane mobility (P:<0. 05). Patients with these characteristics were considered to be at high risk. During a median follow-up period of 31 months (range, 4 to 58 months), 8 PFO and 18 cryptogenic stroke patients experienced recurrent cerebrovascular events. The cumulative estimate of risk of cerebrovascular event recurrence at 3 years was 4.3% (95% confidence interval CI, 0% to 10.2%) for "low-risk" PFO patients, 12.5% (95% CI, 0% to 26.1%) for "high-risk" PFO patients, and 16.3% (95% CI, 7. 2% to 25.4%) for cryptogenic stroke patients (high-risk PFO versus low-risk PFO, P:=0.05).
The association of right-to-left shunting at rest and high membrane mobility, as detected by contrast TEE, seems to identify PFO patients with cerebrovascular ischemic events who are at higher risk for recurrent brain embolism.
Background
Since its approval, the use of alteplase had been limited to patients aged ≤80 years.
Aims
TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with ...acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence.
Methods
TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0–2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly.
Results
Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69–2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights.
Conclusions
The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.
Background and purpose: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ...ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs. Methods: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD 2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment. Results: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding. Conclusions: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.
The role of genetic factors in the individual predisposition to develop ischemic stroke has been assessed by previous studies performed both in animal models and in humans. The main goal of the ...current investigation was to determine the possible contribution of genes encoding procoagulant and inflammatory factors on the occurrence of ischemic stroke in a cohort of young cases and corresponding controls. One hundred and fifteen cases of ischemic stroke were recruited for this study. A detailed clinical assessment, a definite etiologic diagnosis, as well as the presence/absence of known risk factors for ischemic stroke were obtained for each patient. As a control group 180 healthy, unrelated subjects were included. The whole population was screened for polymorphisms belonging to genes encoding FII, FV, α‐fibrinogen, β‐fibrinogen, GP IIb/IIIa, tumor necrosis factor (TNF)‐α, interleukin 1‐β. Hypertension was the most important risk factor for ischemic stroke in our cohort OR = 6.9, confidence interval (CI) 2.9–16.7, P < 0.0001. Among all genes tested, the TNF‐α gene variant exerted a significant, independent effect on individual predisposition to ischemic stroke occurrence (OR = 1.8, CI = 1.01–3.3, P < 0.05). Our findings, obtained in a cohort of young Italian patients, may support the existence of a direct contributory role of TNF‐α, a proinflammatory cytokine protein, in the susceptibility to brain damage.
Purpose
The aim of this study was to verify the sensitivity and specificity of the hyperdense middle cerebral artery sign (HMCAS) obtained by multidetector computed tomography (CT) in predicting ...acute stroke, using diffusion-weighted (DW) magnetic resonance imaging (MRI) as a reference. The location of the HMCAS, the extension of the ischaemic lesion and its prognostic value were also assessed.
Materials and methods
The CT examinations of 654 patients with symptoms related to acute cerebral stroke were retrospectively reviewed. DW-MRI confirmed recent stroke in 175 patients. Two expert neuroradiologists analysed the CT examinations of these patients in four phases. Sensitivity, specificity and interobserver reliability was evaluated. Patients were divided into three groups according to the HMCAS site (M1–M2–M3) and the Alberta Stroke Program Early CT Score (ASPECTS) on DW-MRI was calculated. The ASPECTS average score was correlated with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at 3 months.
Results
In 41 patients, the presence of HMCAS was confirmed (71 % sensitivity; 100 % specificity; Interobserver reliability
k
, 84 %). An inverse correlation was found by comparing the ASPECTS and NIHSS scores (Rsq = −0.206). After logistic regression analysis, HMCAS was found to be independently associated with a poor outcome (mRS >2) at 3 months after adjusting for age, NIHSS on admission, risk factors and aetiology of stroke.
Conclusions
Our study demonstrated that HMCAS obtained with multidetector CT can be detected in more than 70 % of patients with large acute ischaemic lesion and it is an unfavourable prognostic sign.
The identification of diffuse axonal injury (DAI) can be difficult, especially using conventional imaging (CT or MRI), which usually appears normal. Diffusion tensor imaging (DTI) is useful in ...identifying white matter abnormalities in patients with DAI. We describe the case of a 17-year-old female with severe closed head injury and right-side hemiparesis, studied with DTI and MR-tractography. In this case, DTI was useful to detect focal and diffuse signs of DAI.
Determinants of long-term outcome are not well defined in minor stroke patients. This study aims to evaluate which factors are independent long-term predictors of death and major stroke recurrence in ...a cohort of minor ischemic strokes.
A cohort of 322 patients with first-ever minor ischemic strokes (mean age, 55 years; 89% were treated with antiplatelet or anticoagulant drugs) with minor (Rankin score=2) or no disability (Rankin score <2) were followed for 10 years, with only 6% lost to follow-up. Death and major stroke recurrence rates were evaluated by Kaplan-Meier analysis. Hazard ratios and 95% confidence intervals (CI) of factors with P<.1 at the log-rank test were evaluated by multivariate Cox analysis.
The 10-year mortality rate was 32%, with a relative risk of 1.7 (95% CI, 1.4 to 2.1) compared with the age- and sex-matched general population. The 10-year recurrence rate of major strokes was 14%. The hazard ratio (95% CI) of death was 1.1 (1.05 to 1.09) for age (1-year increments), 3.4 (2.2 to 5.2) for minor disability, 1.8 (1.1 to 3.1) for myocardial infarction (MI), 2.0 (1.1 to 3.7) for nonvalvular atrial fibrillation, and 1.8 (1.2 to 2.7) for hypercholesterolemia. The hazard ratio (95% CI) of major stroke recurrence was 2.8 (1.3 to 6.2) for recurrent minor strokes, 3.1 (1.9 to 4.6) for nonlacunar stroke, 2.9 (1.3 to 6.8) for MI, and 3.0 (1.4 to 6.4) for hypertension.
In minor ischemic strokes, age, minor disability, MI, nonvalvular atrial fibrillation, and hypercholesterolemia increase the risk of death; recurrent minor strokes, nonlacunar stroke, MI, and hypertension increase the risk of major stroke.
Patent foramen ovale (PFO) is a frequent condition which carries a significant risk for stroke when associated with deep venous thrombosis and primary or secondary coagulation abnormalities. Here, we ...describe a patient in which scuba diving is thought to be associated with stroke in a subject with an otherwise clinically silent PFO.
During a rapid ascent a 43‐year‐old‐scuba diver reported weakness and paresthesias in the right arm which lasted about 10 min. He presented similar symptoms 2 days later 1 h after diving, and a third time on his flight back home.
The MRI showed multiple hyperintense areas on T2‐weighted images in the white matter. Transoesophageal echocardiography (TEE) showed a PFO, whilst all haematological and haemocoagulation tests were negative.
Scuba diving may constitute a patho‐physiological condition in the presence of PFO as breath‐holding promotes right‐to‐left shunt and arterialization of venous bubbles.
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