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Aim: 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. Sample Size Estimates: 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 p = 0.05, two sided. Methods and Design: 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. Study Outcomes: 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. Discussion/Conclusion: 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. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04400981.

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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.

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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.

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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.

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BACKGROUND: Transesophageal echocardiography (TEE) has improved the diagnostic evaluation of ischemic stroke patients, permitting detection of potential cardiac sources of embolism. The present study aimed to evaluate the distribution of potential cardioembolic sources in young versus older stroke patients and their clinical implication for recurrent vascular events. Two hundred and twenty-eight patients with undetermined ischemic stroke were enrolled in the study. METHODS: All patients were submitted to transthoracic and to TEE examination. The mean follow-up period was 43 +/- 19 months. RESULTS: The overall detection of cardiac sources of embolism was significantly higher in younger than in older patients (P = 0.006). Atrial septal abnormalities were more prevalent in the younger than in the older population (P = 0.006), whereas complicated aortic plaques were detected more often in older patients. During the follow-up period of 4-5 years, we identified 40 recurrent stroke episodes or vascular deaths. As expected, there was a significant difference in recurrent vascular events and death of older patients compared to the younger ones (P = 0.025). CONCLUSIONS: The present study demonstrates that atrial septal abnormalities and aortic atheromas are the most prevalent echocardiographic findings in young and elderly stroke patients, respectively. Complicated aortic atheroma is strictly correlated with recurrent cerebral vascular events or death.

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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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