The effect of repeated remote ischemic postconditioning after an ischemic stroke (REPOST): A randomized controlled trial.

BACKGROUND AND AIMS: A potential strategy to treat ischemic stroke may be the application of repeated remote ischemic postconditioning (rIPostC). This consists of several cycles of brief periods of limb ischemia followed by reperfusion, which can be applied by inflating a simple blood pressure cuff and subsequently could result in neuroprotection after stroke. METHODS: Adult patients admitted with an ischemic stroke in the past 24 h were randomized 1:1 to repeated rIPostC or sham-conditioning. Repeated rIPostC was performed by inflating a blood pressure cuff around the upper arm (4 × 5 min at 200 mm Hg), which was repeated twice daily during hospitalization with a maximum of 4 days. Primary outcome was infarct size after 4 days or at discharge. Secondary outcomes included the modified Rankin Scale (mRS)-score after 12 weeks and the National Institutes of Health Stroke Scale (NIHSS) at discharge. RESULTS: The trial was preliminarily stopped after we included 88 of the scheduled 180 patients (average age: 70 years, 68% male) into rIPostC (n = 40) and sham-conditioning (n = 48). Median infarct volume was 2.19 mL in rIPostC group and 5.90 mL in sham-conditioning, which was not significantly different between the two groups (median difference: 3.71; 95% CI: -0.56 to 6.09; p = 0.31). We found no significant shift in the mRS score distribution between groups. The adjusted common odds ratio was 2.09 (95% CI: 0.88-5.00). We found no significant difference in the NIHSS score between groups (median difference: 1.00; 95% CI: -0.99 to 1.40; p = 0.51). CONCLUSION: This study found no significant improvement in infarct size or clinical outcome in patients with an acute ischemic stroke who were treated with repeated remote ischemic postconditioning. However, due to a lower-than-expected inclusion rate, no definitive conclusions about the effectiveness of rIPostC can be drawn.

The Hyperintense study: Assessing the effects of induced blood pressure increase and decrease on MRI markers of cerebral small vessel disease: Study rationale and protocol.

Background: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels. Methods: Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18-55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn (T = 1), when patients have restarted medication (T = 2) and reached target blood pressure and 1 year later (T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling. Discussion: The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.

Prevalence, risk factors, and long-term outcomes of cerebral ischemia in hospitalized COVID-19 patients - study rationale and protocol of the CORONIS study: A multicentre prospective cohort study.

Background: COVID-19 is often complicated by thrombo-embolic events including ischemic stroke. The underlying mechanisms of COVID-19-associated ischemic stroke, the incidence and risk factors of silent cerebral ischemia, and the long-term functional outcome in these patients are currently unknown. Patients and methods: CORONavirus and Ischemic Stroke (CORONIS) is a multicentre prospective cohort study investigating the prevalence, risk factors and long-term incidence of (silent) cerebral ischemia, and the long-term functional outcome among patients with COVID-19. We aim to include 200 adult patients hospitalized with COVID-19 without symptomatic ischemic stroke to investigate the prevalence of silent cerebral ischemia compared with 60 (matched) controls with MRI. In addition, we will identify potential risk factors and/or causes of cerebral ischemia in COVID-19 patients with (n = 70) or without symptomatic stroke (n = 200) by means of blood sampling, cardiac workup and brain MRI. We will measure functional outcome and cognitive function after 3 and 12 months with standardized questionnaires in all patients with COVID-19. Finally, the long-term incidence of (new) silent cerebral ischemia in patients with COVID-19 will be assessed with follow up MRI (n = 120). Summary: The CORONIS study is designed to add further insight into the prevalence, long-term incidence and risk factors of cerebral ischemia, and the long-term functional outcome in hospitalized adult patients with COVID-19.

The prognostic value of extracranial vascular characteristics on procedural duration and revascularization success in endovascularly treated acute ischemic stroke patients.

Introduction: Vascular anatomy might affect endovascular treatment success in acute ischemic stroke patients with large vessel occlusion. We investigated the prognostic value of extracranial vascular characteristics on procedural time and revascularization success in patients with large vessel occlusion in the anterior cerebral circulation. Patients and methods: We included 828 patients endovascularly treated within 6.5 hours of symptom onset from the Dutch MR CLEAN-Registry. We evaluated aortic arch configuration, stenosis and tortuosity of supra-aortic arteries, and internal carotid arteries (ICAs) on pre-intervention CTA. We constructed logistic prediction models for outcome variables procedural duration (≥60 minutes) and non-successful revascularization (extended thrombolysis in cerebral infarction (eTICI) of 0-2A) using baseline characteristics and assessed the effect of extracranial vascular characteristics on model performance. Results: Cervical ICA tortuosity and stenosis ≥99% improved prediction of long procedural duration compared with baseline characteristics from area under the curve of 0.61 (95% CI: 0.57-0.65) to 0.66 (95% CI: 0.62-0.70) (P < 0.001). Cervical ICA tortuosity was significantly associated with non-successful recanalization. Prediction of non-successful revascularization did not improve after including aortic arch elongation, acute take-off angle, aortic variant, origin stenosis of supra-aortic arteries, and cervical ICA tortuosity, with an area under the curve of 0.63 (95% CI: 0.59-0.67) compared with 0.59 (95% CI: 0.55-0.63) (P = 0.11). Conclusion: Extracranial vascular characteristics have additional prognostic value for procedural duration, but not for revascularization success, compared with baseline characteristics. Performance of both prediction models is limited in patients treated for large vessel occlusion.

Long term cerebral and vascular complications after irradiation of the neck in head and neck cancer patients: a prospective cohort study: study rationale and protocol.

BACKGROUND: Successful treatment options for cancer result in more young long-term survivors prone for long-term complications. Carotid artery vasculopathy is a potential long-term complication after radiotherapy of the neck, resulting in cerebrovascular events and probably deficits in cognitive and motor functioning. Better insight into the underlying pathofysiology of radiotherapy induced carotid artery vasculopathy is needed for prognostic purposes and to develop preventive strategies. METHODS/DESIGN: The current study is a prospective cohort study on the long-term cerebral and vascular complications after radiotherapy of the neck, in 103 patients treated for head and neck cancer, included in our study database between 2002 and 2008. Baseline protocol (before radiotherapy) included screening for cerebrovascular risk factors and intima media thickness measurement of carotid arteries by ultrasonography. Follow-up assessment more than 5 years after radiotherapy included screening of cerebrovascular risk factors, cerebrovascular events, neurological examination with gait and balance tests, extensive neuropsychological examination, self-report questionnaires, ultrasonography of the carotid arteries with measurement of intima media thickness and elastography, magnetic resonance imaging of the brain and magnetic resonance angiography of the carotid arteries. DISCUSSION: The current study adds to the understanding of the causes and consequences of long-term cerebral and vascular changes after radiotherapy of the neck. These data will be helpful to develop a protocol for diagnostic and preventive strategies for long-term neurological complications in future head and neck cancer patients with anticipated radiotherapy treatment.