Study protocol - Prospective case-control trial - Impact of significant carotid stenosis on retinal perfusion measured with automated retinal oximetry.

BACKGROUND: Large vessel carotid stenosis is a significant cause of ischaemic stroke. Indications for surgical revascularisation depend on the severity of the stenosis and clinical symptoms. However, mild symptoms such as TIA (Transient ischaemic attack), amaurosis fugax or minor stroke precede large strokes in only 15% of cases. AIM: The aim of this prospective study is to evaluate whether retinal perfusion is impacted in significant carotid stenosis. Automated retinal oximetry will be used to better assess perfusion in the post-stenotic basin. We presume the more stenotic the blood vessel, the more reduced the retinal perfusion is, resulting in adaptive changes such as greater arteriovenous saturation difference due to greater oxygen extraction. This could broaden the indication spectrum for revascularisation for carotid stenosis. METHODS: We plan to enroll yearly 50 patients with significant carotid stenosis and cross-examine them with retinal oximetry. The study group will provide stenotic vessels and, non-stenotic vessels will form the control group. Patients with significant carotid stenosis will undergo an MRI (Magnetic Resonnance imaging) examination to determine the presence of asymptomatic recent ischaemic lesions in the stenotic basin, and the correlation to oximetry parameters. STATISTICS: The stenosis severity and retinal oximetry parameters will be compared for study and control groups with a threshold of 70%, respectively 80% and 90% stenosis. Results will be then reevaluated with emphasis on MRI findings in the carotid basin. CONCLUSION: This prospective case control study protocol will be used to launch a multicentre trial assessing the relationship between significant carotid stenosis and retinal perfusion measured with automated retinal oximetry. Despite these differences, the findings indicate the potential of retinal oximetry for noninvasive real-time measurements of oxyhaemoglobin saturation in central nervous system vessels. Following calibration upgrade and technological improvement, verification retinal oximetry may potentially be applied to critically ill and anaesthesia care patients. The study on combined scanning laser ophthalmoscope and retinal oximetry supports the feasibility of the technique for oximetry analysis in newly born babies. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06085612.

Socioeconomic status and lifestyle in young ischaemic stroke patients: a possible relationship to stroke recovery and risk of recurrent event.

OBJECTIVES: Socioeconomic status (SES) and lifestyle have impact on recovery after ischaemic stroke (IS) and on risk of recurrent ischaemic stroke (RIS) in elderly patients. With regard to currently available limited data on young people, we aimed to assess SES and parameters of lifestyle and evaluate their relationship to stroke recovery and risk of RIS in young patients. METHODS: We analysed consecutive young IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischaemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). Data were acquired from structured a self-evaluating multiple-choice questionnaire. Clinical outcome was assessed using the Modified Rankin Scale (MRS) after 3 months with score 0-1 for excellent outcome. RESULTS: Data were obtained from 297 (163 males, mean age 39.6 ± 7.8 years) young patients. Patients with MRS 0-1 (237, 79.8%) did not differ in SES except university education (21.1 vs. 3.3%; p = 0.001), less smoked (16.5 vs. 58.3%; p < 0.001), more of them did regular sport activities (79.1 vs. 51.6%; p = 0.02) and passed regular preventive medical checks (45.6 vs. 24.2%; p = 0.01). Twelve (4%) patients suffered from RIS during a follow-up with median of 25 months. They did not differ in SES but had higher body mass index (31.6 vs. 26.7; p = 0.007), reported less regular sport activities (16.7 vs. 73.0%; p < 0.001) and less regular medical checks (8.3 vs. 40.0%; p = 0.001). CONCLUSION: In young patients, SES had no relationship to clinical outcome after IS and to risk of RIS except education level. Some parameters of health lifestyle were presented more in patients with excellent outcome and without RIS during the follow-up.

Brain Imaging Findings and Response to Intravenous Thrombolysis in Posterior Circulation Stroke.

INTRODUCTION: Intravenous thrombolysis (IVT) is a standard treatment for both anterior circulation ischaemic stroke (ACIS) and posterior circulation ischaemic stroke (PCIS). Our aim was to evaluate the predictors for a good clinical outcome and intracerebral haemorrhage (ICH) in patients undergoing posterior circulation IVT based on the initially performed CT or MR imaging. METHODS: The study cohort consisted of 1643 consecutive patients with acute ischaemic stroke (1440 ACIS, 203 PCIS cases) who underwent IVT. ICH was classified according to the European Cooperative Acute Stroke Study (ECASS) I protocol. Clinical outcome was assessed using the modified Rankin scale (mRS). Early ischaemic signs and pre-existing structural signs were assessed. RESULTS: Good clinical outcomes (mRS 0-1) were noted in 45.3% of patients with PCIS, with a mortality rate of 14.8%. ICH was noted in 8.3%, and a large haemorrhage was found in 2.4% of patients. Some early ischaemic signs and pre-existing structural signs on initial CT/MR imaging correlated significantly with the 90-day clinical outcome. CONCLUSIONS: Early ischaemic signs and pre-existing structural signs should be considered during the assessment of patients with PCIS eligible for IVT. Tissue hypoattenuation on initial CT scans correlates with an increased risk of death. Similarly to anterior circulation, atrophy on initial MRI may negatively predict good clinical outcome in posterior circulation.

Arterial Hypertension and Risk of Recurrent Event in Young Ischemic Stroke Patients.

INTRODUCTION: In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients. METHODS: The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification. RESULTS: Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510-24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000). CONCLUSION: AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.

Young cryptogenic ischemic stroke: A descriptive analysis of clinical and laboratory characteristics, outcomes and stroke recurrence.

BACKGROUND AND PURPOSE: Ischemic strokes (IS) occur also in young adults and despite an extensive work-up the cause of IS remains very often cryptogenic. Thus, effectiveness of secondary prevention may be unclear. We aimed to analyze a relationship among vascular risk factors (VRF), clinical and laboratory parameters, outcomes and recurrent IS (RIS) in young cryptogenic IS (CIS) patients. SUBJECTS AND METHODS: The study set consisted of young acute IS patients < 50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). All analyzed patients underwent transesophageal echocardiography, 24-h and 3-week ECG-Holter to assess cause of IS according to the ASCOD classification. Recurrent IS (RIS) was recorded during a follow-up (FUP). RESULTS: Out of 294 young enrolled patients, 208 (70.7%, 113 males, mean age 41.6 ± 7.2 years) were identified as cryptogenic. Hyperlipidemia (43.3%), smoking (40.6%) and arterial hypertension (37.0%) were the most frequent VRF. RIS occurred in 7 (3.4%) patients during a mean time of FUP 19 ± 23 months. One-year risk of RIS was 3.4% (95%CI: 1.4-6.8%). Patients with RIS were older (47.4 vs. 41.1 years, p = 0.007) and more often obese (71.4 vs. 19.7%, p = 0.006), and did not differ in any of other analyzed parameters and VRF. Multivariate logistic regression analysis showed obesity (OR: 9.527; 95%CI: 1.777-51.1) and the previous use of antiplatelets (OR: 15.68; 95%CI: 2.430-101.2) as predictors of recurrent IS. CONCLUSION: Despite a higher presence of VRF in young CIS patients, the risk of RIS was very low. Obesity and previous use of antiplatelet therapy were found the only predictors of RIS.

Risk of recurrent ischemic stroke in young cryptogenic patients with embolic stroke of undetermined source.

INTRODUCTION: Elderly cryptogenic ischemic stroke (IS) patients with embolic stroke of undetermined source (ESUS) have a high risk of recurrent IS (RIS) compared to other stroke subtypes. In young ESUS patients, different sources of embolism may be a cause and the risk of RIS remains not enough established. The aim was to assess and compare risk of RIS between ESUS and non ESUS patients <50 years. METHODS: The study set consisted of young acute IS patients <50 years enrolled in the prospective HISTORY (Heart and Ischemic STrOke Relationship studY) study registered on ClinicalTrials.gov (NCT01541163). In all analyzed patients, the brain ischemia was confirmed on CT or MRI. All patients underwent identical diagnostic protocol including TEE and long-term ECG-Holter. Cause of IS was assessed according to the ASCOD classification. RESULTS: Of 320 enrolled patients <50 years, 219 (68.4%) were identified as cryptogenic (119 males, mean age 41.4 ±â€¯7.2 years) and 122 (38.1%) patients fulfilled the ESUS criteria. During the follow-up with a median of 34 months, three (2.5%) ESUS and 5 (5.2%) non-ESUS patients suffered from RIS (p = .471). One-year risk of RIS was 0.008 (95% CI: 0-0.025) for ESUS and 0.036 (95% CI: 0-0.076) for non-ESUS patients (p = .262). CONCLUSION: The risk of RIS was very low in ESUS patients and did not differ from those with non-ESUS. Our finding may indicate that antiplatelet therapy can be effective in the secondary prevention in young ESUS patients if high-risk sources of embolization are excluded extensively.

Low Levels of Glycemia within the First 48 Hours after Mechanical Thrombectomy for Acute Ischemic Stroke May be Associated with Better Clinical Outcome.

INTRODUCTION: Many different factors may have an impact on clinical outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We aimed to investigate levels of serum glycemia (GLY) within the first 48 hours after MT. SUBJECTS AND METHODS: Consecutive AIS patients were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale with a score 0-2 for good outcome. Presence of symptomatic intracerebral hemorrhage was assessed according to the SITS- MOST criteria. RESULTS: In total, 868 patients (442 males, mean age 69.7 ± 12.2 years) with a median of admission NIHSS 17 points were enrolled in the study and 253 (29.1%) of them were diabetics. Recanalization was reached in 758 (87.3%) patients. Patients with good outcome (412, 47.5%) had lower median of GLY (6.5 versus 7.4 mmol/L, P < .0001) within the first 48 hours after MT. Similar results were found also in diabetics (8.1 versus 9.6 mmol/L, P < .0001) and in patients with achieved recanalization (6.5 versus 7.5 mmol/L, P < .0001). Multivariate regression analysis with adjustment for potential confounders showed median of GLY (P = .0001, odds ratio: 0.830, 95% confidence interval: 0.755-0.913) as a predictor of good outcome after MT. CONCLUSION: Lower levels of GLY within the first 48 hours after MT may be associated with better functional outcome after 3 months.

Impact of blood pressure levels within first 24 hours after mechanical thrombectomy on clinical outcome in acute ischemic stroke patients.

INTRODUCTION: Despite early management and technical success of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), not all patients reach a good clinical outcome. Different factors may have an impact and we aimed to evaluate blood pressure (BP) levels in the first 24 hours after MT. METHODS: Consecutive AIS patients treated with MT were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale (mRS) with a score 0-2 for good outcome. The presence of symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria. RESULTS: Of 703 treated patients, completed BP levels were collected in 690 patients (350 males, mean age 71±13 years) with median of admission NIHSS 17 points. Patients with mRS 0-2 had a lower median of systolic BP (SBP) compared with those with poor outcome (131 vs 140 mm Hg, P<0.0001). The rate of SICH did not differ between the patients with a median of SBP <140 mm Hg and ≥140 mm Hg. (5.1% vs 5.1%, P=0.980). Multivariate regression analysis with adjustment for potential confounders showed a median of distolic BP (P=0.024, OR: 0.977, 95% CI: 0.957 to 0.997) as a predictor of good functional outcome after MT, and a median of maximal SBP (P=0.038; OR: 0.990, 95% CI: 0.981 to 0.999) in the patients with achieved recanalization. CONCLUSION: Lowering of BP within the first 24 hours after MT may have a positive impact on clinical outcome in treated patients.

Author Correction: Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke.

In the original publication of the article, there was a switched order of author names.

Mechanical Thrombectomy in Patients with Acute Ischemic Stroke on Anticoagulation Therapy.

INTRODUCTION/PURPOSE: Mechanical thrombectomy (MT) for acute ischemic stroke (IS) can be performed also in patients on anticoagulation therapy (AT); however, sufficient and reliable data about safety and efficacy of MT are still missing. Thus, we aimed to compare these parameters between patients treated on AT and without AT. MATERIALS AND METHODS: All consecutive IS patients treated with MT using stent retrievers were included in the retrospective analysis. Neurological deficit was scored using National Institutes of Health Stroke Scale (NIHSS) and 90-day clinical outcome using modified Rankin scale with a score 0-2 for good outcome. Recanalization was rated using Thrombolysis in Cerebral Infarction (TICI) scale. Symptomatic intracerebral hemorrhage (SICH) was assessed according to the SITS-MOST criteria. RESULTS: Out of 703 patients treated with MT, 88 (12.5%) patients (46% males, mean age 75.5 ± 11.8 years) were on AT with an admission median NIHSS of 17 points. Recanalization (TICI 2b-3) was achieved in 80% and complete (TICI 3) in 65% of patients on AT and in 80 and 65% of patients without AT (p-1.000). SICH after MT was detected in 9% of AT and 5% of non-AT patients (p-0.136). Good outcome was present in 36% of AT patients (p-0.03). AT patients with poor outcome had more frequently atrial fibrillation (93%, p-0.005), higher admission NIHSS (17, p-0.004) and higher rate of SICH (14.5%, p-0.047). CONCLUSION: MT seems to be safe also in patients on AT. Poor outcome may be related to higher admission NIHSS, higher rate of SICH and presence of atrial fibrillation.

Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in Posterior Circulation Stroke.

Intravenous thrombolysis (IVT) is a standard treatment for anterior (ACS) and posterior circulation stroke (PCS). However, due to the low occurrence of PCS and of intracranial hemorrhage (ICH) in PCS, the knowledge about ICH predictors following IVT in PCS is sparse. Our aim was to identify predictors for ICH following IVT in PCS. The set consisted of 1281 consecutive ischemic stroke (IS) patients treated with IVT, out of which 158 (103 males; mean age 65.6 ± 12.3 years) had PCS. Collected data include baseline characteristics, common stroke risk factors, pre-medication, stroke severity, admission blood glucose level, blood pressure and treatment with intravenous antihypertensive therapy before and during IVT, occlusion of arteries, recanalization rate, time to treatment, and clinical outcome at day 90. Overall, 11 (7%) patients had ICH. Atrial fibrillation (p = 0.004), neurological deficit at time of treatment in the National Institutes of Health Stroke Scale (p = 0.016), decreased level of consciousness (p = 0.003), occlusion of basilar artery (p = 0.007), occlusion of PCA (p = 0.001), and additional endovascular therapy (p = 0.001) were identified by logistic regression analysis as significant predictors for ICH in PCS. Patients with ischemic lesion in the brainstem, occlusion of vertebral artery, or absence of basilar and posterior cerebral artery occlusion might be considered for treatment with IVT even in borderline cases. Those patients seem to have less frequently favorable outcomes without an increase in ICH rate. Time to IVT in PCS seems not to influence ICH risk or chances for favorable outcomes as significantly as it does in ACS.