Israel Medical Association Journal

Background: Ischemic stroke is associated with increased risk of morbidity and mortality in future vascular events.

Objectives: To investigate whether CHA₂DS₂-VASc scores aid in risk stratification of middle-aged patients without atrial fibrillation (AF) experiencing ischemic stroke.

Methods: We analyzed data of 2628 patients, aged 40–65 years with no known AF who presented with acute ischemic stroke between January 2020 and February 2022. We explored the association between CHA₂DS₂-VASc scores categorized by subgroups (score 2–3, 4–5, or 6–7) with major adverse cardiac and cerebrovascular events (MACCE) including recurrent stroke, myocardial infarction, coronary revascularization, or all-cause death during a median follow-up of 19.9 months.

Results: Mean age was 57 years (30% women); half were defined as low socioeconomic status. Co-morbidities included hypertension, diabetes, obesity, and smoking in 40–60% of the patients. The incidence rate of MACCE per 100 person-years was 6.7, 12.2, and 21.2 in those with score 2–3, 4–5, and 6–7, respectively. In a multivariate cox regression model, compared to patients with score 2–3 (reference group), those with score 4–5 and 6–7 had an adjusted hazard ratio (95% confidence interval [95%CI]) for MACCE of 1.74 (95%CI 1.41–2.14) and 2.87 (95%CI 2.10–3.93), respectively. The discriminative capacity of CHA₂DS₂-VASc score for overall MACCE was modest (area under curve 0.63; 95%CI 0.60–0.66), although better for myocardial infarction 0.69 (95% CI 0.61–0.77).

Conclusions: CHA₂DS₂-VASc score may predict future MACCE in middle-aged patients with ischemic stroke and no history of AF.

Background: The two cerebral hemispheres influence the immune response differently. While the left hemisphere enhances cellular immunity, the right hemisphere inhibits it.

Objectives: To determine whether immune and inflammatory markers correlated with stroke severity and hospitalization duration as a function of stroke side.

Methods: The study included 137 patients with unilateral ischemic stroke. The medical records were reviewed for demographic and clinical laboratory data, including C-reactive protein (CRP), white blood cell (WBC) count, its differential stroke side and stroke severity according to the National Institute of Health Stroke Scale (NIHSS), and length of hospital stay (LOS). We examined differences between right side (RS) and left side (LS) stroke on immune and inflammatory markers and compared correlations between these markers and NIHSS and LOS as a function of stroke side.

Results: RS stroke patients had higher CRP and monocytes than LS stroke patients. In RS stroke patients, CRP, total WBC, and lymphocyte levels positively correlated with both NIHSS and LOS, whereas levels of neutrophils were positively correlated with NIHSS alone. No correlations were found for LS stroke patients.

Conclusions: Immune-inflammatory markers correlated with stroke severity and LOS only in patients with RS stroke. Neuroimmunological processes influence short-term clinical outcomes after stroke, especially considering the differential effects of the hemispheres on immunity. Prospective studies that evaluate long-term clinical outcomes are needed. Testing the effects of anti-inflammatory treatments on prognosis of RS stroke patients should be considered.

Background: Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease and stroke. Metformin is an old, relatively safe, first line therapy for T2DM; however, it has been associated with stroke.

Objectives: To study the effects of metformin use and vitamin B12 deficiency on stroke rate among patients with T2DM.

Methods: We conducted a prospective study of patients admitted with ischemic stroke within 12 months (starting March 2020). We studied the clinical impact of metformin on vitamin B12 deficiency and stroke evolution. Student's t-test and ANOVA were used to compare the groups of patients and to determine whether there was any direct or indirect effect of metformin use on vitamin B12 deficiency and stroke.

Results: In total, 80 patients were admitted with ischemic stroke. Clinical status and biochemical data were collected and compared with healthy volunteers. There were 39 diabetic patients, 16 took metformin for at least 1 year. Among those who took metformin for at least 1 year, 9 had vitamin B12 level < 240 pg/ml (56.2%); 23 diabetic patients did not get metformin and only 4 had vitamin B12 level < 240 pg/ml (17.4%) (P = 0.014).

Conclusions: T2DM is a significant risk factor to the development of ischemic stroke. We found an association between metformin use and vitamin B12 deficiency and an association between vitamin B12 deficiency and stroke risk in patients with T2DM. Diabetic patients who are taking metformin should monitor their vitamin B12 level.

Endovascularly retrieved clots may be a potential resource for diagnosing stroke etiology. This method may influence secondary prevention treatment. We measure thrombin activity eluted by serially washing clots. We concluded that an assay measuring the change in thrombin in clots retrieved during acute stroke endovascular thrombectomy procedures may serve as a diagnostic marker of the origin of the clot. The suggested mechanism for these differences may be the clot location before its retrieval, with high blood flow causing thrombin washout in atherosclerotic clots, in contrast to atrium appendage low blood flow retaining high thrombin levels.

Atrial fibrillation is becoming an increasingly important problem in cardio-oncology. Specific risk factors for atrial fibrillation occurrence include type of cancer disease and anticancer drugs. Anticoagulation is often abandoned. The CHA₂DS₂-VASc and CHA₂DS₂ scores may be important not only in predicting stroke but also in mortality. The role of new direct oral anticoagulants is growing, but they need to be used in a personalized approach depending on the risk of unbeneficial interactions with cancer treatment and the risk of bleeding.

Background: Falls are a common complication in persons with stroke (PwS). Reliable assessment of balance responses to unexpected loss of balance has the potential to identify risk for falls. 

Objectives: To examine inter-observer reliability of balance responses to unannounced surface perturbations in PwS and to explore the concurrent validity of a balance recovery assessment protocol.

Methods: Two observers evaluated balance recovery strategies and fall threshold (a fall into a harness system) in 15 PwS and 15 healthy adults who were exposed to forward, backward, right, and left unannounced surface translations in six increasing intensities while standing. 

Results: Observer agreement was 100% for the fall threshold. Kappa coefficients for step strategies were 0.960–0.988 in PwS and 0.886–0.938 in healthy adults, 0.905–0.988 for arm reactions in PwS and 0.754–0.926 in healthy adults. Significant correlations were found between fall threshold and Berg Balance Scale (r = 0.691), 6-minute walk test (r = 0.599), and fall efficacy scale-international (r= -0.581). 

Conclusions: A trained examiner can reliably classify reactive balance responses to surface perturbations. The high frequency of falls observed in PwS highlights the importance of assessing reactive balance responses to different directions and intensities of surface translations.

Aortic stenosis (AS) is a common valvular pathology and is increasing in prevalence. Severe symptomatic AS is associated with serious outcomes if left untreated. Transcatheter aortic valve implantation (TAVI) is an innovative modality, which has revolutionized the treatment of AS. With growing experience and technological upgrades, TAVI has become a valid alternative to surgical valve replacement. However, TAVI is associates with increase non-negligible risks of mortality, stroke, physical disability, and healthcare expenditures. Furthermore, imaging modalities have shown new ischemic lesions in most patients following TAVI (silent strokes), which might be related to worse subsequent neurocognitive function. Embolic protective devices are emerging as a safe, technically feasible implements to reduce the burden of periprocedural thromboembolism, and have shown promising results of improved clinical outcomes.

Background: Endothelial progenitor cells may have a role in ongoing endothelial repair. Impaired mobilization or depletion of these cells may contribute to progression of vascular disease. Our hypothesis was that endothelial progenitor cells would be suppressed in patients with acute cerebrovascular event based on our previous study that found severe endothelial dysfunction in those patients.

Objectives: To study the ability of patients with acute stroke to build colonies of endothelial progenitor cells.

Methods: We studied the number of colony-forming units of endothelial progenitor cells (CFU-EPCs) from the peripheral blood of 22 male patients with a first-time acute stroke (age 58.09 ± 9.8 years) and 13 healthy men (34 ± 6.7 years), 8 female patients with a first-time acute stroke (54.6 ± 10.3 years) and 6 healthy women (38.3 ± 11.6 years). Endothelium-dependent function was assessed by high-resolution ultrasonography of the brachial artery that measured the change in diameter of the artery by flow-mediated diameter percent change (FMD%). All patients had strokes demonstrated by a brain computed tomography (CT) scan done on admission. Peripheral blood was drawn soon after admission and was processed for endothelial progenitor cells in culture.

Results: Thirty patients without known cardiovascular risk factors and who did not take any medications were admitted with a first-time acute stroke. All demonstrated a strong correlation between CFU-EPCs grown in culture and endothelial dysfunction (r = 0.827, P < 0.01). Endothelial dysfunction with an FMD% of -2.2 ± 9.7% was noted in male patients vs. 17.5 ± 6.8% in healthy males (P = 0.0001), and -7.2 ± 10.1% in female patients vs. 25.1 ± 7.1% in healthy females (P = 0.0001). CFU-EPCs were 5.5 ± 6.3 in men with stroke vs. 23.75 ± 5.3 in healthy males (P = 0.0001), and 7.6 ± 4.9 in women with stroke vs. 22.25 ± 6.7 in healthy females (P = 0.0004).

Conclusions: Patients with acute stroke had an impaired ability to grow CFU-EPCs in culture and exhibited endothelial dysfunction. The novelty of this study was the discovery of the phenomenon of depressed numbers of EPCs and the poor ability to grow colonies of EPCs in the first 24 hours of the cerebrovascular event.

Background: Stroke is a major cause of death in the western world, and carotid endarterectomy has been shown to be effective in treating both symptomatic and asymptomatic carotid stenosis. Carotid stenting is a relatively new form of treatment for carotid stenosis and few studies have looked specifically at asymptomatic patients.

Objectives: To retrospectively examine short- and long-term results in the treatment of asymptomatic carotid artery stenosis with surgery or stenting.

Methods: We retrospectively collected data of all patients with asymptomatic carotid stenosis treated by carotid artery stenting or carotid endarterectomy in our department from 2006–2007. The primary endpoints were stroke, myocardial infarction, or death during the periprocedural period; or any ipsilateral stroke, restenosis, or death within 4 years after the procedure.

Results: The study comprised 409 patients who were treated by either stenting or surgery. There was a low morbidity rate in both treatment groups with no significant difference in morbidity or mortality between the treatment groups in both in the short-term as well as long-term.

Conclusion: Both treatment methods have a low morbidity and mortality rate and should be considered for patients with few risk factors and a long life expectancy. Treatment method should be selected according to the patient's individual risk factors and imaging data.

Background: Atrial fibrillation (AF) is the most common arrhythmia and a common cause of ischemic stroke. Stroke patients with AF have been shown to have a poorer neurological outcome than stroke patients without AF.

Objectives: To determine the impact of pre-existing AF on residual degree of disability in patients treated with IV thrombolysis.

Methods: In this case-control study, data of 214 stroke patients (63 with AF and 151 without AF) were collected from the National Acute Stroke Israeli Registry, a nationwide quadrennial stroke database. Stroke severity and outcome were compared using the National Institute of Health Stroke Scale (NIHSS) on admission and the modified Rankin Scale (mRS) on admission and discharge. Demographics and stroke characteristics were also compared between the groups.

Results: Stroke severity, as determined by NIHSS at admission, was higher in the AF group than the non-AF. In the group of patients who were treated with intravenous tissue plasminogen activator (tPA), more patients had favorable outcomes (mRS = 0–1 on discharge) in the non-AF group than in the AF group (P = 0.058, odds ratio = 2.217, confidence interval 0.973 to 5.05).

Conclusions: Our study suggests worse outcome in thrombolized patients with AF compared to non-AF stroke patients. Therefore, AF itself can be a poor prognostic factor for tPA sensitivity regarding the chance of revascularization and recovery after intravenous tPA.