Clinical and Neuroimaging Characteristics in Embolic Stroke of Undetermined versus Cardioembolic Origin: A Population-Based Study.

BACKGROUND AND PURPOSE: Evidence suggests that cardioembolism represents the underlying mechanism in the minority of embolic strokes of undetermined source (ESUS). In this population-based study, we sought to compare the clinical and imaging characteristics as well as outcomes in patients with ESUS and cardioembolic stroke (CE). METHODS: We included consecutive patients with first-ever ischemic stroke (IS) from the previously published population-based Evros-Stroke-Registry identified as ESUS or CE according to standardized criteria. Baseline characteristics, admission NIHSS scores, cerebral edema, hemorrhagic transformation, stroke recurrence, functional outcomes (determined by modified Rankin Scale [mRS] scores), and mortality rates were recorded during the 1-year follow-up period. RESULTS: We identified 21 ESUS (3.7% of IS) and 211 CE (37.1% of IS) cases. Patients with ESUS were younger (median age: 68 years [interquartile range [IQR]: 61-75] vs 80 years [IQR: 75-84]; P < .001), had lower median admission NIHSS scores (4 points [IQR: 2-8] vs 10 points [IQR: 5-17]; P < .001), and lower prevalence of cerebral edema on neuroimaging studies (0 vs. 33.3%, P = .002). Functional outcomes were more favorable in ESUS at 28 (median mRS score: 2 [IQR: 1-3] vs 4 [IQR: 4-5]; P < .001), 90 (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 3-5]; P < .001), and 365 days (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 2-4]; P < 0.001). At 1-year, the mortality rate was lower in ESUS (0% [95% confidence interval [CI]: 0-13.5%] vs 34.6% [95% CI: 28.2-41.0%]; P < .001); the 1-year recurrent rate was also lower numerically (0% [95% CI: 0-13.5%] vs 9.5% [95% CI: 5.5-13.4%]; P = .140) but this difference failed to reach statistical significance due to the small study population. CONCLUSIONS: The clinical and neuroimaging profiles as well as clinical outcomes vary substantially between ESUS and CE indicating different underlying mechanisms.

Incidence, characteristics and outcomes in patients with embolic stroke of undetermined source: A population-based study.

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger (p < .001) and had lower median admission NIHSS-scores (p < .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Stroke recurrence and mortality in northeastern Greece: the Evros Stroke Registry.

Up to date there is no population-based study from Greece providing long-term data on incidence of both all-cause mortality and stroke recurrence for patients with first ever stroke (FES). Adult patients with FES were registered during a 24-month period (2010-2012) and followed-up for 12 months. We calculated cumulative incidences of stroke mortality and recurrence. Univariable and multivariable Cox proportional hazards regression analyses were used to identify independent determinants of 1-year mortality and 1-year stroke recurrence. We prospectively documented 703 first ever stroke cases (mean age 75 ± 12 years; 52.8% males; ischemic stroke 80.8%, intracerebral hemorrhage 11.8%, subarachnoid hemorrhage 4.4%, undefined 3.0%) with a total follow-up time of 119,805 person-years. The cumulative incidence rates of mortality of all FES patients at 28 days, 3 months and 1 year were 21.3% (95% CI 18.5-24.5%), 26% (95% CI 22.9-29.4%) and 34.7% (95% CI 31.3-38.3%), respectively. The risk of 1-year mortality was independently (p < 0.05) associated with advancing age, history of hypertension, increased stroke severity on admission, and hemorrhagic FES type. Cumulative 1-year stroke mortality differed according to both index FES type (ischemic vs. hemorrhage; p < 0.001), but also across different ischemic stroke subtypes (p = 0.025). The cumulative incidence rates of recurrent stroke at 28 days, 3 months and 1 year were 2.0% (95% CI 1.2-3.6%), 4.2% (2.8-6.2%) and 6.7% (5.1-8.8%), respectively. Comparable to other population-based surveys, our study reports 1-year mortality and stroke recurrence rates in patients with FES. These findings highlight the need for effective secondary prevention strategies in a border region of southeastern Europe, which exhibits very high FES incidence rates.

Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.

BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece. METHODS: Adult patients with first-ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classification were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined: 3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and European Standard Population-adjusted incidences of all strokes were 586.8 (95% confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100 000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person-years, respectively. The corresponding European Standard Population-adjusted incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3 (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4% versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for efficient stroke prevention and treatment strategies in Northeastern Greece.

Therapeutic Monoclonal Antibodies and Multiple Sclerosis: The Essentials.

BACKGROUND: Monoclonal antibodies (mAbs) are now established as targeted therapies for malignancies, transplant rejection, autoimmune and infectious diseases. Two monoclonal antibodies are available for treatment and other antibodies are currently being tested in multiple sclerosis (MS) patients. OBJECTIVES: The purpose of the present review paper is to outline the antibody engineering technologies, the immunologic and pharmacologic concepts of mbs and the current status of treatment in MS with emphasis on clinical efficacy and safety. METHOD: We conducted a through review of the scientific literature published until 31 December 2014 (print and electronic publications) concerning the production, applications and side effects of the use of Mabs. Sixty five articles were used in total (both original research and review papers). CONCLUSION: With the introduction of mAbs the treatment of MS has entered a new era, both with respect to efficacy and target specificity. However, administration of mAbs carries the risk of immune reactions such as acute anaphylaxis, serum sickness, infection and other autoimmune diseases. In addition, unexpected consequences arise from our incomplete knowledge of the immune system. For example, natalizumab, a monoclonal antibody targeting α4-integrin on leukocytes increases the risk of developing progressive multifocal leukoencephalopathy, without causing notable immunosuppression. Further study on the use of mabs is required, both in vitro and in the clinical field, in order to increase our knowledge upon these new revolutionary therapeutic agents.