A tool to identify patients with embolic stroke of undetermined source at high recurrence risk

George Ntaios; Georgios Georgiopoulos; Kalliopi Perlepe; Gaia Sirimarco; Davide Strambo; Ashraf Eskandari; Stefania Nannoni; Anastasia Vemmou; Eleni Koroboki; Efstathios Manios; Ana Rodríguez-Campello; Elisa Cuadrado-Godia; Jaume Roquer; Valentina Arnao; Valeria Caso; Maurizio Paciaroni; Exuperio Diez-Tejedor; Blanca Fuentes; Jorge Rodríguez Pardo; Sara Sánchez-Velasco; Antonio Arauz; Sebastian F Ameriso; Lucía Pertierra; Maia Gómez-Schneider; Maximiliano A Hawkes; Miguel A Barboza; Beatriz Chavarria Cano; Ana Maria Iglesias Mohedano; Andrés García Pastor; Antonio Gil-Núñez; Jukka Putaala; Turgut Tatlisumak; Efstathia Karagkiozi; Vasileios Papavasileiou; Konstantinos Makaritsis; Fabio Bandini; Konstantinos Vemmos; Patrik Michel

doi:10.1212/WNL.0000000000008571

A tool to identify patients with embolic stroke of undetermined source at high recurrence risk

Neurology. 2019 Dec 3;93(23):e2094-e2104. doi: 10.1212/WNL.0000000000008571. Epub 2019 Oct 29.

Authors

George Ntaios¹, Georgios Georgiopoulos², Kalliopi Perlepe², Gaia Sirimarco², Davide Strambo², Ashraf Eskandari², Stefania Nannoni², Anastasia Vemmou², Eleni Koroboki², Efstathios Manios², Ana Rodríguez-Campello², Elisa Cuadrado-Godia², Jaume Roquer², Valentina Arnao², Valeria Caso², Maurizio Paciaroni², Exuperio Diez-Tejedor², Blanca Fuentes², Jorge Rodríguez Pardo², Sara Sánchez-Velasco², Antonio Arauz², Sebastian F Ameriso², Lucía Pertierra², Maia Gómez-Schneider², Maximiliano A Hawkes², Miguel A Barboza², Beatriz Chavarria Cano², Ana Maria Iglesias Mohedano², Andrés García Pastor², Antonio Gil-Núñez², Jukka Putaala², Turgut Tatlisumak², Efstathia Karagkiozi², Vasileios Papavasileiou², Konstantinos Makaritsis², Fabio Bandini², Konstantinos Vemmos², Patrik Michel²

Affiliations

¹ From the Department of Internal Medicine (G.N., K.P., E. Karagkiozi, V.P., K.M.), Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Clinical Therapeutics (G.G., A.V., E. Koroboki, E.M., K.V.), Medical School of Athens, Alexandra Hospital, Greece; Stroke Center and Neurology Service (G.S., D.S., A.E., S.N., P.M.), Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Department of Neurology (E.K.), National and Kapodistrian University of Athens, Greece; Division of Brain Sciences (E.K.), Department of Stroke Medicine, Imperial College, London, UK; Stroke Unit (A.R.-C., E.C.-G., J.R.), Department of Neurology, Hospital del Mar, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona, Spain; Stroke Unit (V.A., V.C., M.P.), University of Perugia, Italy; Department of Neurology and Stroke Center (E.D.-T., B.F., J.R.P., S.S.-V.), La Paz University Hospital-Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain; Stroke Clinic (A.A.), Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; Department of Neurology (S.F.A., L.P., M.G.-S., M.A.H.), Institute for Neurological Research, FLENI, Buenos Aires, Argentina; Neurosciences Department (M.A.B.), Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica; Vascular Neurology Section (B.C.C., A.M.I.M., A.G.P., A.G.-N.), Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain; Department of Neurology (J.P., T.T.), Helsinki University Central Hospital and University of Helsinki, Finland; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; Stroke Service (V.P.), Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, UK; and Department of Neurology (F.B.), S. Paolo Hospital, Savona, Italy. gntaios@med.uth.gr.
² From the Department of Internal Medicine (G.N., K.P., E. Karagkiozi, V.P., K.M.), Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Clinical Therapeutics (G.G., A.V., E. Koroboki, E.M., K.V.), Medical School of Athens, Alexandra Hospital, Greece; Stroke Center and Neurology Service (G.S., D.S., A.E., S.N., P.M.), Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland; Department of Neurology (E.K.), National and Kapodistrian University of Athens, Greece; Division of Brain Sciences (E.K.), Department of Stroke Medicine, Imperial College, London, UK; Stroke Unit (A.R.-C., E.C.-G., J.R.), Department of Neurology, Hospital del Mar, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona, Spain; Stroke Unit (V.A., V.C., M.P.), University of Perugia, Italy; Department of Neurology and Stroke Center (E.D.-T., B.F., J.R.P., S.S.-V.), La Paz University Hospital-Autónoma University of Madrid, IdiPAZ Health Research Institute, Spain; Stroke Clinic (A.A.), Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; Department of Neurology (S.F.A., L.P., M.G.-S., M.A.H.), Institute for Neurological Research, FLENI, Buenos Aires, Argentina; Neurosciences Department (M.A.B.), Hospital Dr. Rafael A. Calderón Guardia, CCSS, University of Costa Rica; Vascular Neurology Section (B.C.C., A.M.I.M., A.G.P., A.G.-N.), Stroke Center, Hospital General Universitario Gregorio Marañón, IiSGM Health Research Institute, Universidad Complutense de Madrid, Spain; Department of Neurology (J.P., T.T.), Helsinki University Central Hospital and University of Helsinki, Finland; Department of Clinical Neurosciences (T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; Stroke Service (V.P.), Department of Neurosciences, Leeds Teaching Hospitals NHS Trust and Medical School, University of Leeds, UK; and Department of Neurology (F.B.), S. Paolo Hospital, Savona, Italy.

PMID: 31662492
DOI: 10.1212/WNL.0000000000008571

Abstract

Objective: A tool to stratify the risk of stroke recurrence in patients with embolic stroke of undetermined source (ESUS) could be useful in research and clinical practice. We aimed to determine whether a score can be developed and externally validated for the identification of patients with ESUS at high risk for stroke recurrence.

Methods: We pooled the data of all consecutive patients with ESUS from 11 prospective stroke registries. We performed multivariable Cox regression analysis to identify predictors of stroke recurrence. Based on the coefficient of each covariate of the fitted multivariable model, we generated an integer-based point scoring system. We validated the score externally assessing its discrimination and calibration.

Results: In 3 registries (884 patients) that were used as the derivation cohort, age, leukoaraiosis, and multiterritorial infarct were identified as independent predictors of stroke recurrence and were included in the final score, which assigns 1 point per every decade after 35 years of age, 2 points for leukoaraiosis, and 3 points for multiterritorial infarcts (acute or old nonlacunar). The rate of stroke recurrence was 2.1 per 100 patient-years (95% confidence interval [CI] 1.44-3.06) in patients with a score of 0-4 (low risk), 3.74 (95% CI 2.77-5.04) in patients with a score of 5-6 (intermediate risk), and 8.23 (95% CI 5.99-11.3) in patients with a score of 7-12 (high risk). Compared to low-risk patients, the risk of stroke recurrence was significantly higher in intermediate-risk (hazard ratio [HR] 1.78, 95% CI 1.1-2.88) and high-risk patients (HR 4.67, 95% CI 2.83-7.7). The score was well-calibrated in both derivation and external validation cohorts (8 registries, 820 patients) (Hosmer-Lemeshow test χ²: 12.1 [p = 0.357] and χ²: 21.7 [p = 0.753], respectively). The area under the curve of the score was 0.63 (95% CI 0.58-0.68) and 0.60 (95% CI 0.54-0.66), respectively.

Conclusions: The proposed score can assist in the identification of patients with ESUS at high risk for stroke recurrence.

Publication types

Validation Study

MeSH terms

Adult
Aged
Female
Humans
Intracranial Embolism / complications
Male
Middle Aged
Proportional Hazards Models
Recurrence
Risk Assessment / methods*
Risk Factors
Stroke* / epidemiology
Stroke* / etiology