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2020, Number 2

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Rev Cubana Neurol Neurocir 2020; 10 (2)

Diagnostic and therapeutic algorithm in embolic stroke of undetermined cause

Morales CE, Vargas AGA, Bustamante SA

Language: Spanish
References: 54
Page: 1-27
PDF size: 607.64 Kb.


ABSTRACT

Objective: To describe a diagnostic algorithm that facilitates individualizing the pillars of secondary prophylaxis in patients with indeterminate embolic stroke.
Acquisition of evidence: A systematic review of the studies published from 2014 to 2019 on the clinical, imaging and therapeutic aspects of the spectrum of indeterminate embolic stroke was carried out. We consulted Medline (PubMed), SciELO, Cochrane and Google Scholar databases. Original articles, published in peer-reviewed journals, which included patients older than 18 years with an indeterminate embolic infarction diagnosis were taken into account.
Results: Indeterminate embolic stroke represents 21% of cerebral infarcts in people younger than 50 years. It is defined as a non-lacunar infarct, with no evidence of significant arterial stenosis or cardioembolic source. Mild cortical infarcts associated with paradoxical embolism are more likely in young people without vascular risk factors. In advanced ages, cardiac embolism and the artery-artery mechanism predominate due to cervical and aortic substenotic plaques. Two opposite etiological phenotypes are distinguished: those with an atherothrombotic substrate and white thrombus formation that benefit from antiaggregation, and those due to the production of red thrombi where anticoagulation is the therapy of choice.
Conclusions: Including indeterminate embolic strokes, as a clinical phenotype, makes it possible to perform a stratified diagnostic algorithm with more advanced complementary tests in patients who suffer from it, to reduce the cases that remain cryptogenic. However, these patients represent a large and heterogeneous group that does not allow generalization of the use of anticoagulation.


REFERENCES

  1. Tsivgoulis G, Patousi A, Pikilidou M, Birbilis T, Katsanos AH, Mantatzis M, et al. Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry. Stroke. 2018;49:1-29. Doi: 10.1161/STROKEAHA.117.019524.

  2. Andreas Charidimou. Age and the fuzzy edges of embolic stroke of undetermined source: Implications for trials. Neurology. 2017;89:1-2. Doi: 10.1212/WNL.0000000000004220

  3. Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke. 2017;48:867-72.

  4. Kamel H, Healey JS. Cardioembolic Stroke. Circ Res. 2017;120(3):514-26.

  5. Marnane M, Duggan CA, Sheehan OC, Merwick A, Hannon N, Curtin D, et al. Stroke subtype classification to mechanism-specific and undetermined categories by TOAST, A-SC-O, and causative classification system: direct comparison in the North Dublin population stroke study. Stroke. 2010;41:1579-86. Doi: 10.1161/STROKEAHA.109.575373.

  6. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35-41.

  7. Tsivgoulis G, Katsanos AH, Köhrmann M, Caso V, Lemmens R, Tsioufis K, et al. Embolic strokes of undetermined source: theoretical construct or useful clinical tool? Ther Adv Neurol Disord. 2019;12:1-12. Doi: https://doi.org/10.1177/175628

  8. Schöberl F, Ringleb PA, Wakili R, Poli S, Wollenweber FA, Kellert L. Juvenile stroke—a practice-oriented overview. Dtsch Arztebl Int. 2017;114:527-34. Doi: 10.3238/arztebl.2017.0527

  9. Ay H, Benner T, Arsava EM, Furie KL, Singhal AB, Jensen MB, et al. A computerized algorithm for etiologic classification of ischemic stroke: the causative classification of stroke system. Stroke. 2007;38:2979-84.

  10. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, et al. Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13:429-38. Doi: 10.1016/S1474-4422(13)70310-7.

  11. Molina-Seguin J, Vena AB, Colàs-Campàs L, Benalbdelhak I, Purroy F. Revisión sistemática de las características y pronóstico de los sujetos que sufren un ictus criptogénico no lacunar de mecanismo embólico. Rev Neurol. 2018;66(10):325-30.

  12. Ntaios G, Perlepe K, Lambrou D, Sirimarco G, Strambo D, Eskandari A, et al. Prevalence and Overlap of Potential Embolic Sources in Patients With Embolic Stroke of Undetermined Source. J Am Heart Assoc. 2019;8:e012858. Doi: 10.1161/JAHA.119.012858.

  13. Ntaios G, Papavasileiou V, Milionis H, Makaritsis K, Manios E, Spengos K, et al. Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis. Stroke. 2015;46:176-81.

  14. Perera KS, Vanassche T, Bosch J, Giruparajah M, Swaminathan B, Mattina KR, et al. Embolic strokes of undetermined source: Prevalence and patient features in the ESUS Global Registry. International Journal of Stroke 2016;11(5):526-33. Doi: 10.1177/1747493016641967

  15. Rodríguez FL, Ameriso SF. Accidente cerebrovascular embólico de origen indeterminado. El concepto ESUS. Neurol Arg. 2017;387(X):1-5. Doi: https://doi.org/10.1016/j.neuarg.2017.11.004

  16. Perera KS, Swaminathan B, Veltkamp R, Arauz A, Ameriso S, Mar Fabregas J, et al. Frequency and features of embolic stroke of undetermined source in young adults. European Stroke Journal. 2018;3(2):110-6. Doi: 10.1177/2396987318755585

  17. Cantú-Brito C, Sampaio GS, Ameriso SF. Embolic Stroke of Undetermined Source in Latin America A Review. The Neurologist. 2017;22:171-81.

  18. Katsanos AH, Bhole R, Frogoudaki A, Giannopoulos S, Goyal N, Vrettou AR, et al. The value of transesophageal echocardiography for embolic strokes of undetermined source. Neurology. 2016;87:988-95.

  19. Yaghi S, Bernstein RA, Passman R, Okin PM, Furie KL. Cryptogenic Stroke: Research and Practice. Circ Res. 2017;120:527-40. Doi: 10.1161/CIRCRESAHA.116.308447

  20. Arauz A, Morelos E, Colín J, Roldán J, Barboza MA. Comparison of Functional Outcome and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source (ESUS) vs. Cardioembolic Stroke Patients. PLoS ONE 11. 2016;(11):e0166091. Doi: 10.1371/journal.pone.0166091

  21. Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J, et al. Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke. 2016;47:1-14. Doi: 10.1161/STROKEAHA.116.013105.

  22. Kiyuna F, Sato N, Matsuo R, Kamouchi M, Hata J, Wakisaka Y, et al. Association of Embolic Sources with Cause-Specific Functional Outcomes Among Adults with Cryptogenic Stroke. JAMA Network Open. 2018;1(5):e182953. Doi: 10.1001/jamanetworkopen.2018.2953

  23. Coutinho JM, Derkatch S, Potvin AR, Tomlinson G, Kiehl TR, Silver FL, et al. Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke. Neurology. 2016;87:665-72.

  24. Singh N, Moody AR, Panzov V, Gladstone DJ. Carotid intraplaque hemorrhage in patients with embolic stroke of undetermined source. J Stroke Cerebrovasc Dis. 2018;27:1956-9. Doi: https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.02.042

  25. Ntaios G, Perlepe K, Sirimarco G, Strambo D, Eskandari A, Karagkiozi E, et al. Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source. Neurology. 2019;92(23):2644-52. Doi: https://doi.org/10.1212/WNL.0000000000007611

  26. Gupta A, Gialdini G, Lerario MP, Baradaran H, Giambrone A, Navi BB, et al. Magnetic Resonance Angiography Detection of Abnormal Carotid Artery Plaque in Patients With Cryptogenic Stroke. J Am Heart Assoc. 2015;4:e002012. Doi: 10.1161/JAHA.115.002012

  27. Kamel H, Gialdini G, Baradaran H, Giambrone AH, Navi BB, Lerario MP, et al. Cryptogenic Stroke and Nonstenosing Intracranial Calcified Atherosclerosis. J Stroke Cerebrovasc Dis. 2017;26(4):863-70. Doi: http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.10.035

  28. Katsanos AH, Giannopoulos S, Kosmidou M, Voumvourakis K, Parissis JT, Kyritsis AP, et al. Complex atheromatous plaques in the descending aorta and the risk of stroke: a systematic review and meta-analysis. Stroke. 2014;45:1764-70.

  29. Kamel H, Okin PM, Elkind MS, Iadecola C. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke. 2016;47:895-900. Doi: 10.1161/STROKEAHA.115.012004.

  30. Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, et al; EMBRACE Investigators and Coordinators. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370:2467-77. Doi: 10.1056/NEJMoa1311376.

  31. Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, et al; CRYSTAL AF Investigators. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478-86. Doi: 10.1056/NEJMoa1313600.

  32. Poli S, Diedler J, Härtig F, Götz N, Bauer A, Sachse T, et al. Insertable cardiac monitors after cryptogenic stroke–a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation. Eur J Neurol. 2016;23:375-81.

  33. Favilla CG, Ingala E, Jara J, Fessler E, Cucchiara B, Messé SR, et al. Predictors of Finding Occult Atrial Fibrillation After Cryptogenic Stroke. Stroke. 2015;46:1-7. Doi: 10.1161/STROKEAHA.114.007763.

  34. Yushan B, Tan BYQ, Ngiam NJ, Chan BPL, Luen TH, Sharma VK, et al. Association between Bilateral Infarcts Pattern and Detection of Occult Atrial Fibrillation in Embolic Stroke of Undetermined Source (ESUS) Patients with Insertable Cardiac Monitor. Journal of Stroke and Cerebrovascular Diseases. 2019;28(9):2448-52. Doi: https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.06.025

  35. Acampa M, Lazzerini PE, Guideri F, Tassi R, Cartocci A, Martini G. P Wave Dispersion and Silent Atrial Fibrillation in Cryptogenic Stroke: The Pathogenic Role of Inflammation. Cardiovascular & Haematological Disorders-Drug Targets. 2019;19(1):1-4. Doi: 10.2174/1871529X19666190410145501

  36. Acampa M, Lazzerini PE, Martini G. Atrial cardiopathy and sympatho-vagal imbalance in cryptogenic stroke: pathogenic mechanisms and effects on ECG markers. Front. Neurol. 2018;19(9):469. Doi: 10.3389/fneur.2018.00469

  37. Acampa M, Lazzerini PE, Guideri F, Tassi R, Lo Monaco A, Martini G. Previous use of Statins and Atrial Electrical Remodeling in Patients with Cryptogenic Stroke. Cardiovasc Hematol Disord Drug Targets. 2017;17(3):212-5.

  38. Kamel H, Okin PM, Elkind MSV, Iadecola C. Atrial Fibrillation and Mechanisms of Stroke: Time for a New Model. Stroke. 2016;47:1-5. Doi: 10.1161/STROKEAHA.115.012004.

  39. Goldberger JJ, Arora R, Green D, Greenland P, Lee DC, Lloyd-Jones DM, et al. Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the Arrhythmogenic and Thrombogenic Substrate. Circulation. 2015;132:278-91. Doi: 10.1161/CIRCULATIONAHA.115.016795

  40. Leifer D, Rundek T. Atrial cardiopathy: A new cause for stroke? Neurology. 2019;92(4). Doi: 10.1212/WNL.0000000000006749

  41. Jalini S, Rajalingam R, Nisenbaum R, Javier AD, Woo A, Pikula A. Atrial cardiopathy in patients with embolic strokes of unknown source and other stroke etiologies. Neurology. 2019;92:1-7. Doi:10.1212/WNL.0000000000006748

  42. Yaghi S, Kamel H, Elkind MSV. Atrial cardiopathy: a mechanism of cryptogenic stroke. Expert Rev Cardiovasc Ther. 2017 August;15(8):591-9. Doi: 10.1080/14779072.2017.1355238.

  43. Lattanzi S, Cagnetti C, Pulcini A, Morelli M, Maffei S, Provinciali L, et al. The P-wave terminal force in embolic strokes of undetermined source. Journal of the Neurological Sciences. 2017;375(2017):175-8. Doi: http://dx.doi.org/10.1016/j.jns.2017.01.063

  44. Kamel H, Bartz TM, Longstreth WT, Okin PM, Thacker EL, Patton KK, et al. Association Between Left Atrial Abnormality on ECG and Vascular Brain Injury on MRI in the Cardiovascular Health Study. Stroke. 2015;46:711-6. Doi: 10.1161/STROKEAHA.114.007762.

  45. Kamel H, Hunter M, Moon YP, Yaghi S, Cheung K, Di Tullio MR, et al. Electrocardiographic Left Atrial Abnormality and Risk of Stroke: Northern Manhattan Study. Stroke. 2015;46:1-4. Doi: 10.1161/STROKEAHA.115.009989.

  46. Lattanzia S, Brigo F, Cagnettia C, Di Napolid M, Silvestrinia M. Patent Foramen Ovale and Cryptogenic Stroke or Transient Ischemic Attack: To Close or Not to Close? A Systematic Review and Meta-Analysis. Cerebrovasc Dis. 2018;45:193-203. Doi: 10.1159/000488401

  47. Arboix A, Martí L, Dorison S, Sánchez MJ. Bayés syndrome and acute cardioembolic ischemic stroke. World J Clin Cases. 2017;5(3):93-101. Doi: 10.12998/wjcc.v5.i3.93

  48. Cotter PE, Martin PJ, Pugh PJ, Waburton EA, Cheriyan J, Belham M. Increased incidence of interatrial block in younger adults with cryptogenic stroke and patent foramen ovale. Cerebrovasc Dis Extra. 2001;1:36-43. Doi: 10.1159/000327346

  49. Kamel H, Longstreth WT, Tirschwell DL, Kronmal RA, Broderick JP, Palesch YY, et al. The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After cryptogenic stroke randomized trial: Rationale and methods. Int J Stroke. 2019;14(2):207-14. Doi: 10.1177/1747493018799981

  50. Amarenco P, Davis S, Jones EF, Cohen AA, Heiss WD, Kaste M, et al. Aortic Arch Related Cerebral Hazard Trial Investigators. Clopidogrel plus aspirin versus warfarin in patients with stroke and aortic arch plaques. Stroke. 2014;45:1248-57. Doi: 10.1161/STROKEAHA.113.004251.

  51. Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD, et al; NAVIGATE ESUS investigators. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378:2191-201.

  52. Diener HC, Easton JD, Granger CB, Cronin L, Duffy C, Cotton D, et al; RE-SPECT ESUS Investigators. Design of randomized, double-blind, evaluation in secondary stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with embolic stroke of undetermined source (RE-SPECT ESUS). Int J Stroke. 2015;10:1309-12.

  53. Takasugi J, Yamagami H, Noguchi T, Morita Y, Tanaka T, Okuno Y, et al. Detection of Left Ventricular Thrombus by Cardiac Magnetic Resonance in Embolic Stroke of Undetermined Source. Stroke. 2017;48:1-6. Doi: 10.1161/STROKEAHA.117.018263.

  54. Kuijpers T, Spencer FA, Siemieniuk RA, Vandvik PO, Otto CM, Lytvyn L, et al. Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline. BMJ. 2018;362:k2515. Doi: 10.1136/bmj.k2515




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