The twilight of cryptogenic ischaemic stroke – cardio-embolism is the most frequent cause

Authors: D. Šaňák 1;  M. Hutyra 2;  M. Král 1;  M. Špaček 2;  A. Bártková 1
Authors place of work: Komplexní cerebrovaskulární centrum, Neurologická klinika LF UP a FN Olomouc 1;  Komplexní kardiovaskulární centrum, I. interní klinika – kardiologická LF UP a FN Olomouc 2
Published in the journal: Cesk Slov Neurol N 2018; 81(3): 290-297
Category: Přehledný referát
doi: 10.14735/amcsnn2018290


Early and accurate identification of the cause of ischaemic stroke (IS) is essential for an effective and safe secondary prevention. Etiological classification systems are used to establish an optimal diagnostic management to identify the cause of IS. However, the TOAST classification is still mostly used, but the newer ASCOD system is more detailed and accurate. If the cause of IS remains unclear or is not being identified, it is classified as cryptogenic IS. About 25–30% of all IS are cryptogenic and in the population of young patients under 50 years of age, the rate of cryptogenic IS exceeds 50% of all IS. Recently published data and clinical experience show an increasing rate of cardio-embolization, which is now presented as a cause of IS in up to 45–50% of all cases and it is considered the most frequent cause of cryptogenic IS. Higher frequency of cardio-embolization is based on more accurate and extensive diagnostics focused on the detection of relevant structural or functional heart abnormities associated with risk of embolization. Atrial fibrillation (AF) is the most frequent cause of cardio-embolization. Implementation of 24h ECG-Holter monitoring in the clinical routine and using long-term ECG-Holter monitoring or implantation of a subcutaneous cardiac monitor led to increased detection of paroxysmal AF in patients with cryptogenic IS. Transesophageal echocardiography (TEE) allows reliable detection of structural heart abnormities and other rare causes of IS. An assessment of specific serum cardiac markers can also helpful; elevated values may be associated with presence of relevant heart abnormities. Currently, a comprehensive cardiologic examination should be a standard part of routine diagnostic management in most IS patients; moreover, in cryptogenic IS patients it should include TEE and long-term ECG-Holter monitoring in case of negative 24h monitoring.

Key words:
ischaemic stroke – cardio-embolization – cryptogenic – atrial fibrillation – ECG-Holter – echocardiography

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


1. Tomek A, Bar M, Mikulík R et al. The impact of nationwide centrally organized stroke care system on recanalization rates: Czech Republic experience [abstract]. Eur Stroke J 2017; 2(1): 59. Available from URL: http:/ / doi/ pdf/ 10.1177/ 2396987 317705236.

2. Adams HP, Bendixen BH, Kappel le LJ et al. Classification of subtype of acute ischemic stroke definitions for use in a multicenter clinical trial. Stroke 1993; 24(1): 35–41.

3. Han SW, Kim SH, Lee JY et al. A new subtype classification of ischemic stroke based on treatment and etiologic. Eur Neurol 2007; 57(2): 96–102. doi: 10.1159/ 000098059.

4. Amarenco P, Bogousslavsky J, Caplan LR et al.The ASCOD phenotyping of ischemic stroke (up­-dated ASCO phenotyping). Cerebrovasc Dis 2013; 36(1): 1–5. doi: 10.1159/  000352050.

5. Amarenco P, Bogousslavsky J, Caplan LR et al. New approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis 2009; 27(5): 502–508. doi: 10.1159/  000210433.

6. Hart RG, Diener HC, Coutts SB et al. Embolic strokesof undetermined source: the case for a new clinicalconstruct. Lancet Neurol 2014; 13(4): 429–438. doi: 10.1016/ S1474-4422(13)70310-7.

7. Amarenco P. Cryptogenic stroke, aortic arch atheroma, patent foramen ovale, and the risk of stroke. Cerebrovasc Dis 2005; 20 (Suppl 2): 68–74. doi: 10.1159/ 000089358.

8. Bang OY, Lee PH, Joo JS et al. Frequency and mechanisms of stroke recurrence after cryptogenic stroke. Ann Neurol 2003; 54(2): 227–234. doi: 10.1002/ ana.10644.

9. Cerrato P, Grasso M, Imperiale D et al. Stroke in young patients: etiopathogenesis and risk factors in different age classes. Cerebrovasc Dis 2004; 18(2): 154–159. doi: 10.1159/ 000079735.

10. Putaala J, Metso AJ, Metso TM et al. Analysis of 1008 consecutive patients aged 15 to 49 with first-ever ischemic stroke: the Helsinki young stroke registry. Stroke 2009; 40(4): 1195–1203. doi: 10.1161/ STROKEAHA.108.529883.

11. Putaala J, Haapaniemi E, Metso AJ et al. Recurrent ischemic events in young adults after first-ever ischemic stroke. Ann Neurol 2010; 68(5): 661–671. doi: 10.1002/ ana.22091.

12. Stahrenberg R, Weber-Krüger M, Seegers J et al. Enhanced detection of paroxysmal atrial fibrillation by early and prolonged continuous Holter monitoring in patients with cerebral ischemia presenting in sinus rhythm. Stroke 2010; 41(12): 2884–2888. doi: 10.1161/ STROKEAHA.110.591958.

13. Wachter R, Weber-Krüger M, Seegers J et al. Age-dependent yield of screening for undetected atrial fibrillation in stroke patients: the Find-AF study. J Neurol 2013; 260(8): 2042–2045. doi: 10.1007/ s00415-013-6935-x.

14. Friberg L, Rosenqvist M, Lindgren A et al. High prevalence of atrial fibrillation among patients with ischemic stroke. Stroke 2014; 45(9): 2599–2605. doi: 10.1161/ STROKEAHA.114.006070.

15. Fauchier L, Clementy N, Pelade C et al. Patients with ischemic stroke and incident atrial fibrillation: a nation­wide cohort study. Stroke 2015; 46(9): 2432–2437. doi: 10.1161/ STROKEAHA.115.010270.

16. Perera KS, Vanassche T, Bosch J et al. Global survey of the frequency of atrial fibrillation-associated stroke. Stroke 2016; 47(9): 2197–2202. doi: 10.1161/ STROKEAHA.116.013378.

17. Král M, Šaňák D, Školoudík D et al. Kardioembolizace je nejčastější příčinou akutní ischemické cévní mozkové příhody u pacientů přijatých do komplexního cerebrovaskulárního centra do 12 hodin od začátku příznaků –výsledky studie HISTORY. Cesk Slov Neurol N 2016; 79/ 112(1): 61–67. doi: 10.14735/ amcsnn201661.

18. Go AS, Mozzaffarian D, Roger VL et al. Heart dis­-ease and stroke statistics: 2014 update: a report from the American Heart Association. Circulation 2014; 129(3): e28–e292. doi: 10.1161/ 01.cir.0000441139.02102.80.

19. Gladstone DJ, Spring M, Dorian P et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 2014; 370(26): 2467–2477. doi: 10.1056/ NEJMoa1311376.

20. Sanna T, Diener HC, Passman RS et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014; 370(26): 2478–2486. doi: 10.1056/ NEJMoa1313600.

21. Hart RG, Catanese L, Perera KS et al. Embolic stroke of undetermined source: a systematic review and clin­ical update. Stroke 2017; 48(4): 867–872. doi: 10.1161/ STROKEAHA.116.016414.

22. Ntaios G, Papavasileiou V, Milionis H et al. Embolic strokes of undetermined source in the Athens stroke reg­istry: a descriptive analysis. Stroke 2015; 46(1): 176–181. doi: 10.1161/ STROKEAHA.114.007240.

23. Ntaios G, Papavasileiou V, Lip GYH et al. embolic stroke of undetermined source and detection of atrial fibrillation on follow-up: how much causality is there? J Stroke Cerebrovasc Dis 2016; 25(12): 2975–2980. doi: 10.1016/ j.jstrokecerebrovasdis.2016.08.015.

24. Wang Y, Wang Y, Zhao X et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013; 369(1): 11–19. doi: 10.1056/ NEJMoa1215340.

25. Johnston SC, Amarenco P, Albers GW et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med 2016; 375(1): 35–43. doi: 10.1056/ NEJMoa1603060.

26. Meissner I, Khandheria BK, Heit JA et al. Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study. J Am Coll Cardiol 2006; 47(2): 440–445. doi: 10.1016/ j.jacc.2005.10.044.

27. Mas JL, Arquizan C, Lamy C et al, and the Patent Foramen Ovale and Atrial Septal Aneurysm Study Group. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001; 345(24): 1740–1746. doi: 10.1056/ NEJMoa011503.

28. Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 2000; 55(8): 1172–1179.

29. Gu X, He Y, Li Z et al. Comparison of frequencies of patent foramen ovale and thoracic aortic atherosclerosis in patients with cryptogenic ischemic stroke undergoing transesophageal echocardiography. Am J Cardiol 2011; 108(12): 1815–1819. doi: 10.1016/ j.amjcard.2011.07.058.

30. Handke M, Harloff A, Olschewski M et al. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007; 357(22): 2262–2268. doi: 10.1056/ NEJMoa071422.

31. Potpara TS, Lip GY. Ischemic stroke and atrial fibrillation – a deadly serious combination. Cerebrovasc Dis 2011; 32(5): 461–462. doi: 10.1159/ 000332030.

32. Wolf PA. Awareness of the role of atrial fibrillation as a cause of ischemic stroke. Stroke 2014; 45(2): e19–e21. doi: 10.1161/ STROKEAHA.113.003282.

33. Zoni-Berisso M, Lercari F, Carraza T et al. Epidemiology of atrial fibrillation: European perspective. Clin Epidemiol 2014; 6: 213–220. doi: 10.2147/ CLEP.S47385.

34. Hart RG, Pearce LA, Rothbart RM et al. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibril­lation Investigators. J Am Coll Cardiol 2000; 35(1): 183–187.

35. Kerr CR, Humphries KH, Talajic M et al. Progression to chronic atrial fibrillation after the initial dia­gnosis of paroxysmal atrial fibril¬lation: result from the Canadian Registry of Atrial Fibrillation. Am Heart J 2005; 149(3): 489–496. doi: 10.1016/ j.ahj.2004.09.053.

36. Stoddard MF, Dawkins PR, Prince CR et al. Left atrial appendage thrombus is not uncommon in patients with acute atrial fibrillation and a recent embolic event: a transesophageal echocardiographic study. J Am CollCardiol 1995; 25(2): 452–459.

37. Manning WJ, Silverman DI, Waksmonski CA et al. Prevalence of residual left atrial thrombi among patients with acute thromboembolism and newly recognized atrial fibrillation. Arch Intern Med 1995; 155(20): 2193–2198.

38. Fuster V, Ryden LE, Cannom DS et al. ACC/ AHA/ ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114(7): 257–354. doi: 10.1161/ CIRCULATIONAHA.106.177292.

39. Kirchhof P, Auricchio A, Bax J et al. Outcome parameters for trials in atrial fibrillation: recommendations from a consensus conference organized by the German Atrial Fibrillation Competence Network and the European Heart Rhythm Association. Europace 2007; 9(11): 1006–1023. doi: 10.1093/ europace/ eum191.

40. Tayal AH, Tian M, Kelly KM et al. Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke. Neurology 2008; 71: 1696–1701.

41. Ziegler PD, Rogers JD, Ferreira SW et al. real-world experience with insertable cardiac monitors to find atrial fibrillation in cryptogenic stroke. Cerebrovasc Dis 2015; 40(3–4): 175–181. doi: 10.1159/ 000439063.

42. Rizos T, Güntner J, Jenetzky E et al. Continuous stroke unit electrocardiographic monitoring versus 24-hour Holter electrocardiography for detection of paroxysmal atrial fibrillation after stroke. Stroke 2012; 43(10): 2689–2694. doi: 10.1161/ STROKEAHA.112.654954.

43. Grond M, Jauss M, Hamann G et al. Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study. Stroke 2013; 44(12): 3357–3364. doi: 10.1161/ STROKEAHA.113.001884.

44. Šaňák D, Hutyra M, Král M, HISTORY study group. Poruchy srdečního rytmu u mladých pacientů s kryptogenní ischemickou cévní mozkovou příhodou. Cesk Slov Neurol N 2015; 78/111(6): 669–674.

45. Benjamin EJ, Levy D, Vaziri SM et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 1994; 271: 840–844.

46. Krahn AD, Manfreda J, Tate RB et al. The natural history of atrial fibrillation: incidence, risk factors, and prog­nosis in the Manitoba Follow-Up Study. Am J Med 1995; 98(5): 476–484. doi: 10.1016/ S0002-9343(99)80348-9.

47. Psaty BM, Manolio TA, Kuller LH et al. Incidence of and risk factors for atrial fibrillation in older adults. Circulation 1997; 96(7): 2455–2461.

48. Anegawa T, Kai H, Adachi H et al. High-sensitive troponin T is associated with atrial fibrillation in a general population. Int J Cardiol 2012; 156(1): 98–100. doi: 10.1016/ j.ijcard.2011.12.117.

49. Patton KK, Heckbert SR, Alonso A et al. N-terminal pro-B-type natriuretic peptide as a predictor of incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis: the effects of age, sex and ethnicity. Heart 2013; 99(24): 1832–1836. doi: 10.1136/ heartjnl-2013-304724.

50. Král M, Šaňák D, Veverka T et al. Troponin T in acute ischemic stroke. Am J Cardiol 2013; 112(1): 117–121. doi: 10.1016/ j.amjcard.2013.02.067.

51. Král M, Šaňák D, Veverka T et al. Troponin T: correlation with location and volume of acute brain infarction. Int J Cardiol 2015; 181: 127–132. doi: 10.1016/ j.ijcard.2014.12.027.

52. Favilla CG, Ingala E, Jara J et al. Predictors of finding occult atrial fibrillation after cryptogenic stroke. Stroke 2015; 46(5): 1210–1215. doi: 10.1161/ STROKEAHA.114.007763.

53. Binici Z, Intzilakis T, Nielsen OW et al. Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke. Circulation 2010; 121(17): 1904–1911. doi: 10.1161/  CIRCULATIONAHA.109.874982.

54. Chong BH, Pong V, Lam KF et al. Frequent premature atrial complexes predict new occurrence of atrial fibrillation and adverse cardiovascular events. Europace 2012; 14(7): 942–947. doi: 10.1093/ europace/ eur389.

55. Kochhäuser S, Dechering DG, Dittrich R et al. Supraventricular premature beats and short atrial runs predict atrial fibrillation in continuously monitored patients with cryptogenic stroke. Stroke 2014; 45(3): 884–886. doi: 10.1161/ STROKEAHA.113.003788.

56. Gladstone DJ, Dorian P, Spring M et al. Atrial premature beats predict atrial fibrillation in cryptogenic stroke. Stroke 2015; 46(4): 936–941. doi: 10.1161/ STROKEAHA.115.008714.

57. Tsang TS, Barnes ME, Bailey KR et al. Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women. Mayo Clin Proc 2001; 76(5): 467–475. doi: 10.4065/ 76.5.467.

58. Fatema K, Barnes ME, Bailey KR et al. Minimum vs. maximum left atrial volume for prediction of first atrial fibrillation or flutter in an elderly cohort: a prospective study. Eur J Echocardiogr 2009; 10(2): 282–286. doi: 10.1093/ ejechocard/ jen235.

59. Miller DJ, Khan MA, Schultz LR et al. Outpatient cardiac telemetry detects a high rate of atrial fibrillation in cryptogenic stroke. J Neurol Sci 2013; 324(1–2): 57–61. doi: 10.1016/ j.jns.2012.10.001.

60. Cotter PE, Martin PJ, Ring L et al. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology 2013; 80(17): 1546–1550. doi: 10.1212/ WNL.0b013e31828f1828.

61. Gaillard N, Deltour S, Vilotijevic B et al. Detection of paroxysmal atrial fibrillation with transtelephonic ECG in TIA or stroke patients. Neurology 2010; 74: 1666–1670. doi: 10.1212/ WNL.0b013e3181e0427e.

62. Park H, Shin J, Ban JE et al. Left atrial appendage: Morphology and function in patients with paroxysmal and persistent atrial fibrillation. Int J Cardiovasc Imaging 2013; 29(4): 935–944. doi: 10.1007/ s10554-012-0161-y.

63. Hunter RJ, Liu Y, Lu Y et al. Left atrial wall stress distribution and its relationship to electrophysiologic remodel­ing in persistent atrial fibrillation. Circ Arrhythm Electrophysiol 2012; 5(2): 351–360. doi: 10.1161/ CIRCEP.111.965541.

64. Korhonen M, Muuronen A, Arponen O et al. Left atrial appendage morphology in patients with suspect­ed cardiogenic stroke without known atrial fibrillation. PLoS ONE 2015; 10(3): e0118822. doi: 10.1371/ journal.pone.0118822.

65. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996; 61(2): 755–759. doi: 10.1016/ 0003-4975(95)00887-X.

66. Yasuda R, Murata M, Roberts R et al. Left atrial strain is a powerful predictor of atrial fibrillation recurrence after catheter ablation: study of a heterogeneous population with sinus rhythm or atrial fibrillation. Eur Heart J Cardiovasc Imaging 2015; 16(9): 1008–1014. doi: 10.1093/ ehjci/ jev028.

67. Daccarett M, Badger TJ, Akoum N et al. Association of left atrial fibrosis detected by delayed-enhancement magnetic resonance imaging and the risk of stroke in patients with atrial fibrillation. J Am Coll Cardiol 2011; 57(7): 831–838. doi: 10.1016/ j.jacc.2010.09.049.

68. Windecker S, Stortecky S, Meier B. Paradoxical embolism. J Am Coll Cardiol 2014; 64(4): 403–415. doi: 10.1016/ j.jacc.2014.04.063.

69. Kent DM, Ruthazer R, Weimar C et al. An index to identify stroke-related vs. incidental patent foramen ovale in cryptogenic stroke. Neurology 2013; 81(7): 619–625. doi: 10.1212/ WNL.0b013e3182a08d59.

70. Meissner I, Whisnant JP, Khandheria BK et al. Prevalence of potential risk factors for stroke assessed by trans­-esophageal echocardiography and carotid ultrasonography: the SPARC study. Stroke Prevention: Assessment of Risk in a Community. Mayo Clin Proc 1999; 74(9): 862–869.

71. Schneider B, Harath P, Vogel P et al. Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. J Am Coll Cardiol 1990; 16(4): 1000–1009.

72. Mas JL, Arquizan C, Lamy C et al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm, or both. N Engl J Med 2001; 345(24): 1740–1746. doi: 10.1056/ NEJMoa011503.

73. Clergeau MR, Hamon M, Morello R et al. Silent cerebral infarcts in patients with pulmonary embolism and a patent foramen ovale: a prospective diffusion-weighted MRI study. Stroke 2009; 40(12): 3758–3762. doi: 10.1161/ STROKEAHA.109.559898.

74. Konstantinides SV, Torbicki A, Agnelli G et al. 2014 ESC guidelines on the dia­gnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35(43): 3033–3069. doi: 10.1093/ eurheartj/ ehu283.

75. Furlan AJ, Reisman M, Massaro J et al. Closure or medical therapy for cryptogenic stroke with patent foramen ovale. N Engl J Med 2012; 366(11): 991–999. doi: 10.1056/ NEJMoa1009639.

76. Meier B, Kalesan B, Mattle HP et al. for the PC TrialInvestigators. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013; 368(12): 1083–1091. doi: 10.1056/ NEJMoa1211716.

77. Carroll JD, Saver JL, Thaler DE et al. for the RESPECT Investigators: Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013; 368(12): 1092–1100. doi: 10.1056/ NEJMoa1301440.

78. Wolfrum M, Froehlich GM, Knapp G et al. Stroke prevention by percutaneous closure of patent foramen ovale: a systematic review and meta-analysis. Heart 2014; 100(5): 389–395. doi: 10.1136/ heartjnl-2013-304394.

79. Kernan WN, Ovbiagele B, Black HR et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke 2014; 45(7): 2160–2236. doi: 10.1161/ STR.0000000000000024.

80. Diener HC, Easton JD, Granger CB et al. 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(8): 1309–1312. doi: 10.1111/ ijs.12630.

81. U.S. National Library of Medicine. Rivaroxaban versus aspirin in secondary prevention of stroke and prevention of systemic embolism in patients with recent embolic stroke of undetermined source (ESUS). [online]. Available from URL: https:/ / show/ NCT02313909.

82. Geisler T, Poli S, Meisner C et al. Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): rationale and study design. Int J Stroke 2017; 12(9): 985–990. doi: 10.1177/ 1747493016681019.

83. Reddy VY, Doshi SK, Sievert H et al. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT AF (watchman left atrial appendage system for embolic protection in patients with atrial fibrillation) trial. Circulation 2013; 127(6): 720–729. doi: 10.1161/ CIRCULATIONAHA.112.114389.

84. Holmes DR, Kar S, Price MJ et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014; 64(1): 1–12. doi: 10.1016/ j.jacc.2014.04.029.

85. Kirchhof P, Benussi S, Kotecha D et al. 2016 ESC Guide­lines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37(38): 2893–2962. doi: 10.1093/ eurheartj/ ehw210.

Dětská neurologie Neurochirurgie Neurologie

Článek vyšel v časopise

Česká a slovenská neurologie a neurochirurgie

Číslo 3

2018 Číslo 3

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…

Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se