Kryptogener ischämischer Schlaganfall: Zeit für einen Paradigmenwechsel in Diagnose und Therapie?

Zusammenfassung

Ein kryptogener ischämischer Schlaganfall wird nach den TOAST-Kriterien angenommen wenn andere Ursachen wie eine kardiale Emboliequelle, eine Makroangiopathie, ein lakunärer Infarkt oder eine andere Schlaganfallätiologie nicht nachgewiesen werden konnten. Während für die meisten definierten Schlaganfallätiologien mittlerweile gezielt Sekundärpräventionsstudien durchgeführt wurden, bestand bisher bei Patienten mit kryptogenem Schlaganfall das Problem, dass diese Ätiologie bisher nicht ausreichend operational definiert ist. Das neue Konzept des „Embolic Stroke of Undetermined Source“ (ESUS) umfasst eine operationale Definition anhand der bildgebenden Diagnostik mit Ausschluss von lakunären Infarkten. Außerdem müssen durch Ultraschall, CTA oder MRA hämodynamisch relevante Stenosen der hirnversorgenden Gefäße im Gefäßgebiet des aktuellen Infarkts ausgeschlossen werden. Die minimale kardiale Diagnostik zum Ausschluss von Vorhofflimmern ist ein 24-Stunden-Holter-Monitoring. Da die meisten Schlaganfälle, welche die ESUS-Kriterien erfüllen, wahrscheinlich embolischer Natur sind, ist eine randomisierte Sekundärpräventionsstudie mit neuen oralen Antikoagulanzien versus Thrombozytenfunktionshemmern gerechtfertigt.

Abstract

According to the TOAST criteria, an ischemic stroke is defined as cryptogenic when common causes like cardioembolism, large artery atherosclerosis, small vessel disease or other defined etiologies can be excluded. While several stroke prevention trials have investigated well-defined stroke etiologies, cryptogenic stroke so far was insufficiently defined. The new definition of “Embolic Stroke of Undetermined Source (ESUS)” is based on the exclusion of lacunar infarction by brain imaging and of relevant stenosis of vessels supplying the affected brain territory by ultrasound, CT- or MR-angiography. Cardiac workup must include ECG Holter monitoring for 24 hours to rule out atrial fibrillation. Because the majority of strokes meeting the ESUS criteria are of (cardio-)embolic origin, a randomized secondary prevention trial investigating new oral anticoagulants versus antiplatelet therapy is warranted.

Schlüsselwörter

ischämischer Schlaganfall - TOAST-Kriterien - Makroangiopathie - lakunärer Infarkt - kardiogene Embolie

Keywords

ischemic stroke - TOAST criteria - large artery atherosclerosis - lacunar infarction - cardioembolism

• Literatur

• 1 Adams Jr HP, Bendixen BH, Kappelle LJ 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
• 2 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: 440-445
• 3 Alsheikh-Ali AA, Thaler DE, Kent DM. Patent foramen ovale in cryptogenic stroke: incidental or pathogenic?. Stroke 2009; 40: 2349-2355
• 4 Overell JR, Bone I, Lees KR. Interatrial septal abnormalities and stroke: a meta-analysis of case-control studies. Neurology 2000; 55: 1172-1179
• 5 Davis D, Gregson J, Willeit P. Patent foramen ovale, ischemic stroke and migraine: systematic review and stratified meta-analysis of association studies. Neuroepidemiology 2013; 40: 56-67
• 6 Handke M, Harloff A, Olschewski M et al. Patent foramen ovale and cryptogenic stroke in older patients. N Engl J Med 2007; 357: 2262-2268
• 7 Weimar C, Holle DN, Benemann J et al. Current management and risk of recurrent stroke in cerebrovascular patients with right-to-left cardiac shunt. Cerebrovasc Dis 2009; 28: 349-356
• 8 Carroll JD, Saver JL, Thaler DE et al. Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 2013; 368: 1092-1100
• 9 Meier B, Kalesan B, Mattle HP et al. Percutaneous closure of patent foramen ovale in cryptogenic embolism. N Engl J Med 2013; 368: 1083-1091
• 10 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: 991-999
• 11 Russo C, Jin Z, Rundek T. Atherosclerotic disease of the proximal aorta and the risk of vascular events in a population-based cohort: the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. Stroke 2009; 40: 2313-2318
• 12 Di Tullio MR, Russo C, Jin Z et al. Aortic arch plaques and risk of recurrent stroke and death. Circulation 2009; 119: 2376-2382
• 13 Meissner I, Khandheria BK, Sheps SG et al. Atherosclerosis of the aorta: risk factor, risk marker, or innocent bystander? A prospective population-based transesophageal echocardiography study. J Am Coll Cardiol 2004; 44: 1018-1024
• 14 Capmany RP, Ibanez MO, Pesquer XJ. Complex atheromatosis of the aortic arch in cerebral infarction. Current cardiology reviews 2010; 6: 184-193
• 15 Tunick PA, Nayar AC, Goodkin GM et al. Effect of treatment on the incidence of stroke and other emboli in 519 patients with severe thoracic aortic plaque. Am J Cardiol 2002; 90: 1320-1325
• 16 Timsit SG, Sacco RL, Mohr JP et al. Brain infarction severity differs according to cardiac or arterial embolic source. Neurology 1993; 439: 728-733
• 17 Nakamura T, Tsutsumi Y, Shimizu Y et al. Ulcerated carotid plaques with ultrasonic echolucency are causatively associated with thromboembolic cerebrovascular events. J Stroke Cerebrovasc Dis 2013; 22: 93-99
• 18 Freilinger TM, Schindler A, Schmidt C et al. Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke. JACC Cardiovascular imaging 2012; 5: 397-405
• 19 Seet RC, Friedman PA, Rabinstein AA. Prolonged rhythm monitoring for the detection of occult paroxysmal atrial fibrillation in ischemic stroke of unknown cause. Circulation 2011; 124: 477-486
• 20 Flint AC, Banki NM, Ren X et al. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke: The stroke and monitoring for PAF in real time (SMART) registry. Stroke 2012; 43: 2788-2790
• 21 Rizos T, Guntner 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: 2689-2694
• 22 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
• 23 Stahrenberg R, Weber-Kruger 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: 2884-2888
• 24 Ziegler PD, Glotzer TV, Daoud EG et al. Incidence of newly detected atrial arrhythmias via implantable devices in patients with a history of thromboembolic events. Stroke 2010; 41: 256-260
• 25 Cotter PE, Martin PJ, Ring L et al. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology 2013; 80: 1546-1550
• 26 Fisher CM. Lacunar strokes and infarcts: a review. Neurology 1982; 32: 871-876
• 27 Gorter JW, Algra A, van Gijn J et al. SPIRIT: predictors of anticoagulant-related bleeding complications in patients after cerebral ischemia. Cerebrovasc Dis 1997; 7 (Suppl. 04) 3258
• 28 The ESPRIT Study Group. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet Neurol 2007; 6: 115-124
• 29 Benavente OR, Hart RG, McClure LA et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med 2012; 367: 817-825
• 30 Grond M, Jauss M, Hamann G et al. Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke. Stroke 2013;
• 31 European Stroke Organisation (ESO) Executive Committee and ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457-507
• 32 Endres M, Diener H, Röther J. Sekundärprävention des Schlaganfalls. In: Diener HC, Weimar C, Kommission Leitlinien der Deutschen Gesellschaft für Neurologie, Hrsg. Leitlinien für Diagnostik und Therapie in der Neurologie. 5.. Auflage. Stuttgart: Thieme; 2012
• 33 Meschia JF, Barrett KM, Chukwudelunzu F et al. Interobserver agreement in the trial of org 10172 in acute stroke treatment classification of stroke based on retrospective medical record review. J Stroke Cerebrovasc Dis 2006; 15: 266-272
• 34 Mohr JP, Thompson JL, Lazar RM et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001; 345: 1444-1451
• 35 Weber R, Goertler M, Benemann J et al. Prognosis after cryptogenic cerebral ischemia in patients with coagulopathies. Cerebrovasc Dis 2009; 28: 611-617
• 36 Serena J, Marti-Fabregas J, Santamarina E et al. Recurrent stroke and massive right-to-left shunt: results from the prospective Spanish multicenter (CODICIA) study. Stroke 2008; 39: 3131-3136
• 37 Petty GW, Brown RD, Whisnant JP et al. Ischemic stroke subtypes. A population-based study functional outcome, survival and recurrence. Stroke 2000; 31: 1062-1068
• 38 Kolominsky-Rabas PL, Weber M, Gefeller O et al. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke 2001; 32: 2735-2740
• 39 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: 1740-1746
• 40 Connolly SJ, Eikelboom J, Joyner C et al. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364: 806-817
• 41 Diener HC, Eikelboom J, Connolly SJ et al. Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial. Lancet Neurol 2012; 11: 225-231