Rekanalisierende Behandlung des akuten Schlaganfalls

Zusammenfassung

Die systemische Thrombolyse der akuten zerebralen Ischämie mit rt-PA im 3-Stunden-Zeitfenster entwickelte sich in den vergangenen Jahren zur Standardtherapie. Seit Ende 2002 besteht eine europaweite Zulassung für diese Indikation. Für das 3- bis 6-Stunden-Zeitfenster gibt es bislang noch keine allgemein akzeptierte Behandlungsstrategie. Die Datenlage ist am günstigsten für die intraarterielle Thrombolyse, vorausgesetzt es liegt ein proximaler Verschluss der Arteria cerebri media vor. Eine systemische Thrombolyse jenseits der ersten 3 Stunden wird nicht generell empfohlen, aber in einzelnen Zentren bei ausgewählten Patienten durchgeführt. Neben Thrombolyseverfahren im engeren Sinne und neuen Ansätzen zur Optimierung thrombolytischer Therapie (z. B. Patientenauswahl mittels MRT) werden einzelne neuroradiologisch-interventionelle und chirurgische Rekanalisierungsmethoden diskutiert.

Summary

Systemic thrombolysis with rt-PA within 3 hours after symptom onset has developed into a standard therapy for acute stroke patients. Recombinant t-PA is now licensed in Europe for this indication. Within 3 to 6 hours, no general therapeutic standard has been established yet. Currently, the available data are in favor of intra-arterial thrombolysis for patients with proximal occlusions of the middle cerebral artery. Systemic thrombolysis is not generally recommended in this time window, but is used in some centers for selected patients. In addition to thrombolysis and new strategies to improve thrombolysis (including patient selection with MRI), several interventional and surgical recanalization techniques are discussed.

Schlüsselwörter

Schlaganfall - Thrombolyse - Rekanalisation

Keywords

Stroke - thrombolysis - recanalization

• Literatur

• 1 Stroke trials directory. 2003 Internet stroke center. at www.Strokecenter.Org/trials/
• 2 Albers GW. Expanding the window for thrombolytic therapy in acute stroke: The potential role of acute MRI for patient selection. Stroke 1999; 30: 2230-7.
• 3 Alexandrov AV, Demchuk AM, Felberg RA. et al. High rate of complete recanalization and dramatic clinical recovery during t-PA infusion when continuously monitored with 2-MHz transcranial doppler monitoring. Stroke 2000; 31: 610-4.
• 4 Arnold M, Schroth G, Nedeltchev K. et al. Intra-arterial thrombolysis in 100 patients with acute stroke due to middle cerebral artery occlusion. Stroke 2002; 33: 1828-33.
• 5 Astrup J, Siesjö BK, Symon L. Thresholds in cerebral ischemia – the ischemic penumbra. Stroke 1981; 12: 723-5.
• 6 Barber PA, Davis SM, Darby DG. et al. Absent middle cerebral artery flow predicts the presence and evolution of the ischemic penumbra. Neurology 1999; 52: 1125-32.
• 7 Baron JC. Mapping the ischaemic penumbra with pet: Implications for acute stroke treatment. Cerebrovasc Dis 1999; 9: 193-201.
• 8 Baron JC. Perfusion thresholds in human cerebral ischemia: Historical perspective and therapeutic implications. Cerebrovasc Dis 2001; 11 (Suppl. 01) 2-8.
• 9 Behrens S, Daffertshofer M, Spiegel D. et al. Low-frequency, low-intensity ultrasound accelerates thrombolysis through the skull. Ultra Med Biol 1999; 25: 269-73.
• 10 Brandt T, von Kummer R, Muller-Kuppers M. et al. Thrombolytic therapy of acute basilar artery occlusion. Variables affecting recanalization and outcome. Stroke 1996; 27: 875-81.
• 11 Clark WM, Wissman S, Albers GW. et al. Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The Atlantis Study: A randomized controlled trial. Alteplase thrombolysis for acute noninterventional therapy in ischemic stroke. JAMA 1999; 282: 2019-26.
• 12 Daffertshofer M, Fatar M. Therapeutic ultrasound in ischemic stroke treatment: Experimental evidence. Eur J Ultra 2002; 16: 121-30.
• 13 del Zoppo GJ, Higashida RT, Furlan AJ. et al. Proact: A phase ii randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Proact investigators. Prolyse in acute cerebral thromboembolism. Stroke 1998; 29: 4-11.
• 14 Eckert B, Koch C, Thomalla G. et al. Acute basilar artery occlusion treated with combined intravenous abciximab and intra-arterial tissue plasminogen activator: Report of 3 cases. Stroke 2002; 33: 1424-7.
• 15 Ernst R, Pancioli A, Tomsick T. et al. Combined intravenous and intra-arterial recombinant tissue plasminogen activator in acute ischemic stroke. Stroke 2000; 31: 2552-7.
• 16 Furlan A, Higashida R, Wechsler L. et al. Intra-arterial prourokinase for acute ischemic stroke. The Proact II Study: A randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA 1999; 282: 2003-11.
• 17 Gerriets T, Postert T, Goertler M. et al. Duplexsonographic assessment of the cerebrovascular status in acute stroke. A useful tool for future stroke trials. Stroke 2000; 31: 2342-5.
• 18 Hacke W, Kaste M, Fieschi C. et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274: 1017-25.
• 19 Hacke W, Kaste M, Fieschi C. et al. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian acute stroke study investigators. Lancet 1998; 352: 1245-51.
• 20 Hacke W, Brott T, Caplan L. et al. Thrombolysis in acute ischemic stroke: Controlled trials and clinical experience. Neurology 1999; 53: S3-14.
• 21 Heiss WD, Graf R, Wienhard K. et al. Dynamic penumbra demonstrated by sequential multi-tracer PET after middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab 1994; 14: 892-902.
• 22 Heiss WD. Ischemic penumbra: Evidence from functional imaging in man. J Cereb Blood Flow Metab 2000; 20: 1276-93.
• 23 Hossmann K-A. Viability thresholds and the penumbra of focal ischemia. Ann Neurol 1994; 36: 557-65.
• 24 Huber R, Muller BT, Seitz RJ. et al. Carotid surgery in acute symptomatic patients. Eur J Vasc Endovasc Surg 2003; 25: 60-7.
• 25 Kidwell CS, Saver JL, Mattiello J. et al. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging. Ann Neurol 2000; 47: 462-9.
• 26 Kolominsky-Rabas P, Heuschmann PU. Epidemiologie des Schlaganfalls. In: Hamann G, Siebler M, von Scheidt W. (Hrsg). Schlaganfall: Klinik, Diagnostik, Therapie. Interdisziplinäres Handbuch. Landsberg: Ecomed; 2002: 25-45.
• 27 Lee DH, Jo KD, Kim HG. et al. Local intraarterial urokinase thrombolysis of acute ischemic stroke with or without intravenous abciximab: A pilot study. J Vasc Interv Radiol 2002; 13: 769-74.
• 28 Lewandowski CA, Frankel M, Tomsick TA. et al. Combined intravenous and intra-arterial rt-PA versus intra-arterial therapy of acute ischemic stroke: Emergency management of stroke (EMS) bridging trial. Stroke 1999; 30: 2598-605.
• 29 Liberatore GT, Samson A, Bladin C. et al. Vampire bat salivary plasminogen activator (desmoteplase): A unique fibrinolytic enzyme that does not promote neurodegeneration. Stroke 2003; 34: 537-43.
• 30 Lindsberg PJ, Kaste M. Thrombolysis for acute stroke. Curr Opin Neurol 2003; 16: 73-80.
• 31 Lutsep HL. Mechanical thrombolysis. at www.Emedicine.Com/neuro/topic702.Htm#section~author_information.2002
• 32 Marchal G, Beaudouin V, Rioux P. et al. Prolonged persistence of substantial volumes of potentially viable brain tissue after stroke: A correlative PET-CT study with voxel-based data analysis. Stroke 1996; 27: 599-606.
• 33 Mayer TE, Hamann GF, Brueckmann HJ. Treatment of basilar artery embolism with a mechanical extraction device: Necessity of flow reversal. Stroke 2002; 33: 2232-5.
• 34 Morris DC, Zhang L, Zhang ZG. et al. Extension of the therapeutic window for recombinant tissue plasminogen activator with argatroban in a rat model of embolic stroke. Stroke 2001; 32: 2635-40.
• 35 Müller B, Sandmann W. Karotis-Frühop. In: Hamann G, Siebler M, von Scheidt W. (Hrsg). Schlaganfall: Klinik, Diagnostik, Therapie. Interdisziplinäres Handbuch. Landsberg: Ecomed; 2002: 463-71.
• 36 Neumann-Haefelin T, Wittsack HJ, Wenserski F. et al. Diffusion- and perfusion-weighted MRI: The dwi/pwi mismatch region in acute stroke. Stroke 1999; 30: 1591-7.
• 37 Neumann-Haefelin T, Moseley ME, Albers GW. New magnetic resonance imaging methods for cerebrovascular disease: Emerging clinical applications. Ann Neurol 2000; 47: 559-70.
• 38 Oppenheim C, Stanescu R, Dormont D. et al. False-negative diffusion-weighted MR findings in acute ischemic stroke. Am J Neuroradiol 2000; 21: 1434-40.
• 39 Ringleb PA, Schellinger PD, Schranz C. et al. Thrombolytic therapy within 3 to 6 hours after onset of ischemic stroke: Useful or harmful?. Stroke 2002; 33: 1437-41.
• 40 Rother J, Schellinger PD, Gass A. et al. Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours. Stroke 2002; 33: 2438-45.
• 41 Spreer J, Els T, Hetzel A. et al. Primary stenting as emergency therapy in acute basilar artery occlusion. Neuroradiology 2002; 44: 791-5.
• 42 Tanne D, Kasner SE, Demchuk AM. et al. Markers of increased risk of intracerebral haemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: The multi-center rt-PA stroke survey. Circulation 2002; 105: 1679-85.
• 43 The NINDS-Stroke-Study-Group. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA stroke trial. Stroke 1997; 28: 2119-25.
• 44 The-NINDS-t-PA-Stroke-Study-Group. Tissue plasminogen activator for acute ischemic stroke. The national institute of neurological disorders and stroke rt-PA stroke study group. N Engl J Med 1995; 333: 1581-7.
• 45 The-NINDS-t-PA-Stroke-Study-Group. Intracerebral haemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA stroke study group. Stroke 1997; 28: 2109-18.
• 46 Wardlaw JM, del Zoppo G, Yamaguchi T. Thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2000; 2: CD000213.
• 47 Wintermark M, Bogousslavsky J. Imaging of acute ischemic brain injury: The return of computed tomography. Curr Opin Neurol 2003; 16: 59-63.
• 48 Zeumer H, Freitag HJ, Zanella F. et al. Local intra-arterial fibrinolytic therapy in patients with stroke: Urokinase versus recombinant tissue plasminogen activator (rt-PA). Neuroradiology 1993; 35: 159-62.