Zusammenfassung
Bis zu 25 % aller ischämischen Schlaganfälle treten während des Schlafes auf („Wake-up
Stroke” [WUS]). Aufgrund des unklaren Zeitfensters werden diese Patienten üblicherweise
nicht in Akutstudien zur Schlaganfalltherapie eingeschlossen und auch im klinischen
Alltag erfolgt nur selten eine spezifische Therapie. Aktuell besteht keine zugelassene
Therapie für diese Patienten. Im Rahmen dieser Arbeit möchten wir einen Überblick
über die bisher zum Thema publizierte Literatur geben. Informationen zu Patientencharakteristika
und zu den derzeit verfügbaren diagnostischen und therapeutischen Möglichkeiten bei
Patienten mit WUS werden dargestellt und bewertet. Bezüglich klinischer, ätiopathologischer
und radiologischer Befunde und der Patientencharakteristika unterscheiden sich Patienten
mit WUS und solche mit bekanntem Beginn der Schlaganfallsymptome nicht wesentlich
voneinander. Auch wenn derzeit noch kein diagnostischer Goldstandard besteht, so erscheinen
moderne Bildgebungsverfahren, insbesondere die multiparametrische MRT, geeignet für
die Indikationsstellung einer Thrombolysetherapie bei WUS-Patienten. Erste Pilotstudien
zeigen, dass ein Teil dieser Patienten erfolgreich mit Thrombolyse behandelt werden
kann. Größere, prospektive, randomisierte, kontrollierte Studien müssen folgen, um
sowohl die Wirksamkeit und Sicherheit der Therapie als auch den Nutzen der modernen
Bildgebungsverfahren in dieser Patientengruppe weiter zu untersuchen. Die bisher vorliegenden
ersten Ergebnisse sollten Eingang finden in die Planung solcher zukünftigen Studien.
Abstract
Up to 25 % of all acute ischemic strokes (AIS) occur during sleep with the patients
or relatives becoming aware of their neurological deficits as they wake up. Because
of the unclear time of stroke onset patients with stroke on awakening are usually
not considered for acute therapies and excluded from most treatment trials. We give
an overview of the published data regarding ischemic wake up strokes (WUS). In particular
we focused on baseline characteristics, imaging methods and therapy strategies. Comparing
WUS patients and patients with known stroke onset there were no major differences
found regarding patient characteristics, etiology, clinical and radiological characteristics.
Even though there is no existing gold standard multiparametric neuroimaging (CT; MRI)
appears to be helpful for decision making whether to treat a WUS patient with thrombolysis
or not. Especially multiparametric MRI which proved to be safe in patients within
an extended time window might serve as an adequate diagnostic tool. The results of
first pilot studies analyzing treatment of WUS demonstrate that a substantial number
of these patients can be treated with IV thrombolysis (IVT) successfully. Large randomized,
controlled, prospective clinical trials for patients with WUS are needed to test safety
and efficacy of IVT and to evaluate the assumed benefit of multiparametric neuroimaging
techniques in this patient group. The results of first pilot studies may be instrumental
to help plan and design such trials.
Schlüsselwörter
Erwachen - ischämisch - Schlaf - Schlaganfall - MRT-basierte Thrombolyse
Key words
awakening - ischemic - sleep - stroke - MRI based thrombolysis
Literatur
1
Chaturvedi S, Adams H P, Woolson R F.
Circadian variation in ischemic stroke subtypes.
Stroke.
1999;
30
1792-1795
2
Fink J N, Kumar Jr S, Horkan C. et al .
The stroke patient who woke up: clinical and radiological features, including diffusion
and perfusion MRI.
Stroke.
2002;
33
988-993
3
Lago A, Geffner D, Tembl J. et al .
Circadian variation in acute ischemic stroke: a hospital-based study.
Stroke.
1998;
29
1873-1875
4
Serena J, Davalos A, Segura T. et al .
Stroke on awakening: looking for a more rational management.
Cerebrovasc Dis.
2003;
16
128-133
5
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.
Tissue plasminogen activator for acute ischemic stroke.
N Engl J Med.
1995;
333
1581-1587
6
Elliott W J.
Circadian variation in the timing of stroke onset: a meta-analysis.
Stroke.
1998;
29
992-996
7
Adams H P, Bendixen B H, Kappelle L J. et al .
Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter
clinical trial. TOAST. Trial of Org 10 172 in Acute Stroke Treatment.
Stroke.
1993;
24
35-41
8
Kario Jr K, Shimada K.
Change in diurnal blood pressure rhythm due to small lacunar infarct.
Lancet.
1994;
344
200
9
O’Brien E, Sheridan J, O’Malley K.
Dippers and non-dippers.
Lancet.
1988;
2
397
10
Sander D, Klingelhofer J.
Changes of circadian blood pressure patterns after hemodynamic and thromboembolic
brain infarction.
Stroke.
1994;
25
1730-1737
11
Shimada K, Kawamoto A, Matsubayashi K. et al .
Silent cerebrovascular disease in the elderly. Correlation with ambulatory pressure.
Hypertension.
1990;
16
692-699
12
Yamamoto Y, Akiguchi I, Oiwa K. et al .
Diminished nocturnal blood pressure decline and lesion site in cerebrovascular disease.
Stroke.
1995;
26
829-833
13
Kubota K, Sakurai T, Tamura J. et al .
Is the circadian change in hematocrit and blood viscosity a factor triggering cerebral
and myocardial infarction?.
Stroke.
1987;
18
812-813
14
Tofler G H, Brezinski D, Schafer A I. et al .
Concurrent morning increase in platelet aggregability and the risk of myocardial infarction
and sudden cardiac death.
N Engl J Med.
1987;
316
1514-1518
15
Andreotti F, Davies G J, Hackett D R. et al .
Major circadian fluctuations in fibrinolytic factors and possible relevance to time
of onset of myocardial infarction, sudden cardiac death and stroke.
Am J Cardiol.
1988;
62
635-637
16
Todo K, Moriwaki H, Saito K. et al .
Early CT findings in unknown-onset and wake-up strokes.
Cerebrovasc Dis.
2006;
21
367-371
17
Nadeau J O, Fang J, Kapral M K. et al .
Outcome after stroke upon awakening.
Can J Neurol Sci.
2005;
32
232-236
18
Hacke W, Kaste M, Bluhmki E. et al .
Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke.
N Engl J Med.
2008;
359
1317-1329
19
Kohrmann M, Juttler E, Fiebach J B. et al .
MRI versus CT-based thrombolysis treatment within and beyond the 3 h time window after
stroke onset: a cohort study.
Lancet Neurol.
2006;
5
661-667
20
Schellinger P D, Thomalla G, Fiehler J. et al .
MRI-based and CT-based thrombolytic therapy in acute stroke within and beyond established
time windows: an analysis of 1210 patients.
Stroke.
2007;
38
2640-2645
21
Thomalla G, Schwark C, Sobesky J. et al .
Outcome and symptomatic bleeding complications of intravenous thrombolysis within
6 hours in MRI-selected stroke patients: comparison of a German multicenter study
with the pooled data of ATLANTIS, ECASS, and NINDS tPA trials.
Stroke.
2006;
37
852-858
22
Rother J, Jonetz-Mentzel L, Fiala A. et al .
Hemodynamic assessment of acute stroke using dynamic single-slice computed tomographic
perfusion imaging.
Arch Neurol.
2000;
57
1161-1166
23
Wintermark M, Reichhart M, Cuisenaire O. et al .
Comparison of admission perfusion computed tomography and qualitative diffusion- and
perfusion-weighted magnetic resonance imaging in acute stroke patients.
Stroke.
2002;
33
2025-2031
24
Baron J C, Kummer von R, del Zoppo G J.
Treatment of acute ischemic stroke. Challenging the concept of a rigid and universal
time window.
Stroke.
1995;
26
2219-2221
25
Kaste M.
Reborn workhorse, CT, pulls the wagon toward thrombolysis beyond 3 hours.
Stroke.
2004;
35
357-359
26
Schellinger P D, Fiebach J B, Hacke W.
Imaging-based decision making in thrombolytic therapy for ischemic stroke: present
status.
Stroke.
2003;
34
575-583
27
Buckley B T, Wainwright A, Meagher T. et al .
Audit of a policy of magnetic resonance imaging with diffusion-weighted imaging as
first-line neuroimaging for in-patients with clinically suspected acute stroke.
Clin Radiol.
2003;
58
234-237
28
Schellinger P D, Jansen O, Fiebach J B. et al .
Feasibility and practicality of MR imaging of stroke in the management of hyperacute
cerebral ischemia.
Am J Neuroradiol.
2000;
21
1184-1189
29
Barber P A, Hill M D, Eliasziw M. et al .
Imaging of the brain in acute ischaemic stroke: comparison of computed tomography
and magnetic resonance diffusion-weighted imaging.
J Neurol Neurosurg Psychiatry.
2005;
76
1528-1533
30
Hand P J, Wardlaw J M, Rowat A M. et al .
Magnetic resonance brain imaging in patients with acute stroke: feasibility and patient
related difficulties.
J Neurol Neurosurg Psychiatry.
2005;
76
1525-1527
31
Kummer von R, Dzialowski I.
MRI versus CT in acute stroke.
Lancet.
2007;
369
1341-1342, author reply 1342
32
Handschu R, Garling A, Heuschmann P U. et al .
Acute stroke management in the local general hospital.
Stroke.
2001;
32
866-870
33
Hjort N, Butcher K, Davis S M. et al .
Magnetic resonance imaging criteria for thrombolysis in acute cerebral infarct.
Stroke.
2005;
36
388-397
34
Kohrmann M, Juttler E, Huttner H B. et al .
Acute stroke imaging for thrombolytic therapy – an update.
Cerebrovasc Dis.
2007;
24
161-169
35
Kidwell C S, Saver J L, Mattiello J. et al .
Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion
magnetic resonance imaging.
Ann Neurol.
2000;
47
462-469
36
Jansen O, Schellinger P, Fiebach J. et al .
Early recanalisation in acute ischaemic stroke saves tissue at risk defined by MRI.
Lancet.
1999;
353
2036-2037
37
Donnan G A, Dewey H M, Davis S M.
MRI and stroke: why has it taken so long?.
Lancet.
2007;
369
252-254
38
Fiebach J B, Schellinger P D, Jansen O. et al .
CT and diffusion-weighted MR imaging in randomized order: diffusion-weighted imaging
results in higher accuracy and lower interrater variability in the diagnosis of hyperacute
ischemic stroke.
Stroke.
2002;
33
2206-2210
39
Chalela J A, Kidwell C S, Nentwich L M. et al .
Magnetic resonance imaging and computed tomography in emergency assessment of patients
with suspected acute stroke: a prospective comparison.
Lancet.
2007;
369
293-298
40
Kidwell C S, Chalela J A, Saver J L. et al .
Comparison of MRI and CT for detection of acute intracerebral hemorrhage.
JAMA.
2004;
292
1823-1830
41
Kang D W, Chalela J A, Dunn W. et al .
MRI screening before standard tissue plasminogen activator therapy is feasible and
safe.
Stroke.
2005;
36
1939-1943
42
Schellinger P D, Warach S.
Therapeutic time window of thrombolytic therapy following stroke.
Curr Atheroscler Rep.
2004;
6
288-294
43
Hellier K D, Hampton J L, Guadagno J V. et al .
Perfusion CT helps decision making for thrombolysis when there is no clear time of
onset.
J Neurol Neurosurg Psychiatry.
2006;
77
417-419
44
Iosif C, Oppenheim C, Trystram D. et al .
MR Imaging-Based Decision in Thrombolytic Therapy for Stroke on Awakening: Report
of 2 Cases.
AJNR Am J Neuroradiol.
2008;
29
1314-1316
45
Adams H P, Effron M B, Torner Jr J. et al .
Emergency administration of abciximab for treatment of patients with acute ischemic
stroke: results of an international phase III trial: Abciximab in Emergency Treatment
of Stroke Trial (AbESTT-II).
Stroke.
2008;
39
87-99
46
Cho A H, Sohn S I, Han M K. et al .
Safety and efficacy of MRI-based thrombolysis in unclear-onset stroke. A preliminary
report.
Cerebrovasc Dis.
2008;
25
572-579
47
Breuer L, Schellinger P D, Huttner H B. et al .
Feasibility and safety of MRI-based thrombolysis in patients with stroke on awakening
– initial single center experience.
Int J Stroke.
2010;
5
in press
48
Barreto A D, Martin-Schild S, Hallevi H. et al .
Thrombolytic Therapy for Patients Who Wake-Up With Stroke.
Stroke.
2009;
40
827-832
49
The IMS Study Investigators. Combined intravenous and intra-arterial recanalization
for acute ischemic stroke: the Interventional Management of Stroke Study.
Stroke.
2004;
35
904-911
50
Albers G W, Bates V E, Clark W M. et al .
Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard
Treatment with Alteplase to Reverse Stroke (STARS) study.
JAMA.
2000;
283
1145-1150
51
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
2003-2011
52
Hill M D, Buchan A M.
Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke
Effectiveness Study.
CMAJ.
2005;
172
1307-1312
53
Lewandowski C A, Frankel M, Tomsick T A. et al .
Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute
ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial.
Stroke.
1999;
30
2598-2605
Dr. Lorenz Breuer
Universitätsklinikum Erlangen Neurologische Klinik
Schwabachanlage 6
91054 Erlangen
Email: Lorenz.Breuer@uk-erlangen.de