Bedeutung der Perfusions-Computertomographie beim akuten ischämischen Insult [Elektronische Ressource] / vorgelegt von Jite Erharhaghen

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Aus dem Zentrum für Neurologie Neurologische Klinik und Hertie-Institut für klinische Hirnforschung Abteilung Allgemeine Neurologie Komm. Ärztlicher Direktor: Professor Dr. A. Melms Bedeutung der Perfusions-Computertomographie beim akuten ischämischen Insult Inaugural-Dissertation zur Erlangung des Doktorgrades der Medizin der Medizinischen Fakultät der Eberhard Karls Universität zu Tübingen vorgelegt von Jite Erharhaghen aus Kokori-Inland, Nigeria 2009 1 Dekan: Professor Dr. I. B. Autenrieth 1. Berichterstatter: Professor Dr. A. Luft 2. Berichterstatter: Professor Dr. Dipl.-Phys. T. Nägele 2 Contents !"#$%%&'($##"') *****************************************************************************************************+ ,-#./$0.*********************************************************************************************************************1 2'./34"0.53 '***************6 ,5%73(7.85#7#."49******************************************************************************************************:: ;$.&/5$<#7=7;&.834#*******************************:> !"#$%&'()*+,-----------------------------------------------------------------------------------------------------------------------------------------------------------./ 0121'&1'324*2)245&'&----------------.6 ?&#"<.
Publié le : jeudi 1 janvier 2009
Lecture(s) : 99
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Source : TOBIAS-LIB.UB.UNI-TUEBINGEN.DE/VOLLTEXTE/2009/3912/PDF/WERTIGKEIT_DER_PERFUSION_CT_A5.PDF
Nombre de pages : 36
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Aus dem Zentrum für Neurologie
Neurologische Klinik und Hertie-Institut für klinische Hirnforschung
Abteilung Allgemeine Neurologie
Komm. Ärztlicher Direktor: Professor Dr. A. Melms

Bedeutung der Perfusions-Computertomographie
beim akuten ischämischen Insult

Inaugural-Dissertation
zur Erlangung des Doktorgrades
der Medizin

der Medizinischen Fakultät
der Eberhard Karls Universität
zu Tübingen

vorgelegt von
Jite Erharhaghen
aus
Kokori-Inland, Nigeria
2009
1
Dekan: Professor Dr. I. B. Autenrieth

1. Berichterstatter: Professor Dr. A. Luft
2. Berichterstatter: Professor Dr. Dipl.-Phys. T. Nägele
2 Contents
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3 !"#$%%&'($##"')7
Hintergrund. Der ischämische Insult ist ein Notfall, der nach wie vor mit sehr
hoher Morbidität und Mortalität verbunden ist. Intravenöse und intraarterielle
Thrombolyse innerhalb eines Zeitfensters von 4,5 bzw. 6 h ist effektiv, sicher und
gilt inzwischen als Standardtherapie. Vor einer Lyse muss die intrazerebrale
Blutung als wichtigste Differentialdiagnose des ischämischen Insults mittels
Computertomographie (CT) oder Kernspintomographie (MRT) ausgeschlossen
werden.
Die CT-Agiographie und Perfusions-CT-Bildgebung (PCT) ist eine schnell
verfügbare und Zusatzuntersuchung, die über den Ausschluss einer Blutung
hinaus den Positivnachweis einer Ischämie erbringen kann.
Ziel. Ziel unsere retrospektive Studie war es, den prädiktiven Wert der PCT für
Infarktgröße, initiales Defizit, frühe Besserung und Prognose bei lysierten und
nicht lysierten Patienten zu überprüfen.
Methoden. Bei 92 Patienten (47 lysiert), die bei Aufnahme eine CT mit PCT
sowie eine Kontroll-Bildgebung nach 24 Stunden erhalten hatten, wurden
verschiedene PCT-Parameter gemessen und deren Vorhersagewert auf die
initiale Symptomatik (gemessen mit dem NIHSS) und ihre Verbesserung, auf die
Infarktgröße und der Grad der Behinderung nach der Entlassung aus der
Rehabiliation (gemessen mittels modified Rankin Scale) ermittelt.
Ergebnisse. Je größer die Fläche der Perfusionsdefizits und je älter der Patient,
desto schwerer war die neurologische Symptomatik bei Aufnahme (NIHSS). Die
endgültige Infarktgröße wird ebenfalls von der Fläche des Perfusionsdefizits
bestimmt und ist zudem größer, je verzögerter der Kontrastmittelbolus im
Ischämieareal ankommt (time-to-peak Latenz). Während kein Parameter die
frühzeitige Verbesserung der neurologischen Symptomatik vorhersagen konnte,
korrelierte der Grad der Behinderung nach Entlassung aus der Rehabilitation mit
der Fläche des Perfusionsdefizits – dies allerdings nur in der nicht-lysierten
Gruppe.
4 Schlußfolgerung. Die PCT Bildgebung korreliert mit dem akuten Defizit und hat
einen Vorhersagewert für die Größe der endgültigen Läsion und das funktionelle
Outcome. PCT stellt eine medizinisch sinnvolle Zusatzuntersuchung beim
akuten ischämischen Insult da, die in Routineprotokolle aufgenommen werden
sollte, weil mit ihr der Positivnachweis einer zerebralen Ischämie mit
Vorhersagewert erbracht werden kann. Diese Studie erlaubt keine
Schlussfolgerungen in Bezug auf die Kernspintomographie bei akuten
Schlaganfall, die im Vergleich zum CT die überlegene Methode sein könnte.

Schlüsselwörter: Ischämische Schlaganfall, Perfusions-CT, TTP, CBV, CBF,
Penumbra, Entgültige Inafrktgröße, functionelle Outcome.

5 ,-#./$0.7
Introduction. Ischemic stroke is a medical emergency that is still associated
with high morbidity and mortality. Intravenous or intraarterial thrombolysis is an
effective treatment to improve stroke outcomes when applied within 4.5 to 6
hours after symptom onset. Before thrombolysis an intracerebral hemorrhage
has to be ruled out by computed tomography (CT) or magnetic resonance
imaging (MRI).
CT angiography (CTA) and perfusion CT (PCT) are additional CT-based
methods, that are readily available and allow for a direct demonstration of acute
ischemia.
Aim. The aim of this retrospective study was to evaluating the predictive value of
PCT for infarct volume, initial stroke-related deficit, and early improvement and
mid-term outcomes after stroke in patients receiving thrombolysis and those that
did not.
Methods. 92 subjects (47 received thrombolysis) with ischemic stroke who
underwent non-enhanced CT and PCT on admission and a non-enhanced CT
after 24 hours were included. PCT parameters were measured and their
predictive value for stroke volume, initial deficit, early improvement, and outcome
were evaluated.
Results. The larger the perfusion deficit and the older the patient, the graver
was the stroke-related deficit upon admission (NIHSS). Likewise, final stroke
volume depended on the size of the perfusion deficit. Additionally, later arrival of
contrast in the ischemic area (time-to-peak latency) predicted stroke volume.
While no parameter explained the variability in early improvement, the outcome
after rehabilitation was in part explained by the size of the initial perfusion deficit
– however, only in patients not receiving thrombolysis.
Conclusion. PCT imaging provides parameters that are correlated with the
acute deficit and predict final lesion size and functional outcome. PCT represents
a useful exam that should be added to the diagnostic CT work-up for acute
6 ischemic stroke, because it provides direct evidence of ischemia that can be
used for the determination of prognosis. This study does not allow for
conclusions about MRI in the acute setting, which may still be the superior
method when compared with CT.

Key Words: Ischemic stroke, perfusion CT, TTP, CBV, CBF, Penumbra, final
infarct size, functional outcome.

7 2'./34"0.53'7
1Ischemic stroke is an emergency . The incidence in industrialised countries is
approximately 150 cases per 100,000 per year. Hence, ischemic stroke is a
common disease. Stroke is more prevalent in higher age groups. Consequently,
stroke is the third leading cause of death and the leading cause of disability
among adults in the Western world. Two thirds of all patients with ischemic
stroke are either dead or dependent after 6 months. Stroke survivors are at risk
2, 3of recurrent stroke .
In selected patients, intravenous administration of recombinant tissue-type
plasminogen activator (rTPA) within 4.5 h or its intraarterial administration within
6h of symptom onset (thrombolysis), is an effective treatment option that
4-8improves outcomes . Thrombolysis can only be given when a hemorrhagic
stroke is ruled out by cranial imaging studies. These can be computed
tomography (CT) or magnetic resonance imaging (MRI). While non-contrast
enhanced CT (NECT) rules out hemorrhage, MRI can additionally demonstrate
early ischemia. NECT is typically normal during the first hours of an ischemic
stroke and even if early signs of ischemia are observed, regional definition of
ischemic tissue and differentiation between viable and irreversibly damaged
9brain is not possible . Measuring brain perfusion with contrast-enhanced CT may
substantially improve the CT-based diagnosis of acute ischemic stroke.
Under normal circumstances cerebral perfusion is held constant by the
autoregulation of cerebral arteries. The normal cerebral blood flow (CBF) in the
10grey substance varies between 50 and 60 ml/100g of brain tissue/min . When a
cerebral artery is occluded, tissue survival depends on the effectiveness of
collateral blood supply, e.g., through the circle of Willis or leptomeningeal
anastomoses. Cellular protein synthesis ceases at blood flows below 35 ml/100
g/min. At CBF levels lower than 20 ml/100 g/min synaptic transmission ceases
(loss of function). Both cellular deficits are usually reversible if blood flow is
reinstated (recanalisation/reperfusion). Further decrease of cerebral blood flow
11, 12below 10 ml/100 g/min leads to irreversible cell damage (loss of viability) .
8 The perfusion “window” in which cells are still viable, but their electrical function
is lost and causes neurological symptoms, opens a window for treatments that
13aim at recanalization .
A cerebral infarct usually has a core in which perfusion is reduced below the
viability threshold. In the border zone to the adjacent normal tissue, collaterals
can still provide sufficient perfusion to preserve viability, but not function. This
border zone is called “penumbra”. It is conceptualized that recanalization through
thrombolysis saves the penumbra thereby reducing final infarct size and
14 6, 7neurological deficits .
The benefit of thrombolysis has been shown to vanish, when used later than 4.5
hours of symptom onset. With time tissue dies and the likelihood of hemorrhagic
complications of thrombolysis increases. Within this time window, thrombolysis is
the more effective the earlier it is administered. Therefore, patients have to be
diagnosed and treated as rapidly as possible (“Time is Brain”). Acute stroke
imaging protocols have to compromise between loss of time and gain of
6, 15-18information .
Perfusion CT (PCT) is a relatively new technique that measures perfusion by
tracking a bolus of contrast medium passing through cerebral arteries and brain
tissue. Areas of reduced perfusion can be identified and the degree of reduction
can be quantified. Quantification uses deconvolution of the arterial and tissue
enhancement curves, which is a mathematical operation allowing for the
calculation of mean transit time (MTT) or time-to-peak (TTP) of the contrast
enhancement. Regional cerebral blood volume (rCBV) can be derived as the
area under the curve (AUC). Regional cerebral blood flow (rCBF) is instead
19derived from the central blood volume equation (CBF = CBV/MTT) .
PCT provides excellent information regarding the severity and extent of
ischemia. The use of various perfusion maps helps to differentiate the core of
20infarction from the ischemic penumbra zone – that is, viable tissue with
19, 21, 22reduced perfusion that potentially can be salvaged by thrombolysis .
CBF (cerebral blood flow) and CBV (cerebral blood volume) have some value in
23, 24assessing the viability of ischemic brain tissue in humans . The reliability and
9 reproducibility of perfusion parameter measurements provided by CT have been
20, 23-26validated in the literature . Sparacia et al (2007) showed that the mean
transit time (MTT) is the perfusion parameter best suited for discriminating
between viable and infarcted tissue.
In a CT Perfusion study combined with ASPECT score (Alberta Stroke Program
Early Computed Tomography) assessing the extent of the ischemic lesion, a
cerebral blood volume (CBV) ASPECT score was a good predictor of clinical
outcome after intravenous thrombolysis (odds ratio, 31.43; 95% confidence
interval, 3.41-289.58; p<0.002), and was superior to NIHSS, NECT and CT
27angiography (CTA) . Examination time for the entire acute stroke imaging
protocol (NECT, CTA and CTP) does not exceed 5 to 6 minutes for the CT scans
and another 5 to 8 minutes for standardized analysis of the CTP and CTA
28studies .
Information on the predictive value of CTP parameters on the final stroke volume
and clinical outcome in thrombolyzed and non-thrombolyzed patients is limited.
In Tübingen, NECT, CTA and PCT are routinely performed in every patient with
a presumed stroke or transient ischemic attack. This large collection of cases
has been retrospectively analysed to evaluate the predictive value of CTP
parameters.
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