Diagnostische biomerkers voor een ischemische beroerte: een meta-analyse

Thomas Monbailliu Joline Goossens
Onderzoek naar biomerkers om de diagnose van een ischemische beroerte te kunnen stellen.

Time is brain

Time is brain

We hadden de ganse dag geholpen in het huis van onze dochter en toen ik ‘s avonds naar het toilet ging voelde ik mij niet goed worden: ik had helemaal geen hoofdpijn, voelde geen pijn maar ik viel wel op de grond. Ik wist niet wat er gebeurde: ineens kon ik niet meer spreken en was mijn rechter lichaamshelft verlamd. Ik kon niet meer goed bewegen en alleen maar wachten tot mijn man me kwam zoeken. Hij had al eens geroepen, maar ik kon niet antwoorden...”.

Wereldwijd zijn beroertes de op één na voornaamste doodsoorzaak bij volwassenen. In Europa alleen al zijn beroertes verantwoordelijk voor 1.1 miljoen doden per jaar. Een op de zeven vrouwen en een op de tien mannen sterven ten gevolge van de aandoening.
Wie wel overleefd heeft vaak te kampen met jarenlange revalidatie en met ernstige blijvende beperkingen zoals verlammingen, spraak- en geheugenstoornissen.

Wat is een beroerte nu juist?
Een beroerte ontstaat in de meerderheid van de gevallen wanneer een bloedklonter een bloedvat afsluit en zo de bloedstroom naar (een deel van) de hersenen onderbreekt. In de minderheid van de gevallen ontstaat een beroerte door een bloeding van de bloedvaten die de hersenen van bloed voorzien.

Onze hersenen zijn enorm afhankelijk van de stoffen (glucose, zuurstof) die ze via het bloed ontvangen. Een onderbreking van de bloedtoevoer zal dus onmiddellijke gevolgen hebben voor het hersenweefsel. Een centrale groep cellen die zich rond de onderbreking van het bloedvat bevinden sterven binnen de kortste keren af door een gebrek aan zuurstof. Hun functie gaat daarna onherroepelijk verloren. De zone (“de penumbra”) rondom deze centrale kern valt echter nog te redden indien er vroegtijdig wordt ingegrepen. Hoe langer de afsluiting duurt, hoe meer cellen van deze zone zullen sterven en hoe groter de schade wordt. Met andere woorden: ‘Time is brain’.

Hoe kan men proberen om nog zoveel mogelijk hersenweefsel te sparen?
Misschien had je het antwoord op deze vraag zelf al bedacht: men kan zoveel mogelijk hersenweefsel sparen door de bloedtoevoer naar dit hersenweefsel opnieuw te herstellen.
De enige mogelijkheid waarover we nu beschikken om dit te doen is recombinant tissue plasminogen activator (rtPA). rtPA is een stof die de bloedklonter doet oplossen en zo de bloedtoevoer naar de hersenen herstelt. Het grote probleem is echter dat rtPA binnen de 4,5 uur na het begin van de beroerte moet toegediend worden om enig effect te hebben.

Tijd is cruciaal
Zoals u wellicht al kon afleiden is tijd een cruciale factor bij een ischemische beroerte.  Het is dan ook van levensbelang om de diagnose van een ischemische beroerte zo snel mogelijk te stellen. Er zijn een aantal ziektes (‘stroke mimics’) die klinisch zeer sterk lijken op een ischemische beroerte. Op basis van de kliniek is het dus niet mogelijk om de diagnose van een ischemische beroerte met 100% zekerheid te stellen. Er is bijkomend beeldvorming nodig, zoals een CT-scan van de hersenen. Op deze beeldvorming is een ischemische beroerte in de acute fase echter niet goed zichtbaar. Beeldvorming wordt dus voornamelijk gebruikt om andere ziektes die een beroerte kunnen nabootsen en wel goed zichtbaar zijn op een CT-scan (hersenbloeding, hersentumor) uit te sluiten. Op dit moment zijn de kliniek en de beeldvorming de gouden standaard om de diagnose van een ischemische beroerte te stellen.

Maar zoals u wellicht ondertussen al aanvoelt, is het niet altijd evident om in de acute fase een ischemische beroerte te onderscheiden van ziektes die een beroerte kunnen nabootsen. Deze diagnostische onzekerheid bij patiënten met symptomen van een beroerte is dan ook één van de grootste redenen waardoor rtPA niet binnen de 4,5 uur kan toegediend worden.

Biomerkers
Een aanpak die hierin zou kunnen helpen is het gebruik van biomerkers. Biomerkers zijn bepaalde stoffen in het lichaam (zoals eiwitten) die de toestand van een ziekte weergeven. Zo vindt tijdens een beroerte een ischemische cascade plaats. Dit is een complexe opeenvolging van schadelijke gebeurtenissen ten gevolge van het zuurstof tekort. Tijdens deze cascade komen verschillende stoffen (biomerkers) vrij in het bloed. Deze biomerkers kunnen gemeten en gekwantificeerd worden en geven de staat van de ziekte aan. Door deze biomarkers te meten in het bloed is het dus mogelijk zijn om patiënten met een ischemische beroerte te onderscheiden van gezonde personen of patiënten met een andere aandoening. In ons onderzoek hebben we dan ook onderzocht welke biomerkers hiertoe in staat waren. Van de zesentwintig onderzochte biomerkers waren er twee (BNP en S100B) in staat om patiënten met een ischemische beroerte significant te onderscheiden van gezonde personen en/of patiënten met een andere aandoening.

Door het bepalen van de concentratie van deze twee biomerkers in een diagnostische test kan men dus de diagnose van een ischemische beroerte sneller en accurater stellen dan het op dit moment mogelijk is op basis van de kliniek en beeldvorming. Op deze manier zullen meer patiënten rtPA krijgen binnen het gepaste therapeutische venster en zullen er uiteindelijk minder patiënten overlijden of moeten leven met ernstige beperkingen, want onthoud: ‘Time is brain’…

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Universiteit of Hogeschool
Master Geneeskunde
Publicatiejaar
2016
Promotor(en)
Prof. Dr. S. Idrissi
Kernwoorden
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