EFFECT OF THE COMBINATION OF NEUROPROTECTIVE THERAPIES ON INFARCT SIZE AND NEUROLOGICAL OUTCOME AFTER STROKE

Arnaud Potvin
Beroertes met beroerde uitkomst: is er hoop?08.54u. Er komt een oproep binnen voor de MUG. Een meisje heeft haar oma van 73 jaar aangetroffen op de grond in de gang. Wanneer de MUG ter plaatse zijn, treffen de spoedarts en verpleger een verwarde, angstige dame aan. Haar rechter lichaamshelft is verlamd en veel meer dan ja of nee kan ze niet uitspreken. In het ziekenhuis wordt een scan uitgevoerd die die vermoedelijke diagnose bevestigt: een beroerte.

EFFECT OF THE COMBINATION OF NEUROPROTECTIVE THERAPIES ON INFARCT SIZE AND NEUROLOGICAL OUTCOME AFTER STROKE

Beroertes met beroerde uitkomst: is er hoop?

08.54u. Er komt een oproep binnen voor de MUG. Een meisje heeft haar oma van 73 jaar aangetroffen op de grond in de gang. Wanneer de MUG ter plaatse zijn, treffen de spoedarts en verpleger een verwarde, angstige dame aan. Haar rechter lichaamshelft is verlamd en veel meer dan ja of nee kan ze niet uitspreken. In het ziekenhuis wordt een scan uitgevoerd die die vermoedelijke diagnose bevestigt: een beroerte. Of de dame zal overleven en in welke toestand ze zal zijn, valt nog af te wachten, maar één ding is zeker: de lijdensweg is begonnen.

Wereldwijd zijn beroertes de op één na voornaamste doodsoorzaak bij volwassenen. Wie overleeft, kampt vaak met ernstige beperkingen op korte en lange termijn, zoals verlamming, spraak- en geheugenstoornissen. In Europa zijn beroertes jaarlijks voor bijna 1,1 miljoen doden per jaar verantwoordelijk. 15% van de vrouwen en 10% van de mannen sterft ten gevolge van deze aandoening. Kortom: iedereen kent wel een slachtoffer. De uitdaging bestaat er nu in een gepast therapeutisch antwoord te vinden. Is er hoop op een doorbraak?

Hersenen in ademnood

Om een behandeling te optimaliseren of nieuwe opties te ontdekken, moeten we eerst en vooral goed begrijpen waar we mee te maken hebben. Een beroerte ontstaat meestal wanneer een bloedklonter een bloedvat afsluit en zo de bloedstroom naar de hersenen onderbreekt. In de minderheid van de gevallen gaat het om een bloeding. Onze hersenen zijn ontzettend gevoelig aan de gevolgen van zo’n onderbreking van de bloedtoevoer. Binnen de kortste keren is alle zuurstof opgebruikt en komen onze hersenen in de problemen. Een centrale groep cellen rond de afsluiting gaat onherroepelijk verloren, maar het lot van de “penumbra”, een zone rond deze kern, hangt af van wat er in de volgende uren gebeurt. Hoe langer de afsluiting, hoe erger de schade: “time is brain”. De ischemische cascade, de complexe opeenvolging van schadelijke gebeurtenissen na zuurstoftekort, is reeds grondig bestudeerd en het is duidelijk dat veel therapeutische stoffen een invloed kunnen hebben op de uitkomst na een beroerte.

rt-PA en neuroprotectie

Ondanks uitgebreid onderzoek, blijven artsen in hun therapeutisch arsenaal voorlopig ernstig beperkt. Misschien had je het zelf al bedacht: de bloedtoevoer herstellen is de belangrijkste stap in de behandeling. Dit gebeurt met rt-PA, een stof die de klonter oplost. Een groot probleem is echter dat rt-PA binnen de 4,5 uur na het begin van de beroerte moet toegediend worden om enig effect te hebben en dikwijls is niet bekend hoe lang de klonter het bloedvat afsluit. Neuroprotectie, een tweede, fundamenteel verschillende strategie houdt dan ook in de hersenen weerbaarder te maken tegen zuurstoftekort, onafhankelijk van een herstel van de bloedtoevoer. Op dit moment lijkt therapeutische hypothermie de meest beloftevolle optie binnen deze strategie. Afkoeling van het lichaam, en van de hersenen in het bijzonder, heeft een effect op een hele waaier aan stapjes in de ischemische cascade en kan dus op verschillende niveaus de uitkomst beïnvloeden.  Meerdere studies hebben het gunstige effect van hypothermie al vastgelegd, waarbij er zelfs bewezen is dat het tijdsvenster voor andere behandelingen kan verlengd worden. Deze laatste eigenschap is van ontzettend groot belang, omdat er sowieso een delay zit tussen het begin van de afsluiting, de diagnose en de behandeling. Een andere neuroprotectieve behandeling is de toediening van IGF-1, insulineachtige groeifactor-1. Deze stof grijpt ook aan op verschillende stappen in de ischemische cascade en heeft zijn nut in verscheidene dierproeven bewezen. Maar weer is de tijd een stoorfactor: enkel wanneer IGF-1 binnen het halfuur wordt toegediend, is er enige verbetering van de uitkomst te verwachten. Die 30 minuutjes zijn om voor je het weet.

Of rats and men

Een logische invalshoek voor onze studie was dan ook IGF-1 en hypothermie combineren om zo te controleren of ze samen de uitkomst na een beroerte nog beter zouden kunnen beïnvloeden dan apart en of het tijdsvenster voor IGF-1 toediening verlengd zou kunnen worden. In de naam van de wetenschap hebben we ratten een beroerte doen krijgen en ze nadien op verschillende manieren behandeld. Zo bekwamen we groepen met andere behandelingsschema’s, simpel gesteld: wel of geen hypothermie, wel of geen IGF-1 en IGF-1 op verschillende tijdstippen. We evalueerden de uitkomst op twee manieren: functioneel en histologisch. Met behulp van een serie kleine testjes keken we na hoe goed de zenuwfuncties van de ratten bewaard waren gebleven. Histologisch gingen we na hoe groot de aangetaste zone in de hersenen was door de hersenen op een speciale manier te snijden, te kleuren en met de microscoop te bekijken. Uit dit onderzoek bleek dat de ratten die behandeld werden het wel degelijk beter deden dan de ratten die niet behandeld werden en er was ook een betere uitkomst bij de combinatiebehandeling ten opzichte van de aparte behandelingen, maar jammer genoeg konden we dit niet statistisch verzilveren. Onder andere het feit dat we een onvoldoende aantal ratten hadden in elke groep vormde een belangrijke hinderpaal in het onderzoek.

Is er hoop?

Ondanks het gebrek aan een statistisch belangrijke verbetering van de uitkomst, blijven we positief. Mits uitbreiding van de groepen kunnen we in de toekomst misschien wel aantonen dat de combinatie van hypothermie en IGF-1 een goede strategie is om de gevolgen van een beroerte in te dijken. Een miraculeus wondermiddel dat al het leed na een beroerte wegneemt, zal waarschijnlijk niet snel gevonden worden. Maar als we stapje voor stapje de behandeling verfijnen, zullen vast en zeker heel wat mensen geholpen kunnen worden. 

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Universiteit of Hogeschool
Geneeskunde
Publicatiejaar
2015
Kernwoorden
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