UvA-DARE (Digital Academic Repository) Subarachnoid hemorrhage: Early evaluation and optimization of management Germans, M.R. Publication date 2015 Document Version Final published version Link to publication Citation for published version (APA): Germans, M. R. (2015). Subarachnoid hemorrhage: Early evaluation and optimization of management. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:06 Oct 2021 d i e o g d n n s a a n h a h n c f o m i r o r t t a e a n n r u G o r e l i . o t a m a R a v e z e i o g b m n y a m l i n n r e t u e a a p M h m o S E Subarachnoid hemorrhage: early evaluation and optimization of management Menno R. Germans 31452 Germans.qxp_cover 07-01-15 14:04 Pagina 1 Subarachnoid hemorrhage Early evaluation and optimization of management Menno Robbert Germans © 2015 M.R. Germans, Amsterdam, the Netherlands ISBN: 978-90-6464-845-8 Funding: ABN-AMRO, Covidien, Promedics Medical Systems BV, Stichting ter Bevordering van Neurochirurgische Ontwikkeling, Zeiss Cover design and layout: Ferdinand van Nispen tot Pannerden, Citroenvlinder DTP & Vormgeving, Bilthoven, The Netherlands Printing: GVO drukkers en vormgevers, Ede, The Netherlands Subarachnoid hemorrhage Early evaluation and optimization of management ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. D.C. van den Boom ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op woensdag 4 maart 2015, te 14.00 uur door Menno Robbert Germans geboren te Geleen Promotiecommissie Promotor: prof. dr. W.P. Vandertop prof. dr. G.J.E. Rinkel Co-promotor: dr. D. Verbaan dr. B.A. Coert Overige leden: prof. dr. R.J. de Haan prof. dr. M.B. Vroom prof. dr. C.B.L.M. Majoie prof. dr. C.M.F. Dirven dr. A. van der Zwan Faculteit der Geneeskunde Subarachnoid hemorrhage: early evaluation and optimization of management Contents Chapter 1 General introduction and outline 9 Part 1 Early rebleed risk and reduction of rebleeds 23 Chapter 2 Time intervals from subarachnoid hemorrhage to 25 rebleed Journal of Neurology 2014;261(7): 1425-1431 Chapter 3 Time intervals from aneurysmal subarachnoid 41 hemorrhage to treatment and factors contributing to delay Journal of Neurology 2014;261(3): 473-479 Chapter 4 Antifibrinolytic therapy for aneurysmal subarachnoid 57 haemorrhage (review) (Adapted from) Cochrane Database of Systematic Reviews 2013;8: CD001245 Chapter 5 Ultra-early tranexamic acid after subarachnoid 109 hemorrhage (ULTRA): study protocol for a randomized controlled trial Trials 2013;14: 143 Part 2 Evaluation of the spinal axis in non-aneurysmal 121 subarachnoid hemorrhage Chapter 6 Spinal vascular malformations in non-perimesencephalic 123 subarachnoid hemorrhage Journal of Neurology 2008;255(12): 1910-1915 Chapter 7 Spinal axis imaging in non-aneurysmal subarachnoid 137 hemorrhage: a prospective cohort study Journal of Neurology 2014;261(11): 2199-2203 Chapter 8 Yield of spinal imaging in non-aneurysmal, non- 149 perimesencephalic subarachnoid hemorrhage Neurology; accepted for publication Chapter 9 General discussion and future considerations 157 Chapter 10 Summary 171 Chapter 11 Samenvatting 179 List of abbreviations 186 List of publications 187 Dankwoord 189 Curriculum vitae 191 Chapter 1 General introduction and outline Chapter 1 GENERAL INTRODUCTION Introduction A subarachnoid hemorrhage (SAH) is a life-threatening disease that was first described in the 18th century, but it took until the early 20th century until the term “spontaneous subarachnoid hemorrhage” was introduced by the English neurologist Sir Charles P. Symonds1. Nowadays, the term spontaneous SAH describes the presence of blood in the subarachnoid space that is not the result of a trauma. In approximately 85% of cases a SAH is caused by a rupture of an aneurysm on one of the intracranial arteries and this is called an aneurysmal SAH (aSAH)2. Because the intracranial arteries lie within the subarachnoid space, where also the cerebrospinal fluid (CSF) is located, the blood is able to spread over the complete brain and spinal cord. This blood can mostly be visualized on a plain computed tomography (CT-) scan of the brain or, when the amount of blood is too small or the blood has been washed out in time, it can be diagnosed by a lumbar puncture (LP) or magnetic resonance (MR-) scan2-6. A SAH is considered a medical emergency due to the severity of the hemorrhage and the high risk of early complications, which is reflected in the high mortality of approximately 40% and significant neurological and cognitive deficits in the majority of the survivors 7-9. A CT-scan of the brain is made as soon as possible to confirm the diagnosis and patients are admitted to specialized SAH treatment centers. The purpose is to treat the aneurysm as early as feasible, and at least within the first 72 hours, according to the most recent guidelines6, 10. The most severe complication that is prevented by early diagnosis and aneurysm treatment is a recurrent hemorrhage, which is associated with an even worse outcome than a single hemorrhage6, 10-13. In 15% of all SAH patients no aneurysm is visualized on initial vascular imaging investigations, which classifies these patients into the group of non-aneurysmal SAH2. About two-thirds of these hemorrhages are a perimesencephalic hemorrhage (PMSAH), first described by van Gijn et al in 1985, and this reflects a separate type of hemorrhage with a more favorable course of the disease14. Its exact pathogenic mechanism is unknown but ruptures of small angiomas, capillary teleangiectasias or aneurysms of perforating arteries have been 10 General introduction and outline discussed as possible explanations, and also atypical venous drainage patterns or intramural hematomas of the basilar artery have been seen in this type of hemorrhage15-17. Moreover, some case reports mention a spinal vascular 1 malformation causing a PMSAH18, 19. The remaining non-aneurysmal patients, those who do not have a PMSAH, have a non-perimesencephalic SAH (NPSAH)6. In some of these patients an aneurysm is found on repeat investigations and those are finally also classified as an aSAH. Almost half of the NPSAH patients develop similar complications as in aSAH20, 21. This indicates that this type of hemorrhage resembles an aSAH more than a PMSAH. A search for every possible cause in NPSAH patients seems warranted to prevent potential complications and to inform patients properly about the course of their disease. This might also include a search for a spinal origin, which can not only cause a recurrent hemorrhage, but also slowly progressive spinal cord deficits over months to years22. Aneurysmal SAH Aneurysm after second investigation NPSAH Non-­‐aneurysmal SAH PMSAH Overview of classification of patients with spontaneous subarachnoid hemorrhage after first vascular imaging investigaton (SAH = subarachnoid hemorrhage; NPSAH = non-perimesencephalic SAH with first negative digital subtraction angiography; PMSAH = perimesencephalic SAH). See text for explanation. 11 Chapter 1 Epidemiology Aneurysmal subarachnoid hemorrhage The incidence of aneurysmal rupture is approximately 9 per 100.000 persons per year, although in some countries, such as Finland and Japan, the incidence is higher23-25. It comprises only 5% of stroke in the complete population, but due to the high morbidity and mortality in the relatively young population (average age at onset is 50 years), the impact on the socioeconomic and health-care system is high2, 9, 23, 26. The prevalence of an intracranial aneurysm is between 3 and 5%27, 28, but the risk that it ruptures is only 1.1-1.4% per year29, 30, leading to a lifetime risk between 0.02% and 7.2%31. Some known risk factors for growth and rupture of aneurysms are female gender, age, hypertension, history of SAH, aneurysm size and location, smoking and excessive alcohol intake10, 29. In 3-7% of SAH patients no hemorrhage is seen on the CT-scan despite clinical suspicion of SAH. This is probably a consequence of a small amount of blood in the CSF or a long interval since the hemorrhage2, 32. These patients are diagnosed afterwards by LP and approximately 45% of them appear to have an intracranial aneurysm32, 33. Non-aneurysmal subarachnoid hemorrhage Patients with PMSAH encompass 10% of all spontaneous SAH, with a reported incidence of 0.5 per 100.000 persons per year34. These patients are significantly younger and less likely to be women. Because of the much more favorable course of the disease, the impact on the socioeconomic and health-care system is much lower. When there is no evidence for intracranial vascular pathology in a SAH that has been proven by either an aneurysmal hemorrhage pattern on CT or a negative CT with positive LP, the patient is categorized into NPSAH.