De evidentie rond het coiling-clipping paradigma in de behandeling van cerebrale aneurysmata uitdagen en in kaart brengen door middel van multimodale stratificatie.

Cerebral aneurysms (CA) are caused by local microscopic alterations in the wall of intracranial arteries, leading to macroscopic deformities of these blood vessels. Saccular aneurysms represent the most frequent subtype of CA, which often have a berry-like configuration, residing on the bifurcation of intracranial arteries. Alternate, rarer, presentation forms include fusiform aneurysms, which consist of a circumferential expansion of the afflicted vessel, mycotic aneurysms, which result from infectious emboli causing damage to the vessel wall and finally blister-aneurysms represented small CA with only a ‘pseudowall’ of thin adventitia and fibrous organization of a former blood cloth. Saccular aneurysms occur in 1-3% of the population in autopsy and imaging studies, whereas fusiform aneurysms account for 3-13% of all aneurysms (1, 2). The cerebral vasculature can be divided into the anterior circulation which arises through the carotid arteries and the posterior circulation, which is fed by both vertebral arteries. CA most often occur in the anterior circulation around the circle of Willis (80-85%), mainly at the origin of the posterior communicating artery, anterior communicating artery and the bi/trifurcation of the middle cerebral artery (3). In the posterior circulation, the most common sites are the basilar artery bifurcation and the junction between the vertebral artery and the posterior inferior cerebellar artery (4).  The most dreaded consequence of a CA is a rupture, which causes a subarachnoid hemorrhage (SAH), which only stops when a thrombus is formed at the rupture site. This catastrophic occurrence is fatal in 26-50% of patients, where 10-15% die at home or during transport to the hospital (5, 6). Only 55% of patients remain independent after a SAH and 19% stay dependent (6). The patients who do stay independent frequently have deficits in their cognitive functions, decision-making capability and have a decreased quality-of-life (7). After an aneurysmal rupture, there is a considerable risk of re-bleeding, estimated to be 3-4% the first 24 hours and afterwards 1-2% re-bleeding rate each day of the following month (8). Re-bleeding is even more lethal than the initial rupture, where it poses a mortality rate of 70% (9). Treatment of a ruptured CA can be either through an endovascular approach, or surgically clipping the aneurysm to exclude it from the circulation and thus preventing (re)rupture. The endovascular approach, mainly with the use of Guglielmi detachable coils, where multiple platinum coils are placed inside the CA to achieve a dense packing of the aneurysmal lumen, causes local thrombosis of the CA (10). The choice between an endovascular and surgical treatment is always made in a multidisciplinary fashion between the neurosurgeon and interventional radiologist. The International Subarachnoid Aneurysm Trial (ISAT), is the largest prospective, randomized comparative study between clipping and coiling of ruptured cerebral aneurysms, deemed amenable for both therapies, which was published in 2005. This showed that at 1 year follow-up there was no significant difference in mortality, but there was a significantly greater disability rate in the surgical group, leading to an increase of endovascular therapy for ruptured aneurysms in the ensuing years (11). Still, individual characteristics of the CA should be considered in every decision-making algorithm for their treatment. The case for unruptured aneurysms is more complex, where there is no randomized trial to date to compare surgical clipping and endovascular therapy. Again, each aneurysm should be evaluated separately in a multidisciplinary neurovascular team, where the natural history of the aneurysm, complications of the intended treatment and patient specific factors should be included. Consensus is that aneurysms with a diameter >6mm should be treated, as the rupture rate of these CA steadily increases with expanding size. The PHASES-score, based on a large meta-analsysis, was developed to assess the 5-year rupture rate of CA, based on ethnicity, presence of hypertension, age, aneurysm size, location, and evidence of previous rupture from another aneurysm (12). This of course aides the risk assessment of an incidentally found CA but doesn’t give an indication for (the type of) treatment. Etminan and colleagues produced the (eminence-based) Unruptured intracranial aneurysm treatment score, which incorporates a multitude of clinical and radiological parameters to aid clinical decision making whether to treat a CA or not (13) but again doesn’t advise the preferred type of treatment. Given the severe morbidity and mortality associated with an aneurysmal SAH, further investigation is required as for the preferred treatment choice for each individual aneurysm since, to our knowledge there is no clear consensus-study which delineates a decision-making protocol for surgical clipping versus endovascular therapy for CA. Key objectives of the doctoral thesis: 1.To review the different evidence-proven factors which advocate a clipping- or coiling based strategy, benchmark our institutional policy and results to these factors and then combining these different markers into a Delphi-consensus to be performed at a national and international level. 2. Furthermore, given the rise of endovascular options to treat these CA, the surgical exposure diminishes even further leading to scarcity of cases to teach trainees and neurosurgical vascular residents the art of surgical clipping. The lack of experience in aneurysm clipping poses a threat to the future of aneurysm treatment, where to this day, some CA are still not very well suited for endovascular solutions and require microsurgical treatment. Given this premise, it’s our goal to develop a virtual and physical real-life model which can simulate aneurysm clipping, i.e. a personalized 3D-model based on preoperative imaging studies as a teaching tool for aneurysm clipping, but also to identify and anticipate different pitfalls which might occur during surgery (width of craniotomy, approach, location of perforating vessels, …). 3. Finally, a subset of quality indicators (key performance indicators) related to aneurysm treatment in the different relevant contexts (ruptured and unruptured) will be identified to stratify the treatment outcomes for future reference and possible implementation in our own healthcare system. Bronnen: 1. Etminan N, Rinkel G. Unruptured intracranial aneurysms: development, rupture and preventive management. Nat Rev Neurol; 12, 699–713. 2. Park SH, Yim MB, Lee CY, Kim E, Son EI. Intracranial Fusiform Aneurysms: It's Pathogenesis, Clinical Characteristics and Managements. Journal of Korean Neurosurgical Society; 44 (3), 116-23. 3. Schievink W. Intracranial aneurysms. N Engl J Med; 336(1); 28-36. 4. Gasparotti, R., Liserre, R. Intracranial aneurysms. Eur Radiol; 15, 441–447. 5. Van Gijn J, Kerr R, Rinkel G. Subarachnoid haemorrhage. The Lancet; 369 (9558), 306-318. 6. Nieuwkamp D, Setz L, Algra A, et al. 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Molyneux A, Kerr R, Yu L et al.International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised comparison of effects on survival, dependency, seizures, rebleeding, subgroups, and aneurysm occlusion. Lancet; 366: 809–817 12. Greving J, Wermer M, Brown RD , et al. Development of the PHASES score for prediction of risk of rupture of intracranial aneurysms: a pooled analysis of six prospective cohort studies. Lancet Neurol; 13: 59–66. 13. Etminan N, Brown RD Jr, Beseoglu K, et al. The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus. Neurology; 85(10): 881-889.