Introduction and historical background 11 In 1765, Biumi of Milan provided the first clinical account and autopsy description of an aneurysmal subarachnoid hemorrhage (SAH)1. SAH is a devastating neurologic disorder leading to a high mortality rate, permanent disability in 50% of surviving patients, and estimated lifetime costs amounting to more than double those of an ischemic stroke.2-4 A patient showing signs and symptoms indicating a possible SAH poses several diagnostic challenges: At first the clinical presentation of SAH is not always straightforward and the classic symptomatic “thunderclap headache” characterizing SAH may be absent or caused by another disease.5 A definite diagnosis therefore, can only be established through imaging or laboratory tests of the cerebrospinal fluid (CSF). A rapid and accurate diagnosis is crucial since one of the possible underlying causes of SAH is a potentially fatal, but treatable, intracranial aneurysm. Thus, once the diagnosis SAH has been confirmed, the second challenge is to detect or exclude an aneurysm as the cause of hemorrhage. If an aneurysm is found, the third challenge is to select the most appropriate treatment: endovascular or neurosurgical. The aim of the treatment is to prevent a new bleed from the aneurysm, the risk of which is greatest in the period immediately following the first bleed. After treatment a follow-up strategy is needed to detect possible aneurysm recurrence. Finding the optimal follow-up strategy is the fourth challenge. In the last decennia, much research has been carried out and many articles have been published on the ways in which these challenges can be met. This thesis contributes to our understanding and overcoming of those challenges. Epidemiology of Intracranial aneurysms From a meta-analysis of 68 studies it was calculated that the prevalence of intracranial aneurysms was 3.2 % in a hypothetical population with no co-morbidity, a mean age of 50 years and a 1:1 sex ratio (95%CI 1.9-5.2).6 Other studies found a prevalence of intracranial aneurysms ranging from 2 to 3%.7-9 The prevalence is higher in patients with connective tissue disorders such as autosomal dominant polycystic kidney disease (ADPKD) or Ehlers-Danlos disease, and in patients with a family history of one or more known intracranial aneurysms: prevalence is estimated to be 4 – 10 % for patients with a case in one first-degree relative, and 20 % for patients with more than one case in their family history. 6,7 Even though nowadays more and more aneurysms are being detected through screening or as incidental findings, the majority of aneurysms manifest themselves through rupturing into the subarachnoid space surrounding the intracranial arteries. Retrospective calculations on the average risk of aneurysm rupture have been carried out in the International Study of Unruptured Intracranial Aneurysms (ISUIA)10,11 and other investigations.12-14 These have led to estimates of annual risk of rupture ranging from 0.3% for small (<7mm) anterior circulation aneurysms, to 13.0% for large (>25mm) posterior circulation aneurysms10, and even to 43.1% for large aneurysms in the Japanese population.12 Worldwide incidence of aneurysmal SAH is approximately 9/100,000 patient years (PY), with a wide range of variability per region from 2.0 and 4.2/100,000 PY in China and Central & South America, to 19.7 and 22.7/100,000 PY in Finland and Japan.15,16 Incidence of aneurysmal SAH in the Netherlands is 3.78 / 100,000 PY (2.98-4.72).17 The high incidence of SAH in Finland and Japan is not associated with a
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