Sanne Van Rooij

In Chapter 1 an introduction and outline of the thesis is provided.

In Chapter 2 we provide an update of hospital demographics of patients with intracranial hemorrhage and suspected vascular disorders with 3D angiography as the golden standard. Clinical outcome data were available for 284 patients over a time-span of 2 years. In patients with aneurysms, characteristics and mode of treatment were recorded. In 197 of 220 patients with an aneurysmal bleeding pattern a cause of the bleeding was found: 195 patients had a ruptured aneurysm (98%), 1 patient a micro AVM and 1 patient reversible vasoconstriction syndrome. Of 195 ruptured aneurysms, 6 were dissection aneurysms and 3 were AVM associated flow aneurysms. In 23 of 204 patients (11%) with an aneurysmal bleeding pattern and 3DRA performed no cause was found. In 8 of 9 patients (89%) with a positive lumbar puncture but negative CT, no cause was found. Of 180 patients with a ruptured aneurysm eligible for treatment, 147 (82%) were treated endovascular and 30 (17%) were clipped. Of 204 patients with an aneurysmal bleeding pattern and 3DRA, 72 (35%) had multiple aneurysms. These 72 patients had altogether 117 additional aneurysms of which 24 (21%) were treated either by coiling or clipping. This study provides robust data on hospital demographics of SAH in a neurosurgical referral center, based on CTA and 3D Rotational Angiography of all vessels. We found that new 3D imaging techniques provide more accurate diagnosis and endovascular treatment has largely replaced surgery.

Chapter 3 describes the diagnostic accuracy of CTA in the detection of intracranial aneurysms and other vascular disorders in consecutive patients with acute SAH in 179 patients. One hundred thirty-nine patients with acute SAH underwent CTA followed by 3DRA. We compared CTA with 3DRA of all cerebral vessels. In 118 of 139 patients (85 %), 3DRA diagnosed the cause of hemorrhage: 113 ruptured aneurysms, three arterial dissections, one micro-arteriovenous malformation (AVM), and one reversible vasoconstriction syndrome. On CTA, both observers missed all five non-aneurysmal causes of SAH. The sensitivity of CTA in depicting ruptured aneurysms was 0.88–0.91, and accuracy was 0.88–0.92. Of 113 ruptured aneurysms, 28 were ≤3 mm (25 %) and of 95 additional aneurysms, 71 were ≤3 mm (75 %). The sensitivity of depicting aneurysms ≤3 mm was 0.28–0.43. Of 95 additional aneurysms, the two raters missed 65 (68 %) and 58 (61 %). Sensitivity in detection was lower in aneurysms of the internal carotid artery than in other locations. CTA had some limitations as a primary diagnostic tool in patients with SAH. All non-aneurysmal causes for SAH and one in ten ruptured aneurysms were missed. The performance of CTA was poor in aneurysms ≤3 mm. The majority of additional aneurysms were not depicted on CTA.

In Chapter 4 we assess with 3DRA the prevalence and location of fenestrations of intracranial arteries and the relation with aneurysms in a cohort of 208 patients. In 59 of 208 patients, 61 fenestrations were detected (28%). Fenestrations were more frequent in the anterior than in the posterior circulation (23% versus 7%), and the most common location was the anterior communicating artery (Acoma) (43 of 61, 70%). The frequency of fenestrations in 185 patients with aneurysms was not different from the frequency in 23 patients without aneurysms. Of 220 aneurysms present in 208 patients, 10 aneurysms (4.5%) were located on a fenestration. Of 61 fenestrations, 51 (84%) were not associated with an aneurysm. A definite relationship between fenestrations and aneurysms cannot be concluded from our data.

Chapter 5 reports the clinical- and imaging results of 100 patients (71 women, mean age 59 years) with a ruptured aneurysm treated with the WEB regardless of aneurysm location or neck size. No supporting stents or balloons were used. The mean aneurysm size was 5.6 mm (range 3-13 mm) and 42 aneurysms were ≤4mm. Sixty-six aneurysms (66%) had a wide neck defined as ≥4 mm or dome-neck ratio ≤ 1.5. There was 1 procedural rupture without sequelae. In 9 patients (9%), thromboembolic complications occurred. One poor grade patient died, neurological deficits remained in 3. The overall treatment-related morbidity-mortality was 4% (4 of 100; 95% CI, 1.2%-10.2%). Of 80 eligible patients, 74 (93%) had 3 months’ angiographic follow-up. Fifty-four aneurysms (73%) were completely occluded, 17 (23%) had a small neck remnant and 3 (4%) were incompletely occluded. One patient was additionally treated with a second WEB and in 2 patients additional treatment is scheduled. Overall reopening/retreatment rate was 6.8% (5 of 74, 95%CI 2.6-15.2%). There were no rebleeds during follow-up. WEB treatment of ruptured aneurysms is feasible, effective and safe. The WEB proved a valuable alternative to coils and it allowed us to refrain from the use of adjunctive stents and supporting balloons.

In Chapter 6, we evaluated the clinical and imaging results of the WEB as a primary treatment for 59 unruptured intracranial aneurysms. We treated all aneurysms suitable for the device, regardless of neck size and location. There were 15 men and 36 women with a mean age of 59 years. The mean aneurysm size was 7.0 mm (range 3-22 mm). Of 59 aneurysms, 45 (76%) had a wide neck defined as ≥4 mm or dome-neck ratio ≤ 1.5. No stents or supporting balloons were used. The initial WEB position was judged good in all 59 unruptured aneurysms. One patient with a basilar tip aneurysm had a late thrombotic posterior cerebral artery occlusion by a protrusion of the WEB over the artery. There were no procedural ruptures. Overall complication rate was 2.0% (1 of 51, 95%CI 0.01-11.3%). Imaging follow-up was available in 55 of 59 aneurysms (93%). At 3 months, 41 of 57 aneurysms (72%) were completely occluded, 12 (21%) had a neck remnant and 4 (7%) were incompletely occluded. WEB treatment is safe and effective in selected unruptured aneurysms suitable for the device, regardless of neck size or location. There was no need for supportive devices. In our opinion, the WEB is a valuable alternative to coils, especially in wide-necked aneurysms.

In Chapter 7, we present the first clinical and imaging results of the treatment of 46 ruptured and unruptured aneurysms with the new low-profile WEB 17. The WEB 17 was developed to improve technical performance in tortuous vasculature and for (very) small aneurysms. Between December 2016 and September 2017, 46 aneurysms in 40 patients were treated with the WEB 17. There were 6 men and 34 women, mean age 62 years (median 63, range 46-87). No supporting stents or balloons were used. Twenty-five aneurysms were ruptured (54%). The mean aneurysm size was 4.9 mm (median 5, range 2-7 mm). There were 2 thrombo-embolic procedural complications without clinical sequelae and no ruptures. Overall permanent procedural complication rate was 0% (0 of 40, 97.5%CI 0-10.4%). Imaging follow-up at 3 months was available in 33 patients with 39 aneurysms (97.5% of eligible aneurysms). In one aneurysm the detached WEB was undersized and the remnant was additionally treated with coils after 1 week. This same aneurysm reopened at 3 months and was again treated with a second WEB. One other aneurysm showed persistent WEB filling at 3 months. Complete occlusion was achieved in 28 aneurysms (72%) and 9 aneurysms (23%) showed a neck-remnant. WEB 17 was safe and effective for both ruptured and unruptured aneurysms. The WEB 17 proved a valuable addition to the existing WEB size range, especially for very small aneurysms.

In Chapter 8, Magnetic Resonance Angiography (3T MRA) was used for mid-term follow-up of WEB-treated aneurysms that were adequately occluded at 3 months angiographic follow-up. Included were 52 patients with 53 aneurysms treated with the WEB between February 2015 and July 2016. There were 29 women and 23 men with a mean age of 60 years. The mean aneurysm size was 6.2 mm. 3T MRA follow-up was mean 19.6 months (median 18, range 18–36 months). One patient had an aneurysm remnant at 3 months' angiography that was additionally coiled and with stable complete occlusion at 18 months' 3T MRA follow- up. At three-month follow-up angiography, 44 aneurysms were completely occluded and eight had a neck remnant. At the latest 3T MRA, stable complete occlusion was present in 43 aneurysms and stable neck remnant in eight. One posterior cerebral artery (PCA) dissection aneurysm was stable at three and six months but was enlarged and reopened at 18 months, confirmed with angiography. Focal signal loss by the proximal marker of the WEB was apparent in four patients without compromising diagnostic evaluation. WEB-treated aneurysms with adequate occlusion at three-month angiography remained stable during serial 3T MRA follow-up of 18–36 months. One PCA aneurysm reopened during the 6- to 18-month interval. Once the WEB-treated aneurysm is adequately occluded in the short term, later reopening is uncommon.

In Chapter 9, a systematic review and meta-analysis were presented to evaluate the outcomes of the new generation low-profile WEB Single Layer device for intracranial aneurysm treatment. Fifteen papers were identified reporting the use of WEB SL devices in 963 aneurysms, mostly wide-neck bifurcation aneurysms. Procedural aneurysm rupture was reported in 8 of 963 patients (0.83%; 95%CI 0.39-1.66%) and thromboembolic events in 54 of 963 patients (5.61%, 95CI 4.31-7.26%). Cumulative morbidity was 2.85 % (27/949, 95%CI 1.95-4.12%) and mortality 0.93% (9/963, 95%CI 0.46-1.80%). The overall rate of adequate aneurysm occlusion at last follow-up was 83.3% (613/736; 95%CI 80.4-85.8%). Retreatment was reported in 38 aneurysms in 8 studies with 450 aneurysms with follow-up (38/450; 8.4%, 95CI 6.2-11-4%). In 12 studies comprising 644 aneurysms with follow-up, rebleeds occurred in 3 patients in 3 studies with mean follow-up between 3.3 and 14.4 months (0.47%, 95%CI 0.09-1.43%). WEB SL is a promising new low profile device especially for wide-neck bifurcation aneurysms, both ruptured and unruptured. No antiplatelet medication is needed which is a great advantage, especially in ruptured aneurysms. Efficacy and safety compare favorably with (stent-assisted) coiling. However, no direct comparison with other treatments is available as yet.

In Chapter 10, the findings of this thesis are generally discussed and possible future directions are outlined.