Prospective Randomized Open-label Trial to evaluate risk faCTor management in patients with Unruptured intracranial aneurysms: Study protocol.

RATIONALE: Unruptured intracranial aneurysms are currently left untreated if the presumed complication risk of preventive endovascular or neurosurgical intervention is higher than the risk of rupture. Aneurysm wall inflammation and blood pressure are attractive modifiable risk factors of aneurysm rupture and growth. AIM: To investigate in patients with an unruptured intracranial aneurysm who do not qualify for preventive endovascular or neurosurgical intervention whether a treatment strategy of acetylsalicylic acid 100 mg/day plus intensive blood pressure treatment (targeted systolic blood pressure < 120 mmHg, monitored with a home blood pressure measuring device) reduces the risk of aneurysm rupture or growth compared with care as usual (no acetylsalicylic acid, targeted office systolic blood pressure < 140 mmHg, no home blood pressure measuring device). SAMPLE SIZE: We aim to randomize 776 patients 1:1 to the intervention arm or care as usual. DESIGN: Bi-national (Germany and the Netherlands) multicenter, prospective, randomized, open-label phase III trial with blinded outcome assessment. OUTCOMES: The primary outcome is aneurysm rupture or growth (increase in any aneurysm diameter by ≥ 1 mm) on repeated MR or CT angiography within 36 ± 6 months after randomization. DISCUSSION: The Prospective Randomized Open-label Trial to Evaluate risk faCTor management in patients with Unruptured intracranial aneurysms (PROTECT-U) is the first randomized trial to investigate if a medical strategy reduces the risk of rupture or growth of intracranial aneurysms in patients not undergoing preventive endovascular or neurosurgical aneurysm treatment. Clinical trial Registration: NCT03063541.

Microsurgical resection of Spetzler-Martin grades 1 and 2 unruptured brain arteriovenous malformations results in lower long-term morbidity and loss of quality-adjusted life-years (QALY) than conservative management--results of a single group series.

BACKGROUND: The therapeutic benefits of microsurgery for unruptured brain AVM remain unclear. METHODS: A series of 97 microsurgically resected unruptured brain AVM was analyzed in terms of postoperative morbidity and lifetime loss of quality-adjusted life-years (QALY). For comparison, the natural risk of becoming disabled was modeled on the basis of published data. RESULTS: Discharge morbidity was recorded in 11 of the 69 of Spetzler-Martin (SM) grade 1 and 2 AVMs (16 %), eight of 22 (36 %) grade 3, and four of six grade 4 (67 %), permanent morbidity >mRS 1 in 3 (4.3 %) grade 1 and 2, four (18 %) grade 3, and three (50 %) grade 4. Treatment inflicted loss of QALY amounted to 0.5 years for SM grade 1-2, 2.5 years grade 3, 7.3 years for grade 4. For the SM grades 1 and 2, the treatment-related loss of 0.5 QALY was met by the natural course after 2.7-4.3 years. For the Spetzler-Martin grades 3 and 4, the treatment-induced loss QALY was not met by the natural risk within a foreseeable time. Permanent morbidity and treatment inflicted loss of QALY of patients younger than 39 years was lower than that of older patients (7 vs. 15 % and 1.0 vs. 2.1 QALY). CONCLUSIONS: Microsurgically managed SM grades 1 and 2 fared better than the modeled natural course but grades 3 and 4 AVM did not benefit from surgery. Younger patients appear to fare more favorably than older patients.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE: To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS: After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS: Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS: Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

Microscope-integrated quantitative analysis of intraoperative indocyanine green fluorescence angiography for blood flow assessment: first experience in 30 patients.

BACKGROUND: Intraoperative measurements of cerebral blood flow are of interest during vascular neurosurgery. Near-infrared indocyanine green (ICG) fluorescence angiography was introduced for visualizing vessel patency intraoperatively. However, quantitative information has not been available. OBJECTIVE: To report our experience with a microscope with an integrated dynamic ICG fluorescence analysis system supplying semiquantitative information on blood flow. METHODS: We recorded ICG fluorescence curves of cortex and cerebral vessels using software integrated into the surgical microscope (Flow 800 software; Zeiss Pentero) in 30 patients undergoing surgery for different pathologies. The following hemodynamic parameters were assessed: maximum intensity, rise time, time to peak, time to half-maximal fluorescence, cerebral blood flow index, and transit times from arteries to cortex. RESULTS: For patients without obvious perfusion deficit, maximum fluorescence intensity was 177.7 arbitrary intensity units (AIs; 5-mg ICG bolus), mean rise time was 5.2 seconds (range, 2.9-8.2 seconds; SD, 1.3 seconds), mean time to peak was 9.4 seconds (range, 4.9-15.2 seconds; SD, 2.5 seconds), mean cerebral blood flow index was 38.6 AI/s (range, 13.5-180.6 AI/s; SD, 36.9 seconds), and mean transit time was 1.5 seconds (range, 360 milliseconds-3 seconds; SD, 0.73 seconds). For 3 patients with impaired cerebral perfusion, time to peak, rise time, and transit time between arteries and cortex were markedly prolonged (>20, >9 , and >5 seconds). In single patients, the degree of perfusion impairment could be quantified by the cerebral blood flow index ratios between normal and ischemic tissue. Transit times also reflected blood flow perturbations in arteriovenous fistulas. CONCLUSION: Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.