Serial quality of life assessment around screening for familial intracranial aneurysms: a prospective cohort study.

INTRODUCTION: Screening for intracranial aneurysms (IAs) is cost-effective in first-degree relatives of aneurysmal subarachnoid haemorrhage (aSAH) patients, but its psychosocial impact is largely unknown. PATIENTS AND METHODS: A consecutive series of persons aged 20-70 years visiting the University Medical Centre Utrecht for first screening for familial IA was approached between 2017-2020. E-questionnaires were administered at six time points, consisting of the EQ-5D for health-related quality of life (QoL), HADS for emotional functioning and USER-P for social participation. QoL outcomes were compared with the general population, and between participants with a positive and negative screening for IA. Predictors of QoL outcomes were assessed with linear mixed effects models. RESULTS: 105 participants from 75 families were included; in 10 (10%) an IA was found. During the first year after screening we found no negative effect on QoL, except for a temporary decrease in QoL six months after screening in participants with a positive screen (EQ-5D -11.3 [95%CI:-21.7 to -0.8]). Factors associated with worse QoL were psychiatric disease (EQ-5D -10.3 [95%CI:-15.1 to -5.6]), physical complaints affecting mood (EQ-5D -8.1 [95%CI:-11.7 to -4.4]), and a passive coping style (EQ-5D decrease per point increase on the Utrecht Coping List -1.1 [95%CI:-1.5 to -0.6]). DISCUSSION AND CONCLUSION: We did not find a lasting negative effect on QoL during the first year after screening for familial IA. Predictors for a worse QoL were psychiatric disease, physical complaints affecting mood, and a passive coping style. This information can be used in counselling about familial IA screening.

Radiosurgical, neurosurgical, or no intervention for cerebral cavernous malformations: A decision analysis.

INTRODUCTION: We aimed to evaluate the preferred treatment strategy for patients with symptomatic cerebral cavernous malformations (CCM). METHODS: In a decision model, we compared neurosurgical, radiosurgical, and conservative management. A literature review yielded the risks and outcomes of interventions, intracerebral hemorrhage (ICH), and seizures. Patients with CCM rated their quality of life to determine utilities. We estimated the expected number of quality-adjusted life years (QALYs) and the ICH recurrence risk over five years, according to mode of presentation and CCM location (brainstem vs. other). We performed analyses with a time horizon of five years. RESULTS: Using the best available data, the expected number of QALYs for brainstem CCM presenting with ICH or focal neurological deficit was 2.84 (95% confidence interval [CI]: 2.54-3.08) for conservative, 3.01 (95% CI: 2.86-3.16) for neurosurgical, and 3.03 (95% CI: 2.88-3.18) for radiosurgical intervention; those for non-brainstem CCM presenting with ICH or focal neurological deficit were 3.08 (95% CI: 2.85-3.31) for conservative, 3.21 (95% CI: 3.01-3.36) for neurosurgical, and 3.19 (95% CI: 2.98-3.37) for radiosurgical intervention. For CCM presenting with epilepsy, QALYs were 3.09 (95% CI: 3.03-3.16) for conservative, 3.33 (95% CI: 3.31-3.34) for neurosurgical, and 3.27 (95% CI: 3.24-3.30) for radiosurgical intervention. DISCUSSION AND CONCLUSION: For the initial five years after presentation, our study provides Class III evidence that for CCM presenting with ICH or focal neurological deficit conservative management is the first option, and for CCM presenting with epilepsy CCM intervention should be considered. More comparative studies with long-term follow-up are needed.

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.

A cost-effectiveness analysis of screening for intracranial aneurysms in persons with one first-degree relative with subarachnoid haemorrhage.

INTRODUCTION: Although persons with one first-degree relative with aneurysmal subarachnoid haemorrhage have an increased risk of aneurysm formation and aneurysmal subarachnoid haemorrhage, screening them for unruptured intracranial aneurysms was not beneficial in a modelling study from the 1990s. New data on the risk of aneurysmal subarachnoid haemorrhage in these persons and improved treatment techniques call for reassessment of the cost-effectiveness of screening. PATIENTS AND METHODS: We used a cost-effectiveness analysis using a Markov model and Monte Carlo simulation comparing screening and preventive aneurysm treatment with no screening in persons with one first-degree relative with aneurysmal subarachnoid haemorrhage. We analyzed the impact on quality-adjusted life years, costs and net health benefit of single screening (at varying screening age) and serial screening (with varying screening age and intervals) using a cost-effectiveness threshold of €20,000/quality-adjusted life year. RESULTS: In 17 of the 24 strategies assessed, additional costs for screening for unruptured intracranial aneurysm were <€20,000 per quality-adjusted life year gained. The strategy with highest net health benefit was screening at age 40 and 55. Screening every five years from age 20 to 70 yielded the highest health benefits at the highest additional costs. DISCUSSION: Based on current risks of aneurysmal subarachnoid haemorrhage and complications of preventive treatment, several strategies to screen for unruptured intracranial aneurysm in persons with one first-degree relative with aneurysmal subarachnoid haemorrhage are cost effective compared with no screening, when applying a cost-effectiveness threshold of €20,000/quality-adjusted life year. CONCLUSION: We recommend discussing with persons at risk the option of screening twice, at age 40 and 55, which will result overall in substantial health benefits at acceptable additional costs.