Laura T. van der Kamp

Background: Tiny unruptured intracranial aneurysms, defined as ⩽ 3 mm, are increasingly detected due to advancements in imaging. However, the optimal management approach remains uncertain. Studies have questioned the necessity of long-term radiological monitoring because of presumed low risks of growth, yet robust data are limited. Aims: This retrospective cohort study aimed to estimate the 5-year growth risk of conservatively managed tiny unruptured intracranial aneurysms and assess potential differences in growth between men and women. Methods: We conducted a single-center retrospective cohort study including adult patients diagnosed with one or more tiny saccular unruptured intracranial aneurysms at a tertiary academic hospital between 2008 and 2020. Patients were included if at least two imaging studies (baseline and ⩾1 follow-up) were available. Growth was defined as a ⩾1 mm increase in size or a morphological change. Growth risk was calculated, and cumulative incidence was estimated using the Kaplan–Meier analysis. Sex differences were analyzed using the log-rank tests. Results: A total of 182 patients (142 women; median age = 54 years) with 228 tiny unruptured intracranial aneurysms were followed for a median of 5.5 years. Growth was observed in 29 unruptured intracranial aneurysms (12.7%). The Kaplan–Meier analysis showed cumulative growth of 9.7% (95% confidence interval = 5.1–14.2%) at 5 years. Growth rates were comparable between men and women (p = 0.63). Conclusions: Approximately one in eight tiny unruptured intracranial aneurysms demonstrated growth over long-term follow-up, indicating a clinically relevant growth risk despite small initial size. No sex-related differences in growth were observed. These findings support the importance of long-term radiological monitoring. Future studies should investigate whether tiny unruptured intracranial aneurysms may be safely followed with longer surveillance intervals than larger unruptured intracranial aneurysms. Data access statement: The data underlying this study are not publicly available due to institutional and ethical restrictions but may be accessed upon reasonable request and subject to approval by the appropriate review committees.

Objective: Aneurysm wall enhancement (AWE) may predict aneurysm growth and rupture in the short‐term, but there is a lack of long‐term follow‐up studies. We aimed to determine whether unruptured intracranial aneurysms (UIAs) with AWE have a higher probability of aneurysm instability during long‐term follow‐up compared with those without AWE. Methods: For this longitudinal cohort study, we obtained individual patient data from two international cohorts. We included patients with ≥ 1 untreated UIA who underwent gadolinium‐enhanced aneurysm wall imaging and magnetic resonance angiography (MRA) between 2012 and 2016, and had follow‐up imaging and/or had a rupture during follow‐up. The outcome was aneurysm instability, defined as time to growth, morphological change, or rupture during follow‐up. We calculated the 7.5‐year probability of aneurysm instability with 95% confidence interval (CI) with the Kaplan–Meier estimator. We used Cox regression survival analysis to calculate the crude hazard ratio (HR) with corresponding 95% CI of AWE for aneurysm instability, and the HR adjusted for age and aneurysm size at baseline. Results: We included 198 patients (median age = 58 years, interquartile range = 50–68, 139 women, 70%) with 224 aneurysms. Aneurysm instability was observed in 15 of 72 aneurysms (21%) with AWE and 13 of 152 aneurysms (9%) without AWE during a median follow‐up duration of 6.8 years (IQR = 3.3–7.9). The 7.5‐year probability of instability was 29.2% (95% CI = 14.5%–41.3%) in aneurysms with AWE and 9.3% (95% CI = 2.9%–15.3%) in aneurysms without AWE (crude HR = 4.29, 95% CI = 1.90–9.72, adjusted HR = 5.06, 95% CI = 2.13–12.02). Interpretation: UIAs with AWE have a higher probability of 7.5‐year aneurysm instability compared with those without AWE. ANN NEUROL 2026;99:863–870

BACKGROUND AND PURPOSE: Aneurysm wall enhancement on MRI after administration of gadolinium is associated with aneurysm growth or rupture. Aneurysm wall enhancement has mostly been studied at baseline. The change in the presence or absence of aneurysm wall enhancement with time is largely unknown but can provide a better understanding of the pathophysiological processes occurring within the aneurysm wall. Therefore, we aimed to determine the proportion of aneurysm wall enhancement appearance or disappearance. MATERIALS AND METHODS: In this multicenter cohort study, we analyzed individual patient data from 11 international cohorts. Patients 18 years of age or older with at least 1 untreated saccular unruptured intracranial aneurysm were included if they had 2 consecutive MRIs with aneurysm wall imaging. A Wilson score interval was used to calculate confidence intervals for the proportion of aneurysms with aneurysm wall enhancement changes, defined as appearance or disappearance between the 2 MRIs. RESULTS: We included 305 patients with 387 unruptured intracranial aneurysms. Aneurysm wall enhancement was present at baseline in 142 (37%) aneurysms in 122 patients. Aneurysm wall enhancement appeared or disappeared in 20/387 aneurysms (5.2% [95% CI, 3.4–7.8]) after a median follow-up of 12 months (interquartile range, 5–13). Of the 245 aneurysms without enhancement at baseline, 13 (5.3% [95% CI, 3.1–8.9]) had the appearance of wall enhancement at the second MR aneurysm wall imaging. Of the 142 aneurysms with aneurysm wall enhancement at baseline, 7 aneurysms (4.9% [95% CI, 2.4–9.8]) had the disappearance of aneurysm wall enhancement. CONCLUSIONS: Most unruptured intracranial aneurysms have persistent presence or absence of aneurysm wall enhancement during a median 1-year follow-up period. This finding suggests that underlying pathophysiological processes in the aneurysm wall are long-lasting. Graphical Abstract

BACKGROUND AND PURPOSE: Previous studies showed that intracranial aneurysm wall enhancement (AWE) is associated with aneurysm growth or rupture. These studies assessed growth with manual 2D measurements or eyeballing, both of which are prone to interobserver variability. To minimize this variability, we assessed the association between AWE and semi-automatically quantified 3D morphological changes in aneurysms during long-term follow-up. MATERIALS AND METHODS: We included patients with an unruptured intracranial aneurysm who had baseline MR aneurysm wall imaging and were followed with MR or CT angiography for ≥1 year. We used in-house-developed software to measure six 3D morphological parameters on paired baseline and follow-up scans and determined changes over time. We compared the proportion of aneurysms showing morphological change (modified Z-score <-3.5 or >+3.5) between aneurysms with and without AWE. The risk difference with 95% CI was calculated for each morphological parameter. For parameters with a statistically significant change difference between aneurysms with and without AWE, we calculated ORs with 95% CI in a univariable logistic regression model, and adjusted for aneurysm size in a bivariable model. RESULTS: Sixty-two patients with 72 unruptured intracranial aneurysms met inclusion criteria. Twenty aneurysms (28%) in 18 patients showed AWE at baseline. Median follow-up was 5.8 years (IQR 4.6–6.6). For the parameter curvedness, the proportion of aneurysms showing an increase was higher in aneurysms with AWE (6 of 20, 30%) than aneurysms without AWE (2 of 52, 4%), with a risk difference of 26% (95%CI 9–49%). For the other five morphological parameters, the proportion of aneurysms with morphological change was comparable between aneurysms with and without AWE. In logistic regression analysis, AWE was associated with curvedness increase (crude OR 10.7 [95%CI 2.2–78.9], adjusted OR 6.1 [95%CI 1.01–50.3]). CONCLUSIONS: AWE was associated with aneurysm shape change during long-term follow-up, with an increase in 3D quantified curvedness that was independent of aneurysm size. This reinforces previous findings that AWE is associated with aneurysm instability, in particular curvedness increase, and suggests that curvedness could be a suitable parameter to capture aneurysm instability. Future studies need to investigate whether an increase in this parameter predicts aneurysmal rupture. ABBREVIATIONS: AWE = aneurysm wall enhancement; AWI = aneurysm wall imaging; IBSI = imaging biomarker standardization initiative; UIA = unruptured intracranial aneurysm.

BACKGROUND AND PURPOSE: The performance of current prediction models for intracranial aneurysm growth and rupture is suboptimal, and new markers are needed to improve prediction. There is a strong need for longitudinal studies that use standardized morphological parameters. In this longitudinal study, we aimed to identify standardized three-dimensional (3D) quantified morphological parameters as predictors of aneurysm growth or rupture during long-term follow-up. MATERIALS AND METHODS: We used a database of consecutive patients with saccular unruptured intracranial aneurysms diagnosed between 2008–2018. Employing a retrospective case-cohort design, we included a computer-generated random sample of aneurysms from the full cohort and aneurysms with growth or rupture during follow-up outside the random sample. The case-cohort design is efficient for low-incidence outcomes while maintaining the temporal association between exposure and outcome. Aneurysms were annotated on baseline CTA or MRA images, and 3D morphological parameters were quantified. Univariable and multivariable Cox proportional hazards models were used to identify 3D morphological predictors of either aneurysm growth or aneurysm rupture. An inverse sampling probability weight was applied to obtain unbiased estimates of the hazard ratios. RESULTS: We included 278 patients (median age, 59 years [IQR50-66]; 209 women) with 327 aneurysms, of which 239 aneurysms were stable during follow-up (73%), 68 grew without subsequent rupture (21%), 7 grew with subsequent rupture (2%), and 13 ruptured without preceding growth (4%). In the multivariable model for growth prediction (median follow-up 4.1 years [IQR1.9–7.1]), 2 parameters were retained: major axis (HR 1.16, 95%CI: 0.84–1.61) and shape index (HR 1.53, 95%CI: 0.76–3.08), with a c-statistic of 0.56 (95%CI: 0.49–0.63). The same parameters were retained in the multivariable model for prediction of rupture (median follow-up 4.5 years [IQR2.1–7.3]): major axis (HR 2.27, 95%CI: 1.36–3.80) and shape index (HR 3.33, 95%CI: 0.95–11.62), with a c-statistic of 0.85 (95%CI: 0.77–0.94). CONCLUSIONS: We identified major axis and shape index as candidate 3D quantified morphological predictors of both aneurysm growth and rupture, but only for rupture these had good discriminative power in our cohort. These parameters will need external validation and should be integrated with existing clinical prediction models. ABBREVIATIONS: ELAPSS = Earlier subarachnoid hemorrhage, Location of the aneurysm, Age, Population, Size of the aneurysm, and Shape of the aneurysm; IBSI = imaging biomarker standardization initiative; PHASES = Population, Hypertension, Age, Size of aneurysm, Earlier SAH from another aneurysm, and Site of aneurysm; UIA = unruptured intracranial aneurysm.

Objectives: In patients with an unruptured intracranial aneurysm, gadolinium enhancement of the aneurysm wall is associated with growth and rupture. However, most previous studies did not have a longitudinal design and did not adjust for aneurysm size, which is the main predictor of aneurysm instability and the most important determinant of wall enhancement. We investigated whether aneurysm wall enhancement predicts aneurysm growth and rupture during follow-up and whether the predictive value was independent of aneurysm size. Materials and methods: In this multicentre longitudinal cohort study, individual patient data were obtained from twelve international cohorts. Inclusion criteria were as follows: 18 years or older with ≥ 1 untreated unruptured intracranial aneurysm < 15 mm; gadolinium-enhanced aneurysm wall imaging and MRA at baseline; and MRA or rupture during follow-up. Patients were included between November 2012 and November 2019. We calculated crude hazard ratios with 95%CI of aneurysm wall enhancement for growth (≥ 1 mm increase) or rupture and adjusted for aneurysm size. Results: In 455 patients (mean age (SD), 60 (13) years; 323 (71%) women) with 559 aneurysms, growth or rupture occurred in 13/194 (6.7%) aneurysms with wall enhancement and in 9/365 (2.5%) aneurysms without enhancement (crude hazard ratio 3.1 [95%CI: 1.3–7.4], adjusted hazard ratio 1.4 [95%CI: 0.5–3.7]) with a median follow-up duration of 1.2 years. Conclusions: Gadolinium enhancement of the aneurysm wall predicts aneurysm growth or rupture during short-term follow-up, but not independent of aneurysm size. Clinical relevance statement: Gadolinium-enhanced aneurysm wall imaging is not recommended for short-term prediction of growth and rupture, since it appears to have no additional value to conventional predictors. Graphical Key Points: • Although aneurysm wall enhancement is associated with aneurysm instability in cross-sectional studies, it remains unknown whether it predicts risk of aneurysm growth or rupture in longitudinal studies. • Gadolinium enhancement of the aneurysm wall predicts aneurysm growth or rupture during short-term follow-up, but not when adjusting for aneurysm size. • While gadolinium-enhanced aneurysm wall imaging is not recommended for short-term prediction of growth and rupture, it may hold potential for aneurysms smaller than 7 mm.

Unruptured intracranial aneurysms (UIAs) occur in approximately 3% of the adult population.¹ The number of incidentally discovered UIAs has increased owing to the rising availability and use of brain imaging.² Most UIAs are smaller than 7 mm and have a low risk of rupture.³ Preventive endovascular or neurosurgical aneurysm treatment is often considered, but these treatment options carry a substantial risk of procedure-related complications.⁴ In many patients with small aneurysms, the aneurysm remains untreated because the risk of treatment complications is estimated to be higher than the risk of rupture. Most of these patients are monitored over time with repeated magnetic resonance angiography or computed tomography angiography to detect aneurysm growth. If aneurysm growth is detected, the aneurysm is often treated. This policy is based on observations that aneurysms with detected growth have a higher risk of rupture than aneurysms without growth.^5-10 Although the relative risk of rupture after detection of growth is increased, the absolute risk of rupture after detection of aneurysm growth is unknown. This absolute risk is pivotal for consultation with patients after detection of growth of the aneurysm, because the risk of rupture needs to be weighed against the risk of treatment complications. The purpose of this multicenter cohort study was to determine the absolute risk of rupture of an aneurysm after detection of growth on follow-up imaging and to develop a prediction model for rupture based on predictors of rupture.

Introduction: eConsultation in nephrology is an innovative way for general practitioners (GPs) to consult a nephrologist. Studies have shown that questions from GPs can be answered and intended referrals can be avoided by eConsultation. However, follow-up data are lacking. The primary aim of this study was therefore to assess whether patients for whom a referral to the outpatient clinic of a medical specialist was avoided in the short term were not then referred for the same problem within one year after the eConsultation. Methods: All eConsultations sent between June 2017 and April 2018 to seven nephrologists in three different hospitals in The Netherlands were included. Exclusion criteria were duplications and missing data on follow-up. Data were obtained from the eConsultation application forms and from GP medical records. Results: A total of 173 eConsultations were included. Of the 32 patients for whom a referral was initially prevented, 91% (95% confidence interval 75–98) had not been referred to a specialist for the same problem within one year after the eConsultation. Discussion: eConsultation in the field of nephrology can prevent referrals in the long term. It can therefore contribute to a more modern and efficient health-care system in which chronic care is provided by GPs in close proximity to patients, while specialist support is easily available and accessible through eConsultation when necessary.

This study aimed to define the prevalence and predictors of non-right-handedness and its link to long-term neurodevelopmental outcome and early neuroimaging in a cohort of children born extremely preterm (<28 weeks gestation). 179 children born extremely preterm admitted to the Neonatal Intensive Care Unit of our tertiary centre from 2006–2013 were included in a prospective longitudinal cohort study. Collected data included perinatal data, demographic characteristics, neurodevelopmental outcome measured by the Bayley Scales of Infant and Toddler Development at 2 years and the Movement Assessment Battery for Children at 5 years, and handedness measured at school age (4–8 years). Magnetic resonance imaging performed at term-equivalent age was used to study overt brain injury. Diffusion tensor imaging scans were analysed using tract-based spatial statistics to assess white matter microstructure in relation to handedness and neurodevelopmental outcome. The prevalence of non-right-handedness in our cohort was 22.9%, compared to 12% in the general population. Weaker fine motor skills at 2 years and paternal non-right-handedness were significantly associated with non-right-handedness. Both overt brain injury and fractional anisotropy of white matter structures on diffusion tensor images were not related to handedness. Fractional anisotropy measurements showed significant associations with neurodevelopmental outcome. Our data show that non-right-handedness in children born extremely preterm occurs almost twice as frequently as in the general population. In the studied population, non-right-handedness is associated with weaker fine motor skills and paternal non-right-handedness, but not with overt brain injury or microstructural brain development on early magnetic resonance imaging.