Late reopening of adequately coiled intracranial aneurysms: frequency and risk factors in 400 patients with 440 aneurysms.

BACKGROUND AND PURPOSE: In aneurysms that are adequately occluded 6 months after coiling, the risk of late reopening is largely unknown. We assessed the occurrence of late aneurysm reopening and possible risk factors. METHODS: From January 1995 to June 2005, 1808 intracranial aneurysms were coiled in 1675 patients at 7 medical centers. At 6 months, 1066 aneurysms in 971 patients were adequately occluded. At mean 6.0 years after coiling, of the 971 patients, 400 patients with 440 aneurysms underwent 3 Tesla magnetic resonance angiography to assess occlusion status of the aneurysms. Proportions and corresponding 95% CI of aneurysm reopening and retreatment were calculated. Risk factors for late reopening were assessed by univariate and multivariate logistic regression analysis, and included patient sex, rupture status of aneurysms, aneurysm size≥10 mm, and aneurysm location. RESULTS: In 11 of 400 patients (2.8%; 95% CI, 1.4-4.9%) with 440 aneurysms (2.5%; 95% CI, 1.0-4.0%), late reopening had occurred; 3 reopened aneurysms were retreated (0.7%; 95% CI, 0.2-1.5%). Independent predictors for late reopening were aneurysm size≥10 mm (OR 4.7; 95% CI, 1.3-16.3) and location on basilar tip (OR 3.9; 95% CI, 1.1-14.6). There were no late reopenings in the 143 anterior cerebral artery aneurysms. CONCLUSIONS: For the vast majority of adequately occluded intracranial aneurysms 6 months after coiling (those<10 mm and not located on basilar tip), prolonged imaging follow-up within the first 5 to 10 years after coiling does not seem beneficial in terms of detecting reopened aneurysms that need retreatment. Whether patients might benefit from screening beyond the 5- to 10-year interval is not yet clear.

Long-term MRA follow-up after coiling of intracranial aneurysms: impact on mood and anxiety.

INTRODUCTION: Magnetic resonance angiography (MRA) screening for recurrence of a coiled intracranial aneurysm and formation of new aneurysms long-term after coiling may induce anxiety and depression. In coiled patients, we evaluated effects on mood and level of anxiety from long-term follow-up MRA in comparison to general population norms. METHODS: Of 162 patients participating in a long-term (>4.5 years) MRA follow-up after coiling, 120 completed the EQ-5D questionnaire, a visual analog health scale and a self-developed screening related questionnaire at the time of MRA. Three months later, the same questionnaires were completed by 100 of these 120 patients. Results were compared to general population norms adjusted for gender and age. RESULTS: Any problem with anxiety or depression was reported in 56 of 120 patients (47%; 95%CI38↔56%) at baseline and 42 of 100 patients (42%; 95%CI32↔52%) at 3 months, equally for screen-positives and -negatives. Compared to the reference population, participants scored 38% (95%CI9↔67%) and 27% (95%CI4↔50%) more often any problem with anxiety or depression. Three months after screening, 21% (20 of 92) of screen-negatives and 13% (one of eight) of screen-positives reported to be less afraid of subarachnoid hemorrhage (SAH) compared to before screening. One of eight screen-positives reported increased fear of SAH. CONCLUSIONS: Patients with coiled intracranial aneurysms participating in long-term MRA screening reported significantly more often to be anxious or depressed than a reference group. Screening did not significantly increase anxiety or depression temporarily. However, subjectively, patients did report an increase in anxiety caused by screening, which decreased after 3 months.

De novo aneurysm formation and growth of untreated aneurysms: a 5-year MRA follow-up in a large cohort of patients with coiled aneurysms and review of the literature.

BACKGROUND AND PURPOSE: Rates of development of de novo intracranial aneurysms and of growth of untreated additional aneurysms are largely unknown. We performed MRA in a large patient cohort with coiled aneurysms at 5-year follow-up. METHODS: In 276 patients with coiled intracranial aneurysms and 5±0.5 years of follow-up MRA (totaling 1332 follow-up patient-years), additional aneurysms were classified as unchanged, grown, de novo, or incomparable with previous imaging. We calculated 5-year cumulative incidence of de novo aneurysm formation and growth of untreated aneurysms. We searched PubMed and EMBASE databases for studies assessing aneurysm development, and growth. RESULTS: In 50 of 276 patients (18%), 75 additional aneurysms were present at follow-up MRA. Of these 75, 2 were de novo (both 3 mm), 58 were unchanged, 5 had grown from 1 to 3 mm (7.9% of 63 known additional aneurysms; 95% CI, 1.3%-14.6%), and 10 were incomparable. Five-year cumulative incidence for a de novo aneurysm developing was 0.75%. Four additional aneurysms in 3 patients were treated. Ten previous studies reported annual incidences of growth of additional aneurysms ranging from 1.51% to 22.7%, and 5 studies reported annual incidences of de novo aneurysm formation ranging from 0.3 to 1.8%. CONCLUSIONS: MRA screening of patients with coiled aneurysms within the first 5 years after treatment has a low rate of de novo aneurysm development and growth of additional aneurysms, and an even lower treatment rate.

Coiling of intracranial aneurysms: a systematic review on initial occlusion and reopening and retreatment rates.

BACKGROUND AND PURPOSE: The proportion of incompletely occluded aneurysms after coiling varies widely between studies. To assess overall outcome of coiling, we systematically reviewed the literature to determine initial occlusion, reopening, and retreatment rates of coiled aneurysms according to predefined criteria and subgroups. METHODS: We searched PubMed and EMBASE (January 1999 to September 2008) for studies of >50 coiled aneurysms. Two reviewers independently extracted data. We grouped studies reporting on only ruptured aneurysms, posterior circulation aneurysms, and studies with large proportions of aneurysms >10 mm to assess possible determinants for incomplete occlusion, reopening, and retreatment. RESULTS: Forty-six studies totalling 8161 coiled aneurysms met inclusion criteria. Immediately after coiling, 91.2% (95% CI, 90.6% to 91.9%) of the aneurysms were adequately occluded. Aneurysm reopening occurred in 20.8% (95% CI, 19.8% to 21.9%) and retreatment was performed in 10.3% (95% CI, 9.5% to 11.0%). Reopening rate was lower in studies reporting on ruptured aneurysms only compared with all studies (11.4% versus 20.8%; relative risk, 0.55; 95% CI, 0.47 to 0.64) and higher in studies focusing on posterior circulation aneurysms compared with studies with >85% anterior circulation aneurysms (22.5% versus 15.5%; relative risk, 1.5; 95% CI,1.2 to 1.7). Regression analysis showed higher retreatment rates with increasing proportion of aneurysms >10 mm (beta=0.252; 95% CI, 0.073 to 0.432). We could not find a relation between reopening and type of coils used. CONCLUSIONS: At follow-up, one fifth of all coiled intracranial aneurysms shows reopening of which half is retreated. Possible risk factors for aneurysm reopening are location in the posterior circulation and size >10 mm. To confirm our findings, a meta-analysis on individual well-reported patient data is desirable.

Depletion of resting zone chondrocytes during growth plate senescence.

With age, the growth plate undergoes senescent changes that cause linear bone growth to slow and finally cease. Based on previous indirect evidence, we hypothesized that this senescent decline occurs because growth plate stem-like cells, located in the resting zone, have a finite proliferative capacity that is gradually depleted. Consistent with this hypothesis, we found that the proliferation rate in rabbit resting zone chondrocytes (assessed by continuous 5-bromo-2'-deoxy-uridine labeling) decreases with age, as does the number of resting zone chondrocytes per area of growth plate. Glucocorticoid excess slows growth plate senescence. To explain this effect, we hypothesized that glucocorticoid inhibits resting zone chondrocyte proliferation, thus conserving their proliferative capacity. Consistent with this hypothesis, we found that dexamethasone treatment decreased the proliferation rate of rabbit resting zone chondrocytes and slowed the numerical depletion of these cells. Estrogen is known to accelerate growth plate senescence. However, we found that estradiol cypionate treatment slowed resting zone chondrocyte proliferation. Our findings support the hypotheses that growth plate senescence is caused by qualitative and quantitative depletion of stem-like cells in the resting zone and that growth-inhibiting conditions, such as glucocorticoid excess, slow senescence by slowing resting zone chondrocyte proliferation and slowing the numerical depletion of these cells, thereby conserving the proliferative capacity of the growth plate. We speculate that estrogen might accelerate senescence by a proliferation-independent mechanism, or by increasing the loss of proliferative capacity per cell cycle.

Growth plate senescence is associated with loss of DNA methylation.

The overall body size of vertebrates is primarily determined by longitudinal bone growth at the growth plate. With age, the growth plate undergoes programmed senescence, causing longitudinal bone growth to slow and eventually cease. Indirect evidence suggests that growth plate senescence occurs because stem-like cells in the growth plate resting zone have a finite proliferative capacity that is gradually exhausted. Similar limits on replication have been observed when many types of animal cells are placed in cell culture, an effect known as the Hayflick phenomenon. However, we found that the number of population doublings of rabbit resting zone chondrocytes in culture did not depend on the age of the animal from which the cells were harvested, suggesting that the mechanisms limiting replicative capacity of growth plate chondrocytes in vivo are distinct from those in vitro. We also observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo. This loss of methylation appeared to occur specifically with the slow proliferation of resting zone chondrocytes in vivo and was not observed with the rapid proliferation of proliferative zone chondrocytes in vivo (i.e. the level of DNA methylation did not change from the resting zone to the hypertrophic zone), with proliferation of chondrocytes in vitro, or with growth of the liver in vivo. Thus, the overall level of DNA methylation decreases during growth plate senescence. This finding is consistent with the hypothesis that the mechanism limiting replication of growth plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone growth in mammals, thereby determining the overall adult size of the organism.