Willem Jan van Rooij

Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial

BACKGROUND Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. METHODS Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. FINDINGS Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was -5·2 (95% CI -5·88 to -4·72) after vertebroplasty and -2·7 (-3·22 to -1·98) after conservative treatment, and between baseline and 1 year was -5·7 (-6·22 to -4·98) after vertebroplasty and -3·7 (-4·35 to -3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74-3·37, p<0·0001) at 1 month and 2·0 (1·13-2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. INTERPRETATION In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. FUNDING ZonMw; COOK Medical.

Treatment of Intracranial Aneurysms by Embolization with Coils A Systematic Review

BACKGROUND Embolization with coils is increasingly used for the treatment of intracranial aneurysms. To assess the percentage of complications, the percentage of aneurysm occlusion, and the short-term outcome, we performed a systematic review of studies on embolization with controlled detachable or pushable coils. SUMMARY OF REVIEW To find studies on embolization with coils, we performed a MEDLINE search from January 1990 to March 1997, checked all reference lists of the studies found, performed a Science Citation Index search on Guglielmi, and hand searched recent volumes of 25 journals. Two authors independently extracted data by means of a standardized data extraction form from 48 eligible studies totalling 1383 patients. Permanent complications of embolization with controlled detachable coils occurred in 46 of 1256 patients (3.7%; 95% CI, 2.7% to 4.9%); 400 of 744 aneurysms (54%; 95% CI, 50% to 57%) were completely occluded. By means of weighted linear regression, no relation between baseline characteristics and outcome measurements was found. The results in the prespecified subgroups of patients with a ruptured aneurysm, an unruptured aneurysm, or a basilar bifurcation aneurysm were essentially the same as the overall results. CONCLUSIONS Short-term results indicate that embolization with coils is a reasonably safe treatment for patients with an unruptured aneurysm and for patients with aneurysmal subarachnoid hemorrhage. The effectiveness in terms of complete occlusion of the aneurysm is moderate. Randomized trials are warranted to compare surgical clipping with embolization with coils.

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 (β=0.252; 95% CI, 0.073 to 0.432). We could not find a relation between reopening and type of coils used. Conclusion— 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. # Supplemental Appendix {#article-title-2}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 (&bgr;=0.252; 95% CI, 0.073 to 0.432). We could not find a relation between reopening and type of coils used. Conclusion— 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.

The relation between packing and reopening in coiled intracranial aneurysms : a prospective study

AbstractWe evaluated prospectively the relation between packing and reopening in coiled intracranial aneurysms. Packing, defined as the ratio between the volume of inserted coils and volume of the aneurysm expressed as percentage, was calculated for 82 intracranial aneurysms treated with detachable coils. Aneurysm volume was assessed from 3D angiography. Reopening of the aneurysmal lumen at the 6-month follow-up angiography was dichotomized into present or absent. We assessed whether packing above 24% protected against reopening. Twenty-three of 82 aneurysms (28%) showed reopening. Reopening was caused by compaction in 20 aneurysms and by partial thrombosis, undetected at the time of initial treatment in three aneurysms. Three of 29 aneurysms (10%) with a packing of more than 24% showed reopening. These three aneurysms contained partially intraluminal thrombosis undetected at the time of treatment. We conclude that in coiled intracranial aneurysms packing above 24% protects against reopening by compaction in non-thrombosed aneurysms. Since intraluminal thrombosis may go undetected at the time of treatment, follow-up angiography is still warranted in aneurysms with packing densities greater than 24%.

Long-Term Recurrent Subarachnoid Hemorrhage After Adequate Coiling Versus Clipping of Ruptured Intracranial Aneurysms

BACKGROUND AND PURPOSE Coiling is increasingly used as treatment for intracranial aneurysms. Despite its favorable short-term outcome, concerns exist about long-term reopening and inherent risk of recurrent subarachnoid hemorrhage (SAH). We hypothesized a higher risk for recurrent SAH after adequate coiling compared with clipping. METHODS Patients with ruptured intracranial aneurysms coiled between 1994 and 2002 with adequate (>90%) aneurysm occlusion at 6-month follow-up angiograms were included. We interviewed these patients about new episodes of SAH. By survival analysis, we assessed the cumulative incidence of recurrent SAH after coiling and compared it with the incidence of recurrent SAH in a cohort of 748 patients with clipped aneurysms by calculating age and sex-adjusted hazard ratios. RESULTS Of 283 coiled patients with a total follow-up of 1778 patient-years (mean, 6.3 years), one patient had a recurrent SAH (0.4%) and 2 patients had a possible recurrent SAH. For recurrent SAH within the first 8 years after treatment, the cumulative incidence was 0.4% (95% CI, -0.4 to 1.2) after coiling versus 2.6% (95% CI, 1.2 to 4.0) after clipping (hazard ratio, 0.2; 95% CI, 0.03 to 1.6). For possible and confirmed recurrent SAH combined, the cumulative incidence was 0.7% (95% CI, 0.3 to 1.7) after coiling versus 3.0% (95% CI, 1.3 to 4.6) after clipping (hazard ratio, 0.7; 95% CI, 0.2 to 2.3). CONCLUSIONS Patients with adequately occluded aneurysms by coiling at short-term follow-up are at low risk for recurrent SAH in the long term. Within the first 8 years after treatment, the risk of recurrent SAH is not higher after adequate coiling than after clipping.

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.

A randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures (VERTOS IV)

BackgroundThe standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is a new treatment option. Recent randomized controlled trials (RCT) provide conflicting results: two sham-controlled studies showed no benefit of PV while an unmasked but controlled RCT (VERTOS II) found effective pain relief at acceptable costs. The objective of this study is to compare pain relief after PV with a sham intervention in selected patients with an acute osteoporotic VCF using the same strict inclusion criteria as in VERTOS II. Secondary outcome measures are back pain related disability and quality of life.MethodsThe VERTOS IV study is a prospective, multicenter RCT with pain relief as primary endpoint. Patients with a painful osteoporotic VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent, are included and randomized for PV or a sham intervention. In total 180 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with a standard Visual Analogue Scale (VAS) score for pain and pain medication. Necessary additional therapies and complications are recorded.DiscussionThe VERTOS IV study is a methodologically sound RCT designed to assess pain relief after PV compared to a sham intervention in patients with an acute osteoporotic VCF selected on strict inclusion criteria.Trial registrationThis study is registered at ClinicalTrials.gov., NCT01200277.

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.

Influence of coil thickness on packing, re-opening and retreatment of intracranial aneurysms: a comparative study between two types of coils.

Abstract Objectives: To compare packing, re-opening and retreatment of intracranial aneurysms treated with two types of coils with different wire thickness and different shapes. Materials and methods: Packing, defined as the ratio between volume of inserted coils and volume of aneurysm, was calculated for 235 aneurysms—120 treated with predominantly helical-shaped coils of 0.010-inch diameter wire (GDC 10) and 115 treated with predominantly complex shaped coils of 0.012-inch diameter wire (Cordis TruFill). Aneurysm packing, re-opening and retreatment during follow-up were compared for aneurysms treated with either type of coils. Results: Mean packing was significantly higher (absolute value 6.8%, relative value 23.0%, p < 0.0001) in aneurysms treated with Cordis TruFill coils compared with aneurysms coiled with GDC 10 coils. Six month follow-up angiography was available in 194 of 235 aneurysms. Re-opening occurred in 22 of 99 aneurysms (22.2%) treated with GDC 10 coils and in 15 of 95 aneurysms (15.8%) treated with Cordis TruFill coils. Retreatment was performed in 16 of 120 aneurysms (13.3%) treated with GDC 10 coils and in nine of 115 aneurysms (7.8%) treated with Cordis TruFill coils. Conclusion: Coiling of intracranial aneurysms using complex shaped Cordis TruFill coils with a wire diameter of 0.012 inch results in significantly better packing compared with helical GDC 10 coils of 0.010-inch diameter wire. The retreatment rate was lower for aneurysms treated with Cordis TruFill coils compared with aneurysms treated with GDC 10 coils.

The Prognostic Value of CT Angiography and CT Perfusion in Acute Ischemic Stroke.

Background: CT angiography (CTA) and CT perfusion (CTP) are important diagnostic tools in acute ischemic stroke. We investigated the prognostic value of CTA and CTP for clinical outcome and determined whether they have additional prognostic value over patient characteristics and non-contrast CT (NCCT). Methods: We included 1,374 patients with suspected acute ischemic stroke in the prospective multicenter Dutch acute stroke study. Sixty percent of the cohort was used for deriving the predictors and the remaining 40% for validating them. We calculated the predictive values of CTA and CTP predictors for poor clinical outcome (modified Rankin Scale score 3-6). Associations between CTA and CTP predictors and poor clinical outcome were assessed with odds ratios (OR). Multivariable logistic regression models were developed based on patient characteristics and NCCT predictors, and subsequently CTA and CTP predictors were added. The increase in area under the curve (AUC) value was determined to assess the additional prognostic value of CTA and CTP. Model validation was performed by assessing discrimination and calibration. Results: Poor outcome occurred in 501 patients (36.5%). Each of the evaluated CTA measures strongly predicted outcome in univariable analyses: the positive predictive value (PPV) was 59% for Alberta Stroke Program Early CT Score (ASPECTS) ≤7 on CTA source images (OR 3.3; 95% CI 2.3-4.8), 63% for presence of a proximal intracranial occlusion (OR 5.1; 95% CI 3.7-7.1), 66% for poor leptomeningeal collaterals (OR 4.3; 95% CI 2.8-6.6), and 58% for a >70% carotid or vertebrobasilar stenosis/occlusion (OR 3.2; 95% CI 2.2-4.6). The same applied to the CTP measures, as the PPVs were 65% for ASPECTS ≤7 on cerebral blood volume maps (OR 5.1; 95% CI 3.7-7.2) and 53% for ASPECTS ≤7 on mean transit time maps (OR 3.9; 95% CI 2.9-5.3). The prognostic model based on patient characteristics and NCCT measures was highly predictive for poor clinical outcome (AUC 0.84; 95% CI 0.81-0.86). Adding CTA and CTP predictors to this model did not improve the predictive value (AUC 0.85; 95% CI 0.83-0.88). In the validation cohort, the AUC values were 0.78 (95% CI 0.73-0.82) and 0.79 (95% CI 0.75-0.83), respectively. Calibration of the models was satisfactory. Conclusions: In patients with suspected acute ischemic stroke, admission CTA and CTP parameters are strong predictors of poor outcome and can be used to predict long-term clinical outcome. In multivariable prediction models, however, their additional prognostic value over patient characteristics and NCCT is limited in an unselected stroke population.