Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. METHODS: We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients.Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. RESULTS: The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). CONCLUSION: We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision. Although generalizability of the model is limited due to the selected population in which it was developed, this model could eventually be used to support clinical decision making after external validation. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, Number ISRCTN49866681.

Withdrawal of statins and risk of subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. METHODS: We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. RESULTS: During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). CONCLUSIONS: Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.

Relationship Between Physical Frailty and Low-Grade Inflammation in Late-Life Depression.

OBJECTIVES: To determine whether physical frailty is associated with low-grade inflammation in older adults with depression, because late-life depression is associated with physical frailty and low-grade inflammation. DESIGN: Baseline data of a cohort study. SETTING: Primary care and specialized mental health care. PARTICIPANTS: Individuals aged 60 and older with depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria (N = 366). MEASUREMENTS: The physical frailty phenotype, defined as three out of five criteria (weight loss, weakness, exhaustion, slowness, low physical activity level), and three inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL)) were assessed. RESULTS: The physical frailty phenotype was not associated with inflammatory markers in linear regression models adjusted for sociodemographic characteristics, lifestyle characteristics, and somatic morbidity. Of the individual criteria, handgrip strength was associated with CRP (ß = -0.21, P = .002) and IL-6 (ß = -0.25, P < .001), and gait speed was associated with NGAL (ß = 0.15, P = .02). Principal component analysis identified two dimensions within the physical frailty phenotype: performance-based physical frailty (encompassing gait speed, handgrip strength, and low physical activity) and vitality-based physical frailty (encompassing weight loss and exhaustion). Only performance-based physical frailty was associated with higher levels of inflammatory markers (CRP: ß = 0.14, P = .03; IL-6: ß = 0.13, P = .06; NGAL: ß = 0.14, P = .03). CONCLUSION: The physical frailty phenotype is not a unidimensional construct in individuals with depression. Only performance-based physical frailty is associated with low-grade inflammation in late-life depression, which might point to a specific depressive subtype.

Quantification of intracranial aneurysm morphodynamics from ECG-gated CT angiography.

RATIONALE AND OBJECTIVES: Aneurysm morphodynamics is potentially relevant for assessing aneurysm rupture risk. A method is proposed for automated quantification and visualization of intracranial aneurysm morphodynamics from electrocardiogram (ECG)-gated computed tomography angiography (CTA) data. MATERIALS AND METHODS: A prospective study was performed in 19 aneurysms from 14 patients with diagnostic workup for recently discovered aneurysms (n = 15) or follow-up of untreated known aneurysms (n = 4). The study was approved by the Institutional Review Board of the hospital and written informed consent was obtained from each patient. An image postprocessing method was developed for quantifying aneurysm volume changes and visualizing local displacement of the aneurysmal wall over a heart cycle using multiphase ECG-gated (four-dimensional) CTA. Percentage volume changes over the heart cycle were determined for aneurysms, surrounding arteries, and the skull. RESULTS: Pulsation of the aneurysm and its surrounding vasculature during the heart cycle could be assessed from ECG-gated CTA data. The percentage aneurysmal volume change ranged from 3% to 18%. CONCLUSION: ECG-gated CTA can be used to study morphodynamics of intracranial aneurysms. The proposed image analysis method is capable of quantifying the volume changes and visualizing local displacement of the vascular structures over the cardiac cycle.

Intracranial aneurysm segmentation in 3D CT angiography: method and quantitative validation with and without prior noise filtering.

Intracranial aneurysm volume and shape are important factors for predicting rupture risk, for pre-surgical planning and for follow-up studies. To obtain these parameters, manual segmentation can be employed; however, this is a tedious procedure, which is prone to inter- and intra-observer variability. Therefore there is a need for an automated method, which is accurate, reproducible and reliable. This study aims to develop and validate an automated method for segmenting intracranial aneurysms in Computed Tomography Angiography (CTA) data. Also, it is investigated whether prior smoothing improves segmentation robustness and accuracy. The proposed segmentation method is implemented in the level set framework, more specifically Geodesic Active Surfaces, in which a surface is evolved to capture the aneurysmal wall via an energy minimization approach. The energy term is composed of three different image features, namely; intensity, gradient magnitude and intensity variance. The method requires minimal user interaction, i.e. a single seed point inside the aneurysm needs to be placed, based on which image intensity statistics of the aneurysm are derived and used in defining the energy term. The method has been evaluated on 15 aneurysms in 11 CTA data sets by comparing the results to manual segmentations performed by two expert radiologists. Evaluation measures were Similarity Index, Average Surface Distance and Volume Difference. The results show that the automated aneurysm segmentation method is reproducible, and performs in the range of inter-observer variability in terms of accuracy. Smoothing by nonlinear diffusion with appropriate parameter settings prior to segmentation, slightly improves segmentation accuracy.

Genome-wide association study of intracranial aneurysm identifies three new risk loci.

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with approximately 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 10(-22)). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Glioblastoma multiforme in the posterior cranial fossa in a patient with neurofibromatosis type I.

Patients with Neurofibromatosis type 1 (NF1) have an increased risk of developing neoplasms. The most common brain tumors, found in 15%-20% of NF1 patients, are hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. These tumors generally have a benign nature. NF1 patients are predisposed to a 5-fold increased incidence of high-grade astrocytomas, which are usually located in supratentorial regions of the brain. We present an NF1 patient who developed a high-grade astrocytoma in the posterior fossa and discuss possible pathophysiological mechanisms.