Familial idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a late-onset surgically alleviated, progressive disease. We characterize a potential familial subgroup of iNPH in a nation-wide Finnish cohort of 375 shunt-operated iNPH-patients. The patients were questionnaired and phone-interviewed, whether they have relatives with either diagnosed iNPH or disease-related symptomatology. Then pedigrees of all families with more than one iNPH-case were drawn. Eighteen patients (4.8%) from 12 separate pedigrees had at least one shunt-operated relative whereas 42 patients (11%) had relatives with two or more triad symptoms. According to multivariate logistic regression analysis, familial iNPH-patients had up to 3-fold risk of clinical dementia compared to sporadic iNPH patients. This risk was independent from diagnosed Alzheimer's disease and APOE epsilon 4 genotype. This study describes a familial entity of iNPH offering a novel approach to discover the potential genetic characteristics of iNPH. Discovered pedigrees offer an intriguing opportunity to conduct longitudinal studies targeting potential preclinical signs of iNPH. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms An Individual Patient Data Meta-analysis

OBJECTIVE: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIA) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. METHODS: For this IPD meta-analysis we performed an Embase and Pubmed search for studies published up to December 1, 2020. We included studies that 1) had a prospective study design; 2) included 50 or more patients with UIA; 3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and 4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial versus sporadic UIA using a Cox proportional hazard regression model adjusted for the PHASES score and smoking. We performed two analyses: 1. only studies defining first-degree relatives as parents, children, and siblings and 2. all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. RESULTS: We pooled IPD from eight cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings and children in six cohorts (29% Dutch, 55% Finnish, 15% Japanese), totalling 2,297 patients (17% familial, 399 patients) with 3,089 UIA and 7,301 person-years follow-up. Rupture occurred in 10 familial patients (rupture rate: 0·89%/person-year; 95% CI:0·45-1·59) and 41 sporadic patients (0·66%/person-year; 95% CI:0·48-0·89); adjusted HR for familial patients 2·56 (95% CI: 1·18-5·56). After adding also the two cohorts excluding siblings as first-degree relatives resulting in 9,511 patients the adjusted HR was 1·44 (95% CI: 0·86-2·40). CONCLUSION: The risk of rupture of UIA is two and a half times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account

Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure

Peer reviewe

High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms

Peer reviewe

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background-Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results-We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]= 1.11; P=4.1 x 10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1 x 10(-3)). Conclusions-Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.Peer reviewe

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe

Imaging Classification and Treatment of Spontaneous Intracranial Fusiform and Dissecting Aneurysms

Non peer reviewe

Why Does the Health-Related Quality of Life in Idiopathic Normal-Pressure Hydrocephalus Fail to Improve Despite the Favorable Clinical Outcome?

OBJECTIVE: Occasionally, a favorable clinical diseasespecific outcome does not reflect into improved generic health-related quality of life (HRQoL) in patients with idiopathic normal-pressure hydrocephalus (iNPH) at 1 year after the installation of a cerebrospinal fluid shunt. Our aim was to identify factors causing this discrepancy. METHODS: The 1-year HRQoL outcomes of 141 patients with iNPH were evaluated with the generic 15D instrument, in which the minimum clinically important change/difference on the 0-1 scale has been estimated to be +/- 0.015.A 12-point iNPH grading scale (iNPHGS) was used as a clinical disease-specific outcome measure, in which a 1-point decrease is considered to be clinically important. We identified 29 (21%) patients with iNPH from our prospective study whose HRQoL deteriorated or remained the same despite of a favorable iNPHGS outcome. We analyzed this discrepancy using patients' clinical variables and characteristics. RESULTS: Multivariate binary logistic regression analysis indicated that a greater (worse) iNPHGS score at baseline (adjusted odds ratio [OR], 1.7; 95% confidence interval [CI] 1.3-2.3; P <0.001), comorbid chronic pulmonary disease (40% vs. 20%; adjusted OR 17.8; 95% CI 3.6-89.9; P <0.001), and any comorbid nonmetastatic tumor (62% vs. 17%; adjusted OR 11.5; 95% CI 1.5-85.3; P [0.017) predicted discrepancy between iNPHGS and 15D outcomes. - CONCLUSIONS: Frail patients suffering from certain preexisting comorbidities may not experience improvement in generic HRQoL despite of a favorable clinical diseasespecific response. Acknowledging the comorbidity burden of the patient may help clinicians and the patients to understand the conflict between patient-reported and clinical outcomes.Peer reviewe