Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.

Extramedullary Cavernous Hemangioma with Intradural and Extradural Growth and Clinical Symptoms of Brown-Séquard Syndrome: Case Report and Review of the Literature.

BACKGROUND: Primary spinal tumors are rare. Symptoms depend on the size and location of the tumor. CASE DESCRIPTION: A patient presented with a rare clinical finding, Brown-Séquard syndrome. The symptoms were caused by an extramedullary tumor compressing on the thoracic spinal cord. Pathologic examination showed cavernous hemangioma with growth both intradurally and extradurally. CONCLUSIONS: This is an extremely rare finding; to our knowledge, only 1 case report has been published before in which a spinal cavernous hemangioma had intradural and extradural growth. The clinical symptoms of Brown-Séquard syndrome have not been described before in the findings of spinal cavernous hemangiomas.

Late-life brain volume: a life-course approach. The AGES-Reykjavik study.

The "fetal-origins-of-adult-disease" hypothesis proposes that an unfavorable intrauterine environment, estimated from small birth size, may induce permanent changes in fetal organs, including the brain. These changes in combination with effects of (cardiovascular) exposures during adult life may condition the later risk of brain atrophy. We investigated the combined effect of small birth size and mid-life cardiovascular risk on late-life brain volumes. Archived birth records of weight and height were abstracted for 1348 participants of the age, gene/environment susceptibility-Reykjavik study (RS; 2002-2006) population-based cohort, who participated in the original cohort of the RS (baseline 1967). Mid-life cardiovascular risk factors (CVRF) were collected in the RS. As a part of the late-life age, gene/environment susceptibility-RS examination, a brain magnetic resonance imaging was acquired and from it, volumes of total brain, gray matter, white matter, and white matter lesions were estimated. Adjusting for intracranial volume, demographics, and education showed small birth size (low ponderal index [PI]) and increased mid-life cardiovascular risk had an additive effect on having smaller late-life brain volumes. Compared with the reference group (high PI/absence of mid-life CVRF), participants with lower PI/presence of mid-life CVRF (body mass index >25 kg/m(2), hypertension, diabetes, "ever smokers") had smaller total brain volume later in life; B (95% confidence interval) were -10.9 mL (-21.0 to -0.9), -10.9 mL (-20.4 to -1.4), -20.9 mL (-46.9 to 5.2), and -10.8 mL (-19.3 to -2.2), respectively. These results suggest that exposure to an unfavorable intrauterine environment contributes to the trajectory toward smaller brain volume, adding to the atrophy that may be associated with mid-life cardiovascular risk.

[Spontaneus intracerebral haemhorrhage--review]. / Sjálfsprottin heilavefsblæding--yfirlitsgrein.

Spontaneous intracerebral hemorrhage occurs when a blood vessel within the brain parenchyma ruptures without a near related trauma. It is the second most common form of stroke, accounting for approximately 10% to 15% of new strokes. The 30 day mortality is very high (25-50%). Hypertension is the most common cause. Unfortunately, surgery has not proven to be helpful except in certain exceptions such as in large cerebellar hemorrhage. Nonetheless, it is very important that patients with ICH are admitted to an intensive care or a stroke unit with close surveillance of consciousness, focal neurologic symptoms, blood pressure and fluid balance.

[Spontaneous subarachnoid haemorrhage--review]. / Sjálfsprottin innanskúmsblæding--yfirlitsgrein.

Spontaneous subarachnoid hemorrhage is a bleeding in to the subarachnoid space without trauma. Aneurysms are the underlying cause in 80% of the cases. Among other causes are: arteriovenous malformations, anticoagulation, vasculitis or brain tumor. Spontaneous subarachnoid hemorrhage is a serious disease, where up to half of the patients die. Of those who survive, only half return to work and many have a reduced quality of life. To prevent rebleeding the aneurysm is closed either with endovascular coiling or neurosurgical clipping.

Coronary artery calcium, brain function and structure: the AGES-Reykjavik Study.

BACKGROUND AND PURPOSE: Several cardiovascular risk factors are associated with cognitive disorders in older persons. Little is known about the association of the burden of coronary atherosclerosis with brain structure and function. METHODS: This is a cross-sectional analysis of data from the Age, Gene, Environment Susceptibility (AGES)-Reykjavik Study cohort of men and women born 1907 to 1935. Coronary artery calcification (CAC), a marker of atherosclerotic burden, was measured with CT. Memory, speed of processing, and executive function composites were calculated from a cognitive test battery. Dementia was assessed in a multistep procedure and diagnosed according to international guidelines. Quantitative data on total intracranial and tissue volumes (total, gray matter volume, white matter volume, and white matter lesion volume), cerebral infarcts, and cerebral microbleeds were obtained with brain MRI. The association of CAC with dementia (n=165 cases) and cognitive function in nondemented subjects (n=4085), and separately with MRI outcomes, was examined in multivariate models adjusting for demographic and vascular risk factors. Analyses tested whether brain structure mediated the associations of CAC to cognitive function. RESULTS: Subjects with higher CAC were more likely to have dementia and lower cognitive scores, more likely to have lower white matter volume, gray matter volume, and total brain tissue, and to have more cerebral infarcts, cerebral microbleeds, and white matter lesions. The relations of cognitive performance and dementia to CAC were significantly attenuated when the models were adjusted for brain lesions and volumes. CONCLUSIONS: In a population-based sample, increasing atherosclerotic load assessed by CAC is associated with poorer cognitive performance and dementia, and these relations are mediated by evidence of brain pathology.

[A 49 year old male with a giant pulmonary bulla--a case report and review of the literature]. / Midaldra reykingamadur med risablödru í lunga--sjúkratilfelli.

A 49 year old previously healthy smoker was diagnosed with a giant bulla in his right lung, following a history of dry cough, repeated upper airway infections and increasing dyspnea for several years. Computed tomography (CT) confirmed the presence of a giant bulla in the right inferior lobe and several smaller bullae in the right superior lobe. The giant bulla was 17 cm in diameter, occupying more than half of the right hemithorax. On spirometry a moderate restrictive and a mild obstructive pattern was observed. Lung volume was measured with two different techniques, nitrogen washout and plethysmography, with volume of the bullae estimated at 2.9 L, similar to the 3.2 L determined by CT. The patient underwent thoracotomy, where the giant bulla together with the inferior lobe were removed with lobectomy and the small bullae in the superior lobe with wedge resection. Five months postoperatively the patient is in good health and is back at work. Postoperatively significant improvements in spirometry values and lung volume measurements have been documented. This case demonstrates that giant bullae can be successfully managed with surgical resection and their size can be determined by different techniques, including lung volume measurements and chest CT.

Subclinical intestinal inflammation and sacroiliac changes in relatives of patients with ankylosing spondylitis.

BACKGROUND & AIMS: It has been suggested that subclinical intestinal inflammation plays a pathogenic role in the spondylarthropathy of ankylosing spondylitis (AS). We assessed the possible presence and inheritance pattern of subclinical intestinal inflammation in first-degree relatives of patients with AS. The relationship between this inflammation and the subjects' HLA-B27 genotype as well as computerized tomographic sacroiliac abnormalities was also assessed. METHODS: A total of 124 of 213 (58%) available first-degree relatives of 47 patients with AS in Iceland underwent investigation for intestinal inflammation (fecal calprotectin concentration), HLA-B27 genotyping, and computerized tomography of the sacroiliac joints. RESULTS: A total of 41% of the first-degree relatives had subclinical intestinal inflammation, whereas 15 of 17 spouses were normal. Variance components analyses suggest that the inheritance pattern of this inflammation is affected by a major additive gene. Some sacroiliac changes, suggestive of early AS, differed significantly between subjects with and without subclinical intestinal inflammation (mean diameter of subchondral cysts [2.9 vs. 1.2 mm; P = 0.026] and blurring of joint margins [9 of 44 (20%) vs. 1 of 41 (2%); P = 0.02]). Intestinal inflammation and sacroiliac changes did not relate to the subjects' HLA-B27 status. CONCLUSIONS: Many first-degree relatives of patients with AS appear to have an inherited abnormality that leads to subclinical intestinal inflammation. The association between the presence of this inflammation and the sacroiliac changes suggests that it may play a pathogenic role in the spondylarthropathy of AS.