Intracranial aneurysms in patients with Kawasaki disease or thoracic aortic aneurysms

Saccular intracranial aneurysm (sIA) is the most common type of IAs and characterized by outpoching sac with a neck arising from the cerebral artery wall. Pathophysiology of IAs are still poorly understood. Fusiform IA is a focal circumferential dilatation of the cerebral artery and unlike sIAs, do not have aneurysm neck, which make their treatment more complex compared to sIAs. The primary goal in the study I and II were to evaluate if Kawasaki disease (KD) is associated with increased risk for IAs (I) and white matter hyperintensities (WMH) (II); in the study III if sIAs are related with increased risk for thoracic aortic aneurysms (TAA) or dilatations (TAD); and in the study IV was to evaluate outcomes of flow diverter stent (FD) treatment of the ruptured posterior circulation fusiform IAs. In the study (I and II) 40 adults with a history of KD in a childhood were screened with brain Magnetic Resonance Imaging and Angiography for IAs and brain WMHs. No IAs were found in KD patients, which is significantly under the prevalence of 10% (95% CI 0%-8.8%, p = 0.03) that is the recommended limit for IA screening. In the study (II), we found that Kawasaki disease is related with increased WMH burden compared to age- and sex-matched migraine controls. Our study suggests that KD is not associated with IAs, but instead is associated with increased WMH burden, indicating long-term cerebrovascular involvement of KD. In the study (III) we retrospectively reviewed 411 patients with sIAs and available imaging studies (computed tomography or magnetic resonance imaging) of all thoracic aortic segments for TADs and TAAs. The prevalence of TADs and TAAs were 18% and 8%. Rheumatic disease and alcohol abuse were significant risk factors for TADs/TAAs. Our results suggests that sIAs might be associated with increased risk for TAAs and TADs. In the study (IV) five patients with ruptured posterior circulation fusiform aneurysms and treated with a FD were reviewed rertrospectively. We found that FD is a feasible treatment option for ruptured fusiform posterior circulation IAs, with a high aneurysm occlusion rate (100% at 6-months) and 80% of patients had a good outcome. However, FD treatment carries a significant risk for complications and should be considered only when other treatment options are not available.Aivovaltimoaneurysmien yhteys Kawasakin tautiin ja rinta-aortan laajentumiin. Sakkulaarinen aivovaltimoaneurysma (sIA) on yleisin aivoaneurysmatyyppi. SIA on aivovaltimoiden seinämästä työntyvä paikallinen pullistuma, joka yhdistyy aivovaltimon seinämään kaulalla. Fusiforminen IA on aivovaltimon paikallinen laajentuma ja toisin kuin sIA:ssa, fusiformisessa IA:ssa ei ole erillistä kaulaa, joka tekee hoidosta haastavaa. IA:ien syntymisen patofysiologia tunnetaan huonosti. Tutkimuksien (I) ja (II) tavoitteena oli selvittää, onko lapsuuden Kawasakin taudilla yhteyttä suurentuneeseen riskiin vuotamattomille IA:lle ja aivojen valkean aineen muutoksille. Tutkimuksen (III) tavoitteena oli selvittää ovatko sIA:t yhteydessä suurentuneeseen riskiin torakaaliaortan aneurysmille (TAA) tai dilataatioille (TAD). Tutkimuksen (IV) tarkoituksena oli selvittää flow diverter stenttihoidon (FD) tuloksia vuotaneiden takaverenkierron fusiformisten IA:ien hoidossa. Tutkimuksissa (I ja II) 40:lle lapsuudessa Kawasakin taudin sairastaneelle potilaalle suoritettiin aivojen ja aivoverisuonten magneettikuvaus IA:ien ja WMH muutosten seulomiseksi. Valkean aineen muutosten määrää verrattiin ikä- ja sukupuolivakioituihin verrokkeihin (migreenipotilaat). Kawasakin taudin sairastaneilla potilailla ei todettu IA:a ja prevalenssi oli merkittävästi alle suositellun IA:en seulontarajan 10 % (95 % CI 0 %-8.8 %, p= 0.03). Sen sijaan Kawasakin taudin sairastaneilla henkilöillä oli merkittävästi enemmän valkean aineen muutoksia verrokkeihin nähden, viitaten siihen, että Kawasakin taudilla voi olla myös aivoverisuoniin kohdistuvia vaikutuksia. Tutkimuksessa (III) analysoimme retrospektiivisetsti 411 sIA potilasta, joilla oli kuvannettu rinta-aortta tietokonetomografialla tai magneettikuvauksella. TAD:n ja TAA:n prevalenssi oli 18 % ja 8 %. Reumasairaus ja alkoholin väärinkäyttö lisäsivät merkittävästi riskiä TAD:lle/TAA:lle. SIA:iin saattaa liittyä suurentunut riski TAD:lle/TAA:lle. Tutkimuksessa (IV) analysoimme retrospektiivisesti viisi potilasta, joiden vuotanut aivojen takaverenkierron fusiforminen IA oli hoidettu FD:llä. Aneurysmien hoitotulokset olivat hyviä FD:llä ja 80 % potilaista toipuivat hyvin. FD hoitoon liittyy kuitenkin merkittäviä komplikaatioriskejä ja FD hoitoa tulisi miettiä vuotaneissa aneurysmissa vain, jos muut hoitovaihtoehdot katsotaan mahdottomiksi

Aortic calcification index predicts mortality and cardiovascular events in operatively treated patients with peripheral artery disease: A prospective PURE ASO cohort follow-up study

Objective: The present study evaluates the association of aortic calcification with mortality and major adverse cardiovascular and leg events (MACEs and MALEs) in patients with peripheral artery disease (PAD). The risk for mortality and MACEs and MALEs is considered in clinical decision-making.Methods: This cohort found in 2012-2013 consists of 226 patients with symptomatic PAD referred to Turku University Hospital for invasive treatment. Follow-up data about mortality and survival without MACEs and MALEs were collected up to 5 years from the inclusion date, and aortic calcification index (ACI) was measured from patients with available imaging studies (164 of 226). ACIs' association with events and mortality was evaluated in Cox regression, Kaplan-Meier, and classification and regression tree analysis.Results: All-cause mortality at 1, 3, and 5 years was 13.7% (31), 26.1% (59), and 46.9% (106), respectively. In multivariable Cox regression analysis, ACI and ACI > 43 were independent risk factors for all-cause mortality (hazard ratio [HR]: 1.13 per 10 units, 95% confidence interval [CI]: 1.00-1.22 and HR: 1.83, 95% CI: 1.01-3.32, respectively) and for MACEs (HR: 1.10 per 10 units, 95% CI: 1.00-1.22 and HR: 3.14, 95% CI: 1.67-5.91, respectively), but not for MALEs. Classification and regression tree analysis showed that ACI = 43 best divides cohort in relation to mortality. Kaplan-Meier analyses showed that ACI > 43 is associated with greater mortality and occurrence of MACEs compared with those who have ACI ≤ 43 (log-rank P value .005 and .0012, respectively).Conclusions: Risk for mortality and MACEs is associated with high ACI. ACI can expose the risk in patients with PAD for further cardiovascular events and mortality.</p

Physical exertion as a risk factor for perimesencephalic nonaneurysmal subarachnoid hemorrhage

Background: Perimesencephalic and nonperimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-naSAH and NPM-naSAH) have a different bleeding pattern and clinical course. The etiology and risk factors for PM-naSAH and NPM-naSAH are unclear. The objective of this study was to compare risk factors and triggering events between PM-naSAH and NPM-naSAH.Methods: We reviewed retrospectively all patients (n = 3475) who had undergone cerebral digital subtraction angiography between 2003 and 2020 at our tertiary hospital. Of these, 119 patients had 6-vessel angiography negative subarachnoid hemorrhage (47 (39%) PM-naSAH and 72 (61%) NPM-naSAH) and accurate information about the triggering event was available in 42 (89%) PM-NASAH and 64 (89%) NPM-naSAH patients.Results: PM-naSAH were younger compared to NPM-naSAH (mean age [SD]; 55.3 [11.1] years vs. 59.6 [12.2] years, p = .045. PM-naSAH was triggered during the physical exertion in 79% of patients and 16% of patients with NPM-naSAH (relative risk 5.4; 95% CI, 2.9-10.1, p .05.Conclusion: Physical exertion was a triggering factor in most of the PM-naSAH cases and the risk was five times greater than in NMP-naSAH. More studies are needed to confirm our results and to study pathophysiology of PM-naSAH and NPM-naSAH.</p

Acute hormonal findings after aneurysmal subarachnoid hemorrhage - report from a single center

Purpose: The aim was to assess anterior pituitary hormone levels during the acute phase of aneurysmal subarachnoid hemorrhage (aSAH) and analyze the possible association with the clinical condition and outcome. Material and methods: Forty patients with aSAH whose aneurysm was secured by endovascular coiling were enrolled. Basal secretions of cortisol, testosterone, luteinizing hormone (LH), prolactin (PRL), and sex hormone binding globulin (SHBG) levels were measured up to 14 days after the incident. Results: The main finding was that hypocortisolism was rare whereas testosterone deficiency was common in male patients. Furthermore, various other hormone deviations were frequent and there was wide interindividual variability. We found no association between delayed cerebral ischemia (DCI), outcome of the patients or aneurysm location, and hormone abnormalities, while both Hunt & Hess and Fisher grade were associated with low PRL levels. Hunt & Hess 5 was associated with low PRL concentration when compared to grades 1 (OR = 4.81, 95% CI 1.15-20.14, p = 0.03), 3 (OR 7.73, 95% CI 1.33-45.01, p = 0.02), and 4 (OR = 6.86 95% CI 1.28-26.83, p = 0.02). Fisher grade 4 was associated with low PRL concentration when compared to grades 3 (OR 3.37, 95% CI 1.06-10.73, p = 0.03) and 2 (OR 9.71, 95% CI 1.22-77.10, p = 0.04). Conclusion: Deviations from normal and huge interindividual differences are common in hormone levels during the acute phase of aSAH. Routine assessment of anterior pituitary function in the acute phase of aSAH is not warranted. During the follow-up in the outpatient clinic, hormone concentrations were not measured, which would have brought a more long-term perspective into our findings.Peer reviewe

Intracranial aneurysm is predicted by abdominal aortic calcification index: A retrospective case-control study

Background and aimsPatients with intracranial aneurysms (IA) have excess mortality for cardiovascular diseases, but little is known on whether atherosclerotic manifestations and IA coexist. We investigated abdominal aortic calcification index (ACI) association with unruptured and ruptured IAs.MethodsThis retrospective case-control study reviews all tertiary centers patients (n = 24,660) who had undergone head computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) for any reason between January 2003 and May 2018. Patients (n = 2020) with unruptured or ruptured IAs were identified, and patients with available abdominal CT were included. IA patients were matched by sex and age to controls (available abdomen CT, no IAs) in ratio of 1:3. ACI was measured from abdomen CT scans and patient records were reviewed.Results1720 patients (216 ruptured IA (rIA), 246 unruptured IA (UIA) and 1258 control) were included. Mean age was 62.9 ± 11.9 years and 58.2% were female. ACI (OR 1.02 per increment, 95%CI 1.01–1.03) and ACI>3 (OR 5.77, 95%CI 3.29–10.11) increased risk for rIA compared to matched controls. UIA patients' ACI was significantly higher but ACI did not increase odds for UIA compared to matched controls. History of coronary artery disease was less frequent in rIA patients. There was no calcification in aorta in 8.8% rIA and 13.6% UIA patients (matched controls 25.7% and 22.6% respectively, p ConclusionsAortic calcification is greater in rIA and UIA patients than matched controls. ACI increases risk for rIAs.</p

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Imaging Outcomes of Emergency MRI in Patients with Suspected Cerebral Venous Sinus Thrombosis: A Retrospective Cohort Study

Cerebral venous sinus thrombosis (CVST) is a rare neurological emergency condition with non-specific symptoms. Imaging options to rule out CVST are computed tomography (CT) and magnetic resonance imaging (MRI). This study aimed to determine the imaging outcomes of emergency MRI as a first-line imaging method in patients with suspected CVST. In this retrospective cohort study, we analyzed emergency brain MRI referrals from a five-year period in a tertiary hospital for suspicion of CVST. We recorded patient characteristics, risk factors mentioned in the referrals, and imaging outcomes. Altogether 327 patients underwent emergency MRI on the grounds of suspected CVST. MRI showed evidence of CVST among five patients (1.5%). Imaging showed other clinically significant pathology in 15% of the patients and incidental findings in 5% of the patients. Despite clinical suspicion, the diagnostic yield of emergency MRI for CVST is low and similar to that previously reported for CT. MRI is an alternative imaging method devoid of ionizing radiation in patients with suspected CVST

Imaging Outcomes of Emergency MRI in Patients with Suspected Cerebral Venous Sinus Thrombosis : A Retrospective Cohort Study

Cerebral venous sinus thrombosis (CVST) is a rare neurological emergency condition with non-specific symptoms. Imaging options to rule out CVST are computed tomography (CT) and magnetic resonance imaging (MRI). This study aimed to determine the imaging outcomes of emergency MRI as a first-line imaging method in patients with suspected CVST. In this retrospective cohort study, we analyzed emergency brain MRI referrals from a five-year period in a tertiary hospital for suspicion of CVST. We recorded patient characteristics, risk factors mentioned in the referrals, and imaging outcomes. Altogether 327 patients underwent emergency MRI on the grounds of suspected CVST. MRI showed evidence of CVST among five patients (1.5%). Imaging showed other clinically significant pathology in 15% of the patients and incidental findings in 5% of the patients. Despite clinical suspicion, the diagnostic yield of emergency MRI for CVST is low and similar to that previously reported for CT. MRI is an alternative imaging method devoid of ionizing radiation in patients with suspected CVST.Peer reviewe

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol

Introduction Positron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored. Our objective is to investigate feasibility of PET imaging using 18F-FDG and 68Ga-DOTANOC tracers to evaluate arterial wall inflammation in UIA.Methods and analysis This PET imaging feasibility study will enrol patients scheduled for surgical treatment of UIA. The study subjects will undergo PET imaging of the intracranial arteries within 1 month before planned surgery. The imaging protocol includes 18F-FDG PET MRI, MRA with gadolinium enhancement, and 68Ga-DOTANOC PET CT. The study will also involve preoperative blood samples, intraoperative cerebrospinal fluid (CSF) samples, and aneurysm sac biopsy. Planned sample size is at least 18 patients. Primary outcome is uptake of 18F-FDG or 68Ga-DOTANOC in intracranial arterial aneurysms compared with contralateral normal vessel as maximum standardised uptake value or target-to-blood pool ratio and correlation of uptake of 18F-FDG or 68Ga-DOTANOC to aneurysm histological findings. Secondary outcomes include estimating the correlations between uptake of 18F-FDG or 68Ga-DOTANOC and histological findings with blood and CSF miRNA-levels, arterial wall enhancement in gadolinium enhanced MRA, aneurysm size and shape, smoking, hypertension, and location of the aneurysm.Ethics and dissemination This study is approved by the Human Research Ethics Committee of the Hospital District of Southwest Finland, Finnish Medicines Agency Fimea, and Turku University Hospital. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences.Trial registration number NCT0471550