Categories
Vasculopathy

Are antiplatelets and anticoagulants safe and beneficial in people with cavernomas?

Long-term antithrombotic therapy and risk of intracranial haemorrhage from cerebral cavernous malformations: a population-based cohort study, systematic review, and meta-analysis.

Zuurbier SM, Hickman CR, Tolias CS, et al; Scottish Audit of Intracranial Vascular Malformations Steering Committee.

Lancet Neurol 2019; 18:935-941.

Abstract

BACKGROUND:

Antithrombotic (anticoagulant or antiplatelet) therapy is withheld from some patients with cerebral cavernous malformations, because of uncertainty around the safety of these drugs in such patients. We aimed to establish whether antithrombotic therapy is associated with an increased risk of intracranial haemorrhage in adults with cerebral cavernous malformations.

METHODS:

In this population-based, cohort study, we used data from the Scottish Audit of Intracranial Vascular Malformations, which prospectively identified individuals aged 16 years and older living in Scotland who were first diagnosed with a cerebral cavernous malformation during 1999-2003 or 2006-10. We compared the association between use of antithrombotic therapy after first presentation and the occurrence of intracranial haemorrhage or persistent or progressive focal neurological deficit due to the cerebral cavernous malformations during up to 15 years of prospective follow-up with multivariable Cox proportional hazards regression assessed in all individuals identified in the database. We also did a systematic review and meta-analysis, in which we searched Ovid MEDLINE and Embase from database inception to Feb 1, 2019, to identify comparative studies to calculate the intracranial haemorrhage incidence rate ratio according to antithrombotic therapy use. We then generated a pooled estimate using the inverse variance method and a random effects model.

FINDINGS:

We assessed 300 of 306 individuals with a cerebral cavernous malformation who were eligible for study. 61 used antithrombotic therapy (ten [16%] of 61 used anticoagulation) for a mean duration of 7·4 years (SD 5·4) during follow-up. Antithrombotic therapy use was associated with a lower risk of subsequent intracranial haemorrhage or focal neurological deficit (one [2%] of 61 vs 29 [12%] of 239, adjusted hazard ratio [HR] 0·12, 95% CI 0·02-0·88; p=0·037). In a meta-analysis of six cohort studies including 1342 patients, antithrombotic therapy use was associated with a lower risk of intracranial haemorrhage (eight [3%] of 253 vs 152 [14%] of 1089; incidence rate ratio 0·25, 95% CI 0·13-0·51; p<0·0001; I2=0%).

INTERPRETATION:

Antithrombotic therapy use is associated with a lower risk of intracranial haemorrhage or focal neurological deficit from cerebral cavernous malformations than avoidance of antithrombotic therapy. These findings provide reassurance about safety for clinical practice and require further investigation in a randomised controlled trial.

 

See also

Bervini D, Jaeggi C, Mordasini P, Schucht P, Raabe A. Antithrombotic medication and bleeding risk in patients with cerebral cavernous malformations: a cohort study. J Neurosurg 2018; doi: 10.3171/2018.1.JNS172547 (Epub ahead of print).

Both papers are cited in the neurochecklist:

Cerebral cavernous malformations (cavernomas): clinical features

Abstract link 1

Abstract link 2

By Karlo J Lizarraga and Antonio AF De Salles – https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-469, CC BY 2.5, Link
Categories
Vasculopathy

How does aspirin influence the rupture risk of cerebral aneurysms?

Association between aspirin dose and subarachnoid hemorrhage from saccular aneurysms: a case-control study.

Neurology 2018; 91:e1175-e1181.

Can A, Rudy RF, Castro VM, et al.

Abstract

OBJECTIVE:

To determine the association between ruptured saccular aneurysms and aspirin use/aspirin dose.

METHODS:

Four thousand seven hundred one patients who were diagnosed at the Massachusetts General Hospital and Brigham and Women’s Hospital between 1990 and 2016 with 6,411 unruptured and ruptured saccular intracranial aneurysms were evaluated. Univariable and multivariable logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and aspirin use, including aspirin dose. Inverse probability weighting using propensity scores was used to adjust for potential differences in baseline characteristics between cases and controls. Additional analyses were performed to examine the association of aspirin use and rerupture before treatment.

RESULTS:

In multivariate analysis with propensity score weighting, aspirin use (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.45-0.80) was significantly associated with decreased risk of ruptured intracranial aneurysms. There was a significant inverse dose-response relationship between aspirin dose and aneurysmal subarachnoid hemorrhage (OR 0.65, 95% CI 0.53-0.81). In contrast, there was a significant association between aspirin use and increased risk of rerupture before treatment (OR 8.15, 95% CI 2.22-30.0).

CONCLUSIONS:

In this large case-control study, aspirin therapy at diagnosis was associated with a significantly decreased risk of subarachnoid hemorrhage, with an inverse dose-response relationship among aspirin users. However, once rupture has occurred, aspirin is associated with an increased risk of rerupture before treatment.

This paper is cited in the neurochecklist:

Cerebral aneurysms: risk factors for rupture

Abstract link

By Tiago Etiene QueirozOwn work, CC BY-SA 3.0, Link
Categories
Vasculopathy

How often does cervical artery dissection recur?

Recurrence of cervical artery dissection: an underestimated risk

Kloss M, Grond-Ginsbach C, Ringleb P, Hausser I, Hacke W, Brandt T.

Neurology 2018; 90:e1372-e1378.

Abstract

OBJECTIVE:

To explore the recurrence of cervical artery dissection (CeAD).

METHODS:

A single-center consecutive series of 282 CeAD patients was prospectively recruited during first admission from 1995 to 2012. Patients with a follow-up of at least 1 year (n = 238) were eligible for the current analysis. All patients with clinical symptoms or signs of recurrent CeAD on ultrasound were examined by MRI. Dermal connective tissue morphology was studied in 108 (45.4%) patients.

RESULTS:

Median follow-up was 52 months (range 12-204 months). In all, 221 (92.8%) patients presented with monophasic CeAD, including 188 (79.0%) patients with a single CeAD event, 11 (4.6%) with simultaneous dissections in multiple cervical arteries, and 22 (9.2%) with subsequent events within a single phase of 4 weeks. Seventeen patients (7.1%) had late (>1 month after the initial event) recurrent CeAD events, including 5 (2.1%) with multiple recurrences. Patients with late recurrences were younger (37.5 ± 6.9 years) than those without (43.8 ± 9.9; p = 0.011). Ischemic stroke occurred in 164 (68.9%) patients at first diagnosis, but only 4 of 46 (8.7%) subsequent events caused stroke (p < 0.0001), while 19 (41.3%) were asymptomatic. Connective tissue abnormalities were found in 54 (56.3%) patients with monophasic and 8 (66.7%) with late recurrent dissections (p = 0.494).

CONCLUSION:

Twenty-two (9.2%) patients had new cerebral artery dissection events within 1 month and 17 (7.1%) later recurrences. The risk for new events was significantly higher (about 60-fold) during the acute phase than during later follow-up. Connective tissue abnormalities were not more frequent in patients with late recurrent events than in those with monophasic CeAD.

This article is now cited in the neurochecklist:

Cervical artery dissection (CAD): clinical features

Abstract link 1

By Henry Vandyke CarterHenry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 513, Public Domain, Link
Categories
Vasculopathy

What factors predict bleeding from cerebral amyloid angiopathy?

The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study.

Rodrigues MA, Samarasekera N, Lerpiniere C, et al.

Lancet Neurol 2018; 17:232-240.

Abstract

BACKGROUND:

Identification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype.

METHODS:

We identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy.

FINDINGS:

Among 110 adults (median age 83 years [IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86-0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88-100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78-100).

INTERPRETATION:

The CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.

This article is now cited in the neurochecklist:

Cerebral amyloid angiopathy (CAA): clinical features

Abstract link

Oxygen pathways in the brain. Viktor Brezinsky on Flickr. https://www.flickr.com/photos/82295498@N07/8100351180
Categories
Vasculopathy

Do lipid lowering drugs reduce the risk of intracranial aneurysm rupture?

Lipid-lowering agents and high HDL (high-density lipoprotein) are inversely associated with intracranial aneurysm rupture

Stroke 2018; Epub ahead of print

Can A, Castro VM, Dligach D, et al.

 

Abstract

Background:

Growing evidence from experimental animal models and clinical studies suggests the protective effect of statin use against rupture of intracranial aneurysms; however, results from large studies detailing the relationship between intracranial aneurysm rupture and total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and lipid-lowering agent use are lacking.

Methods:

The medical records of 4701 patients with 6411 intracranial aneurysms diagnosed at the Massachusetts General Hospital and the Brigham and Women’s Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the effects of lipids (total cholesterol, LDL, and HDL) and lipid-lowering medications on intracranial aneurysm rupture risk. Propensity score weighting was used to account for differences in baseline characteristics of the cohorts.

Results:

Lipid-lowering agent use was significantly inversely associated with rupture status (odds ratio, 0.58; 95% confidence interval, 0.47-0.71). In a subgroup analysis of complete cases that includes both lipid-lowering agent use and lipid values, higher HDL levels (odds ratio, 0.95; 95% confidence interval, 0.93-0.98) and lipid-lowering agent use (odds ratio, 0.41; 95% confidence interval, 0.23-0.73) were both significantly and inversely associated with rupture status, whereas total cholesterol and LDL levels were not significant. A monotonic exposure-response curve between HDL levels and risk of aneurysmal rupture was obtained.

Conclusions:

Higher HDL values and the use of lipid-lowering agents are significantly inversely associated with ruptured intracranial aneurysms.

This reference is cited in the Neurochecklist:

Cerebral aneurysms: risk factors for rupture

Abstract link

By Tiago Etiene QueirozOwn work, CC BY-SA 3.0, Link
Categories
Vasculopathy

What are the risk factors for multiple intracranial aneurysms?

Risk factors for and clinical consequences of multiple intracranial aneurysms: a systematic review and meta-analysis

Jabbarli R, Dinger TF, Darkwah Oppong M, et al.

Stroke 2018; (Epub ahead of print).

Abstract

BACKGROUND AND PURPOSE:

Multiple intracranial aneurysms (MIAs) are common findings of cerebral angiographies; however, MIA prevalence varies in different patient cohorts. We sought to elucidate risk factors influencing MIA prevalence and the clinical consequences.

METHODS:

We systematically searched PubMed, Scopus, Embase, and Cochrane Library databases for publications before January 15, 2017, reporting MIA prevalence and risk factors. We used random-effects meta-analysis and multivariate regression analysis to assess the impacts of individual, study, and population characteristics.

RESULTS:

We included 174 studies reporting on MIA (mean overall prevalence, 20.1%; range, 2%-44.9%) in 134 study populations with 86 989 intracranial aneurysm (IA) patients enrolled between 1950 and 2015. Studies from Europe and North America (P<0.001) and more recent enrolment years (P=0.046) were independently associated with higher MIA prevalence. In meta-analysis, MIA correlated with female sex (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.4-1.8), higher patient age (>40 years; OR, 1.6; 95% CI, 1.14-2.25), arterial hypertension (OR, 1.51; 95% CI, 1.17-1.94), smoking (OR, 1.89; 95% CI, 1.37-2.6) and familial IA (OR, 2.02; 95% CI, 1.47-2.77), and formation of de novo (OR, 3.92; 95% CI, 1.95-7.87) and growth of initial IA (OR, 3.47; 95% CI, 1.87-6.45). Risk of subarachnoid hemorrhage in MIA patients was higher only in longitudinal studies from Japan and Korea (OR, 2.08; 95% CI, 1.46-2.96).

CONCLUSIONS:

Female sex, higher age, arterial hypertension, smoking, and familial IA are major risk factors for multiple intracranial aneurysms. In addition, MIA patients are at risk for enhanced IA formation. Further studies are needed to evaluate rupture risk and the role of ethnicity, especially in the context of increased MIA identification with improved neurovascular imaging.

This reference is cited in the neurochecklist:

Cerebral aneurysms: risk factors for formation

 

Abstract link

By HellerhoffOwn work, CC BY-SA 3.0, Link
Categories
Vasculopathy

What is the role of PET scanning in cerebral amyloid angiopathy?

Amyloid-PET in sporadic cerebral amyloid angiopathy: a diagnostic accuracy meta-analysis

Charidimou A, Farid K, Baron JC.

Neurology 2017; 89:1490-1498.

Abstract

OBJECTIVE:

To perform a meta-analysis synthesizing evidence of the value and accuracy of amyloid-PET in diagnosing patients with sporadic cerebral amyloid angiopathy (CAA).

METHODS:

In a PubMed systematic literature search, we identified all case-control studies with extractable data relevant for the sensitivity and specificity of amyloid-PET positivity in symptomatic patients with CAA (cases) vs healthy participants or patients with spontaneous deep intracerebral hemorrhage (ICH) (control groups). Using a hierarchical (multilevel) logistic regression model, we calculated pooled diagnostic test accuracy.

RESULTS:

Seven studies, including 106 patients with CAA (>90% with probable CAA) and 151 controls, were eligible and included in the meta-analysis. The studies were of moderate to high quality and varied in several methodological aspects, including definition of PET-positive and PET-negative cases and relevant cutoffs. The sensitivity of amyloid-PET for CAA diagnosis ranged from 60% to 91% and the specificity from 56% to 90%. The overall pooled sensitivity was 79% (95% confidence interval [CI] 62-89) and specificity was 78% (95% CI 67-86) for CAA diagnosis. A predefined subgroup analysis of studies restricted to symptomatic patients presenting with lobar ICH CAA (n = 58 vs 86 controls) resulted in 79% sensitivity (95% CI 61-90%) and 84% specificity (95% CI 65-93%). In prespecified bivariate diagnostic accuracy meta-analysis of 2 studies using 18F-florbetapir-PET, the sensitivity for CAA-ICH diagnosis was 90% (95% CI 76-100%) and specificity was 88% (95% CI 74-100%).

CONCLUSIONS:

Amyloid-PET appears to have moderate to good diagnostic accuracy in differentiating patients with probable CAA from cognitively normal healthy controls or patients with deep ICH. Given that amyloid-PET labels both cerebrovascular and parenchymal amyloid, a negative scan might be useful to rule out CAA in the appropriate clinical setting.

This reference is cited in the neurochecklist:

Cerebral amyloid angiopathy (CAA): radiological features

Abstract link

Beta-Amyloid Plaques and Tau in the Brain. NIH Image gallery on Flickr. https://www.flickr.com/photos/nihgov/38686503251
Categories
Vasculopathy

What features distinguish subarachnoid haemorrhage in people with polycystic kidneys?

Polycystic kidney disease among 4,436 intracranial aneurysm patients from a defined population

Nurmonen HJ, Huttunen T, Huttunen J, et al.

Neurology 2017; 89:1852-1859.

Abstract

OBJECTIVE:

To define the association of autosomal dominant polycystic kidney disease (ADPKD) with the characteristics of aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (IA) disease.

METHODS:

We fused data from the Kuopio Intracranial Aneurysm database (n = 4,436 IA patients) and Finnish nationwide registries into a population-based series of 53 IA patients with ADPKD to compare the aneurysm- and patient-specific characteristics of IA disease in ADPKD and in the general IA population, and to identify risks for de novo IA formation.

RESULTS:

In total, there were 33 patients with ADPKD with aSAH and 20 patients with ADPKD with unruptured IAs. The median size of ruptured IAs in ADPKD was significantly smaller than in the general population (6.00 vs 8.00 mm) and the proportion of small ruptured IAs was significantly higher (31% vs 18%). Median age at aSAH was 42.8 years, 10 years younger than in the general IA population. Multiple IAs were present in 45% of patients with ADPKD compared to 28% in the general IA population. Cumulative risk of de novo IA formation was 1.3% per patient-year (vs 0.2% in the general IA population). Hazard for de novo aneurysm formation was significantly elevated in patients with ADPKD (Cox regression hazard ratio 7.7, 95% confidence interval 2.8-20; p < 0.0005).

CONCLUSIONS:

Subarachnoid hemorrhage occurs at younger age and from smaller intracranial aneuryms in patients with ADPKD and risk for de novo IAs is higher than in the general Eastern Finnish population. ADPKD should be considered as an indicator for long-term angiographic follow-up in patients with diagnosed IAs.

Cerebral aneurysms: risk factors for formation

Abstract link

By Tiago Etiene QueirozOwn work, CC BY-SA 3.0, Link
Categories
Vasculopathy

What factors predispose to recurrent cerebral vein thrombosis?

Venous thrombotic recurrence after cerebral venous thrombosis: a long-term follow-up study

Palazzo P, Agius P, Ingrand P, et al.

Stroke 2017; 48:321-326.

Abstract

BACKGROUND AND PURPOSE:

After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence.

METHODS:

Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation.

RESULTS:

One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1-247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with recurrence.

CONCLUSIONS:

In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.

This reference is cited in the neurochecklist:

Cerebral vein thrombosis (CVT): clinical features

Abstract link

By HellerhoffOwn work, CC BY-SA 3.0, Link