Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation.

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76-4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04-1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023;94:61-74.

Association of Ultrasonography and MRI Findings with Stroke Recurrence: Differences Between Patients with Past Histories of Atherothrombotic Versus Lacunar Infarctions.

OBJECTIVE: This study investigated the association of MRI and ultrasonography findings with stroke recurrence in patients with past histories of atherothrombotic infarctions (ATIs) or lacunar infarctions (LIs). METHODS: We prospectively analyzed the incidence of stroke recurrence. Deep and lobar cerebral microbleeds (MBs), asymptomatic lacunae, asymptomatic intracerebral hemorrhages (ICHs), severe white matter lesions (WML), and intima-media thickness (IMT) were investigated on enrollment. Stroke recurrence rates were compared by using the log-rank test. The odds ratios for recurrent strokes were derived using multivariate logistic regression models, adjusted for risk factors. RESULTS: We evaluated the stroke recurrence rate in 362 ATI patients and 309 LI patients. The log-rank test and multivariate analyses revealed that the incidence of recurrent stroke was significantly higher in ATI patients with mean IMT greater than or equal to 1.1 mm, asymptomatic ICHs, or lobar MBs than in those without. The incidence was significantly higher in LI patients with asymptomatic ICHs, asymptomatic LIs, and severe WMLs than in those without. In ATI patients, those with strictly lobar MBs or mixed MBs (deep and lobar MBs) had significantly higher recurrence rates than those without MB. In LI patients, those with strictly deep MBs or mixed MBs had higher recurrence rates than those without MB, and the incidences of those with mixed MBs was larger than those with strictly deep MBs. CONCLUSIONS: There were differences between ATI and LI patients in terms of the association of MRI and ultrasonography findings, in particularly strictly lobar or deep MBs, with the incidence of stroke recurrence.

Contribution of Deep Microbleeds to Stroke Recurrence: Differences between Patients with Past Deep Intracerebral Hemorrhages and Lacunar Infarctions.

BACKGROUND: This study investigated the contribution of deep cerebral microbleeds (MBs) to stroke recurrences in patients with histories of deep intracerebral hemorrhages (ICHs) or lacunar infarctions (LIs). METHODS: We prospectively analyzed stroke recurrences in patients admitted to our hospital who were treated for deep ICHs or LIs between April 2004 and December 2011. The number of deep MBs was counted on admission. Stroke recurrence-free rate curves were generated with the Kaplan-Meier method using the log-rank test. The odds ratios (ORs) for recurrent strokes were derived using multivariate logistic regression models, based on deep MBs and risk factors. RESULTS: We evaluated magnetic resonance images or the recurrences of 231 deep-ICH patients (92 women, 68.0 ± 12.0 years old) and 309 LI patients (140 women, 70.7 ± 11.7 years old). The incidences of deep ICHs (1.5%/year) and LIs (2.1%/year) presenting as stroke recurrences were significantly larger in LI patients with deep MBs than in those without (.01 [P = .0001] and .08%/year [P = .005], respectively). However, there was no significant difference between deep-ICH patients with and without MBs in terms of incidence of recurrences. Multivariate analyses revealed that deep MBs independently and significantly elevated the rate of deep ICHs (OR, 19.0; P = .007) or LIs (OR, 3.62; P = .008) presenting as recurrences in LI patients, but not in deep-ICH patients, when adjusted for stroke risk factors. CONCLUSIONS: There may be differences between patients with deep ICHs and those with LIs in terms of the contribution of deep MBs to stroke recurrence.

The Severity of White Matter Lesions Possibly Influences Stroke Recurrence in Patients with Histories of Lacunar Infarctions.

BACKGROUND: To investigate the recurrent stroke types associated with white matter lesions (WMLs), we prospectively observed recurrences in patients with histories of lacunar infarctions (LIs). METHODS: We prospectively analyzed the types of stroke recurrences in 305 patients (138 women, 70.2 ± 11.7 years old) consecutively admitted to our hospital with LIs from April 2004 to December 2011. WMLs were graded using Fazekas' grades (Gr). Recurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. RESULTS: The follow-up period was 50.7 ± 32.8 (.25-114) months. During this period, 62 strokes recurred. The incidences of strokes (all types), LIs, and deep intracerebral hemorrhages (ICHs) presenting as recurrences in 112 patients with Gr 2-3 were 6.2, 2.0, and 1.5 %/year, respectively, values that were significantly greater than those seen in 79 patients with Gr 0 (2.1 [P = .0001], .6 [P = .014], and .5 %/year [P = .016], respectively), and in 114 patients with Gr 1 (2.8 [P = .003], .9 [P = .009], and .6 %/year [P = .043], respectively). There was no significant difference among Gr 0, 1, and 2-3 in incidences of recurrences presenting as lobar ICHs, atherothrombotic infarctions, or cardioembolic infarctions. Multivariate analyses demonstrated that Gr 2-3 significantly and independently elevated the rate of deep ICHs or LIs presenting as recurrences after adjustment for risk factors. CONCLUSIONS: The presence of high-grade WMLs elevated the rate of stroke recurrences presenting as LIs and deep ICHs, but not other types.

The severities of white matter lesions possibly influence the recurrences of several stroke types.

BACKGROUND: White matter lesions (WML) have been reported to be a surrogate marker of stroke occurrences. To investigate the recurrent stroke types associated with WML, we prospectively observed recurrences in stroke patients. METHODS: We prospectively analyzed the types of stroke recurrence in 807 patients (351 women, 69.8 ± 12.0 years old) consecutively admitted to our hospital with strokes from April 2004 to October 2009. WML were graded using Fazekas grades. Recurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. RESULTS: The follow-up period was 31.6 ± 22.2 (range .5-71) months. During this period, 111 strokes recurred. The incidence of all stroke recurrences in 223 patients with grades 2 and 3 was 6.0% per year, which was significantly higher than that seen in 287 patients with grade 0 (2.1% per year, P = .006) and 297 patients with grade 1 (4.3% per year, P < .0001). The incidences of intracerebral hemorrhages (ICHs), lacunar infarctions, and atherothrombotic infarctions in patients with grades 2 and 3 were 1.2, 1.4, and 2.4% per year, respectively, which were higher than those seen in patients with grade 0 (.3%, P = .004; .2%, P = .002; and .9% per year, P = .010) but not similar to those in patients with grade 1 (.9%, P = .180; .9%, P = .161; and 1.4% per year, P = .249). There was no significant difference among grades 0, 1, 2, and 3 in incidence of stroke recurrences presenting as cardioembolic infarctions. CONCLUSIONS: The presence of high-grade WML elevated the rate of stroke recurrences presenting as ICHs, lacunar infarctions, and atherothrombotic infarctions but not as cardioembolic infarctions.

Nascent lobar microbleeds and stroke recurrences.

BACKGROUND: Lobar microbleeds (MBs) are occasionally visible on gradient-echo T2*-weighted (T2*-w) magnetic resonance imagings (MRIs) in patients with deep intracerebral hemorrhages (ICHs). This study investigated the contribution of nascent lobar MBs to occurrences of deep ICHs. METHODS: We prospectively analyzed nascent lobar MBs in patients admitted to our hospital who were treated with index strokes between April 2004 and November 2009. Numbers of nascent lobar MBs were counted on T2*-w MRI scans around 1 year after index strokes and compared with previous MRIs on admission. Deep ICH occurrence-free rate curves were generated by the Kaplan-Meier method using the log-rank test. The odds ratio (OR) for deep ICH occurrence was derived from a multivariate logistic regression model using nascent lobar MBs and risk factors. RESULTS: We investigated MRIs (interscan interval: 14.6 ± 5.9 months) of 508 patients (207 women, 68.9 ± 11.5 years), with a follow-up period of 44.1 ± 15.4 months. Repeated T2*-w MRIs demonstrated 157 nascent lobar MBs in 62 of 508 patients. The occurrence rate of deep ICHs (1.9% per year) was significantly higher in patients with nascent lobar MBs than in those without (.5% per year, P = .012). Multivariate analyses revealed that the rate of nascent lobar MBs was significantly elevated in patients with deep ICH-type stroke recurrences (OR: 3.85, P = .020), adjusted by the presence of hypertension, diabetes mellitus, use of antithrombotic drugs, severity of white matter lesions, age, and gender. CONCLUSIONS: Though a cohort study limited the power of analyses, our findings suggested that lobar MBs might be associated with deep ICH.

Nascent deep microbleeds and stroke recurrences.

BACKGROUND: Cerebral microbleeds (MBs) on gradient echo T2*-weighted magnetic resonance imaging (MRI) scans are associated with the severity of cerebral microangiopathies. This study investigated the contributions of nascent deep MBs to stroke recurrence. METHODS: We prospectively analyzed nascent deep MBs in patients admitted to our hospital who were treated for index strokes between April 2004 and November 2009. The number of nascent deep MBs was counted on T2*-weighted MRI scans around 1 year after the index strokes, and compared to previous MRIs on admission. Stroke recurrence-free rate curves were generated using the Kaplan-Meier method using the log-rank test. The odds ratio for nascent deep MBs was derived using a multivariate logistic regression model that was based on recurrent strokes and other risk factors. RESULTS: We evaluated the MRIs (interval between MRIs 14.6 ± 5.9 months) of 508 patients (207 women; 68.9 ± 11.5 years), with a follow-up period of 44.1 ± 15.4 months. Repeated T2*-weighted MRI scans revealed 256 nascent deep MBs in 116 of 508 patients. The incidence of deep intracerebral hemorrhage was significantly greater in patients with nascent deep MBs than those without (2.0% vs 0.4% per year, respectively; P < .0001). Multivariate analyses revealed that the rate of nascent deep MBs was significantly elevated in patients whose stroke recurrences took the form of deep intracerebral hemorrhages (odds ratio 5.41; P = .007), when adjusted for hypertension, preexisting MBs, and other risk factors. CONCLUSIONS: Our findings suggested that nascent deep MBs might be associated with stroke recurrence, in particular with deep intracerebral hemorrhage.

Difficult 6F Guiding Sheath Removal Using the Transradial Artery Approach: A Case Report.

Objective: Recently, the use of the radial artery approach for neuroendovascular treatment has become more frequent. The main advantage of this approach is that there is a low complication risk. However, in the aforementioned case, the 6F guiding sheath proved difficult to remove from the radial artery. Case Presentation: A 60-year-old female patient presented with an unruptured basilar tip aneurysm, which we treated with coil embolization under general anesthesia. We performed paracentesis on the right radial artery and inserted a 6F Axcelguide. The radial artery is bifurcated at the brachial region. We guided the Axcelguide to the right subclavian artery and filled the aneurysm with a coil. After embolization, we attempted to remove the Axcelguide. However, we encountered extreme resistance, and removal proved difficult. We injected verapamil, isosorbide nitrate, nitroglycerin, and papaverine hydrochloride intra-arterially and subcutaneously into the forearm and then performed a brachial plexus block. Unfortunately, the situation remained unchanged. We attempted to slowly remove the catheter with the vascular mass remaining adhered to it. We transected the radial artery in the middle. We could not achieve hemostasis through manual compression and thus injected n-butyl-2-cyanoacrylate intra-arterially. Postoperatively, the patient experienced mild subcutaneous hematoma and pain. Conclusion: We consider reporting this case valuable because no previous studies have described similar difficulties in removing a 6F guiding sheath from the radial artery.

Sex Differences in Frequency, Severity, and Distribution of Cerebral Microbleeds.

Importance: Cerebral small vessel disease (SVD) is associated with various cerebrovascular outcomes, but data on sex differences in SVD are scarce. Objective: To investigate whether the frequency, severity, and distribution of cerebral microbleeds (CMB), other SVD markers on magnetic resonance imaging (MRI), and outcomes differ by sex. Design, Setting, and Participants: This cohort study used pooled individual patient data from the Microbleeds International Collaborative Network, including patients from 38 prospective cohort studies in 18 countries between 2000 and 2018, with clinical follow-up of at least 3 months (up to 5 years). Participants included patients with acute ischemic stroke or transient ischemic attack with available brain MRI. Data were analyzed from April to December 2023. Main Outcomes and Measures: Outcomes of interest were presence of CMB, lacunes, and severe white matter hyperintensities determined on MRI. Additionally, mortality, recurrent ischemic stroke, and intracranial hemorrhage during follow-up were assessed. Multivariable random-effects logistic regression models, Cox regression, and competing risk regression models were used to investigate sex differences in individual SVD markers, risk of recurrent cerebrovascular events, and death. Results: A total of 20 314 patients (mean [SD] age, 70.1 [12.7] years; 11 721 [57.7%] male) were included, of whom 5649 (27.8%) had CMB. CMB were more frequent in male patients, and this was consistent throughout different age groups, locations, and in multivariable models (female vs male adjusted odds ratio [aOR], 0.86; 95% CI, 0.80-0.92; P < .001). Female patients had fewer lacunes (aOR, 0.82; 95% CI, 0.74-0.90; P < .001) but a higher prevalence of severe white matter hyperintensities (aOR, 1.10; 95% CI, 1.01-1.20; P = .04) compared with male patients. A total of 2419 patients (11.9%) died during a median (IQR) follow-up of 1.4 (0.7-2.5) years. CMB presence was associated with a higher risk of mortality in female patients (hazard ratio, 1.15; 95% CI, 1.02-1.31), but not male patients (hazard ratio, 0.95; 95% CI, 0.84-1.07) (P for interaction = .01). A total of 1113 patients (5.5%) had recurrent ischemic stroke, and 189 patients (0.9%) had recurrent intracranial hemorrhage, with no sex differences. Conclusions and Relevance: This cohort study using pooled individual patient data found varying frequencies of individual SVD markers between female and male patients, indicating potential pathophysiological differences in manifestation and severity of SVD. Further research addressing differences in pathomechanisms and outcomes of SVD between female and male patients is required.

Antithrombotic drug uses and deep intracerebral hemorrhages in stroke patients with deep cerebral microbleeds.

BACKGROUND: It has been suggested that antiplatelet or anticoagulant drugs elevate the rate of intracerebral hemorrhage (ICH) in patients with cerebral microbleeds (MBs). To investigate the mechanism by which antiplatelet drugs or warfarin may contribute to deep ICH occurrences in patients with deep MBs, we prospectively analyzed deep ICH occurrences in 807 consecutive patients (351 females and 456 males; mean age ± standard deviation 69.8 ± 12.0 years) who were admitted to our hospital with strokes. METHODS: Occurrence-free rate curves were generated using the Kaplan-Meier method; deep ICH occurrence-free rates were compared using the log-rank test. The follow-up period was 0.5 to 71 months (mean ± standard deviation 31.6 ± 22.2 months). RESULTS: In patients with deep MBs, the rates (1.0%/year; 6 ICHs in 180 patients) of deep ICH occurrence associated with antiplatelet drugs were not significantly greater than that without the drugs (1.0%/year; 6 ICHs in 167 patients; P = .977). The incidence of deep ICHs associated with warfarin use was not significantly greater than that without warfarin use. CONCLUSIONS: Multivariate analysis revealed that the use of antiplatelet drugs or warfarin did not significantly influence the occurrence of deep ICH in patients with deep MBs. Antiplatelet drugs or warfarin did not significantly elevate the rate of deep ICHs in stroke patients with pre-existing deep MBs.

Cerebrospinal Fluid CSF Flow Artifacts are Associated with Brain Pulsation in Patients with Severe Carotid Artery Stenoses.

OBJECTIVE: We investigated the factors associated with cerebrospinal fluid (CSF) flow artifacts on fluid-attenuated inversion recovery imaging in patients with carotid artery (CA) stenosis. METHODS: Each CSF artifact grade was defined by comparing the highest intensity in a given region of interest (ROI) to those in reference ROIs, as follows: higher than the intensity of normal white matter in the centrum semiovale = 2 points; equal to or less than the white matter, and higher than CSF = 1 point; and equal to CSF = 0. CSF flow scores in eight sites were measured and added to the total score (0 -16). The prevalences of each finding, specifically white matter lesions, CA stenoses and brain atrophy, were compared using multivariate logistic regression models. RESULTS: We evaluated the findings in 54 patients with CA stenosis treated by CA stenting (CAS) and 200 adults with no history of neurological disorders (control group). Adjusted by stroke risk factors, a CSF flow score ≤ 11 was positively associated with CA stenosis, heart rate > 70 / min, and brain atrophy, and negatively with the female gender. The score was 12.8 ± 1.8 in the control group and 12.0 ± 2.0 in CA stenosis group after CAS, which was significantly higher than before CAS (10.4 ± 2.8, p<0.001). CONCLUSION: The CSF flow score was associated with female gender, brain atrophy, heart rate, and severe CA stenosis, and was found to be elevated after revascularization.

Asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery stenoses.

BACKGROUND AND PURPOSE: Small vessel diseases (SVDs) are often asymptomatic. However, SVDs significantly influence the prognosis in patients with large vessel diseases (LVDs). We investigated asymptomatic cerebral findings on 3-Tesla MRI in patients with severe carotid artery (CA) stenoses, compared to peoples without a past history of neurological disorders, including strokes. METHODS: We retrospectively analyzed the prevalences of various asymptomatic cerebral findings which were intracerebral hemorrhages (ICHs), cortical superficial siderosis, ventricular dilatation (Evans' index) and SVDs including cerebral microbleeds (CMBs), lacunar infarctions (LIs), deep white matter hyperintensities (WMHs), periventricular hyperintensities (PVHs). The prevalence of each finding was compared using multivariate logistic regression models with adjustment for stroke risk factors. RESULTS: We evaluated the findings in 54 patients with severe CA stenosis treated by stenting (CA stenosis group) and 200 adults with health screening tests of the brain and no past history of neurological disorders (control group). Multivariate analyses adjusted for age ≥ 65 years old, female gender, hypertension, hyperlipidemia, diabetes mellitus, alcohol consumption, and smoking index revealed that the prevalences of severe PVHs, severe deep WMHs, asymptomatic deep ICHs, and asymptomatic LIs were significantly higher in the CA stenosis group than the control group. However, there were no significant differences in the prevalences of CMBs, or the remaining asymptomatic findings described above. CONCLUSIONS: With pathological differences between SVD and LVD, asymptomatic SVDs except CMBs and deep ICHs often co-exists severe CA stenosis as a presentative LVD.

Usefulness of Preoperative Simulation Using a Stereolithographic 3D Printer in Cerebral Aneurysm Coil Embolization.

Objective: We present a preoperative simulation of cerebral aneurysm coil embolization using a hollow model of cerebral blood vessels created by a stereolithography (SLA) 3D printer. Case Presentation: The patient was a 66-year-old woman. During follow-up, coil embolization was planned for an expanding paraclinoid aneurysm. A hollow cerebral vascular model was created preoperatively using an SLA 3D printer. The catheter was malleable and inserted into the hollow model, which enabled the surgeons to confirm its movement, stability, and ease of insertion. In the surgical procedure, the catheter was easily inserted into the aneurysm without reshaping. The procedure was completed without stability problems. Conclusion: The use of a hollow model of cerebral blood vessels was useful as a preoperative simulation and improved the safety of the procedure.

Elongated Internal Carotid Arteries in Patients with Severe Carotid Artery Stenosis.

OBJECTIVE: This study aimed to investigate the risk factors and asymptomatic cerebrovascular diseases associated with elongated internal carotid arteries (ICAs) and the relationship between ICA elongation and severe carotid artery (CA) stenosis. METHODS: We evaluated risk factors for stroke and magnetic resonance imaging (MRI) findings in patients with severe CA stenosis compared with people without neurological disorders who underwent brain screening (controls). On magnetic resonance angiography (MRA) images, we measured the longest distance, defined as the ICA distance, from the most distant anterior wall of the cervical ICA at the site of bending or kinking to the line between the origin of the external CA and the anterior protrusion of the ICA near the petrosal bone. We retrospectively compared various asymptomatic findings, including cerebral microbleeds, lacunar infarctions, and deep white matter hyperintensities (WMHs), between participants with an ICA distance ≥ 1.2 cm vs. < 1.2 cm. The prevalence of findings and stroke risk factors were compared using multivariate logistic regression models. RESULTS: We evaluated 53 patients (70.0 ± 8.1 years old, nine female) with severe CA stenosis treated by CA stenting and 400 controls (63.0 ± 9.2 years old, 227 females). Multivariate analyses showed that ICA distance ≥ 1.2 cm was associated with age ≥ 65 years (odds ratio (OR) = 1.8, p < 0.01), severe deep WMHs (OR = 2.0, p = 0.02), and severe CA stenosis (OR = 0.17, p < 0.01). CONCLUSION: ICA elongation, measured by ICA distance, was positively associated with age and deep WMHs and negatively associated with severe CA stenosis.

Development of imaging-based risk scores for prediction of intracranial haemorrhage and ischaemic stroke in patients taking antithrombotic therapy after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.

BACKGROUND: Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS: We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS: Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

Cerebral microbleeds and white matter hyperintensities in cardioembolic stroke patients due to atrial fibrillation: single-centre longitudinal study.

Cerebral microbleeds (CMBs) are a potential predictor of future stroke risk with clinical relevance for antithrombotic treatments, especially in ischaemic stroke patients with atrial fibrillation. However, prospective data on CMBs and risk of stroke in this particular stroke population remain scarce. We therefore performed a single centre longitudinal study to investigate CMBs and white matter hyperintensities (WMH) and the risk of future stroke. Consecutive acute stroke patients, admitted during 2008-2012 for presumed cardioembolic stroke due to non-valvular atrial fibrillation with available follow-up for the occurrence of recurrent stroke were included in our study. The rate of future stroke between patients with vs. without CMBs and moderate to severe WMH at baseline MRI was compared in separate survival and multivariable Cox regression analyses. A total of 119 cardioembolic stroke patients (49% female, median age: 76; IQR: 68-82years) were included. CMBs were found at baseline in 26/119 (21.8%; 95% CI: 14.8-30.4%) patients. Moderate to severe WMH were present in 27/119 (22.7%; 95% CI: 15.5-31.3%) cases. During a median follow-up time of 17months (IQR: 3-50months), 17 of 119 patients experienced a symptomatic stroke: 14 patients had an ischaemic stoke and 3 had intracerebral haemorrhage. The overall incidence rate for ischaemic stroke and intracerebral haemorrhage was 4.2 (95% CI: 2.3-7.1) and 0.9 (95% CI: 0.5-2.6) per 1000 patient-year of follow-up respectively. In multivariable Cox regression analysis the hazard ratio for total CMB number and the risk of stroke during follow-up was 1.05 (95% CI: 0.99-1.11; p=0.137, per each additional CMB increase), after adjusting for CHAD2S. A similar regression analysis demonstrated that moderate to severe WMHs were independently associated with increased risk of symptomatic stroke at follow-up, after adjusting for CHAD2S (HR: 2.99; 95% CI: 1.01-8.30; p=0.036). Despite the small sample size, our study provides useful data to guide power calculations and likely effect sizes relevant for ongoing and future larger studies and clinical trials.

The difference in location between traumatic cerebral microbleeds and microangiopathic microbleeds associated with stroke.

BACKGROUND AND PURPOSE: Microbleeds (MBs) are low-intensity spots on gradient echo T2*-weighted MRI frequently associated with cerebral microangiopathies resulting in stroke. MBs can also be caused by cerebral axonal injuries. We compared the location of MBs associated with cerebral microangiopathies with those associated with trauma. METHODS: T2*-weighted MRI identified traumatic MBs (t-MBs) in 23 (6 females; 38.7 ± 25.8 years old) of the 312 patients with head trauma consecutively admitted to our hospital between March 2003 and March 2009. We prospectively examined for the presence of microangiopathic MBs (m-MBs) in the 131 patients (59 females; 65.2 ± 9.2 years old) admitted consecutively for stroke (May -December 2004) as controls. RESULTS: We identified a total of 145 t-MBs and 504 m-MBs. t-MBs were frequently located in the mid portion of the subcortical area of the cerebrum, above the corpus callosum in axial slices, and were absent from the basal ganglia. In contrast, m-MBs were frequently located within the basal ganglia or thalamus. CONCLUSION: There are substantial differences in locations of MB development in trauma patients in comparison to stroke patients.