Background
Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated ...the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, “high risk” elderly populations, and healthy individuals in population-based studies.
Methods
Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations.
Results
We identified 31 cohorts (n = 20,368): 19 ischemic stroke/TIA (n = 7672), 4 memory clinic (n = 1957), 3 high risk elderly (n = 1458) and 5 population-based cohorts (n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58–2.89 and adj-HR: 2.09; 95% CI: 1.71–2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68–8.08 and adj-HR: 3.93; 95% CI: 2.71–5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24–1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00–1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity.
Conclusions
Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.
We investigated the factors associated with cerebrospinal fluid (CSF) flow artifacts on fluid-attenuated inversion recovery imaging in patients with carotid artery (CA) stenosis.
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.
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).
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.
Abstract 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
–
82 years) 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 17 months (IQR: 3
–
50 months), 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.
Microangiopathy associated with hypertension is a notable cause of cerebral small vessel disease (SVD), including deep intracerebral hemorrhage (ICH) and lacunar infarct. Dotlike low-intensity spots ...(dotlike hemosiderin spots: dotHSs) on T2*-weighted magnetic resonance (MR) images have been histologically diagnosed as old cerebral microbleeds associated with lipohyalinosis, amyloid angiopathy, or other microangiopathies and located in deep or subcortical regions. The aim of this study was to determine whether dotHSs indicate the severity of microangiopathy, and if so, whether large numbers of deep dotHSs are associated with SVD recurrence.
The authors prospectively analyzed the number of dotHSs in 337 patients-191 men and 146 women with a mean age of 66 +/- 10.4 years (range 37-94 years)-with SVD (199 ICHs and 138 lacunar infarcts) who had been consecutively admitted to Hakodate Municipal Hospital. The follow-up period was 3.5 to 42 months (22.5 +/- 13.1 months). Patients were divided into two groups based on the recurrence. The hazard ratio (HR) for recurrence was estimated based on the Cox proportional hazard model by using the number of deep and subcortical dotHSs as well as other factors. Of 337 patients, 20 were readmitted with recurrence. Results of a multivariate analysis revealed an elevated rate of recurrence in patients with many subcortical dotHSs (> or = 5, HR 4.36, p = 0.0019) or a history of ICH (HR 3.82, p = 0.014). A trend toward a positive correlation (Pearson correlation coefficient 0.548, p < 0.0001) was found between the number of deep and subcortical dotHSs.
Although a small sample size limited the power of analyses, the findings indicate that a large number of subcortical dotHSs may predict SVD recurrence.
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.
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.
Olfactory ensheathing cells (OECs) or Schwann cells were transplanted into the transected dorsal columns of the rat spinal cord to induce axonal regeneration. Electrophysiological recordings were ...obtained in an isolated spinal cord preparation. Without transplantation of cells, no impulse conduction was observed across the transection site; but following cell transplantation, impulse conduction was observed for over a centimeter beyond the lesion. Cell labelling indicated that the regenerated axons were derived from the appropriate neuronal source, and that donor cells migrated into the denervated host tract. As reported in previous studies, the number of regenerated axons was limited. Conduction velocity measurements and morphology indicated that the regenerated axons were myelinated, but conducted faster and had larger axon areas than normal axons. These results indicate that the regenerated spinal cord axons induced by cell transplantation provide a quantitatively limited but rapidly conducting new pathway across the transection site.
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.
Olfactory ensheathing cells (OECs), which have properties of both astrocytes and Schwann cells, can remyelinate axons with a Schwann cell-like pattern of myelin. In this study the pattern and extent ...of remyelination and the electrophysiological properties of dorsal column axons were characterized after transplantation of OECs into a demyelinated rat spinal cord lesion. Dorsal columns of adult rat spinal cords were demyelinated by x-ray irradiation and focal injections of ethidium bromide. Cell suspensions of acutely dissociated OECs from neonatal rats were injected into the lesion 6 d after x-ray irradiation. At 21-25 d after transplantation of OECs, the spinal cords were maintained in an in vitro recording chamber to study the conduction properties of the axons. The remyelinated axons displayed improved conduction velocity and frequency-response properties, and action potentials were conducted a greater distance into the lesion, suggesting that conduction block was overcome. Quantitative histological analysis revealed remyelinated axons near and remote from the cell injection site, indicating extensive migration of OECs within the lesion. These data support the conclusion that transplantation of neonatal OECs results in quantitatively extensive and functional remyelination of demyelinated dorsal column axons.
Here we describe transplantation of olfactory ensheathing cells (OECs) or Schwann cells derived from transgenic pigs expressing the human complement inhibitory protein, CD59 (hCD59), into transected ...dorsal column lesions of the spinal cord of the immunosuppressed rat to induce axonal regeneration. Non-transplanted lesion-controlled rats exhibited no impulse conduction across the transection site, whereas in animals receiving transgenic pig OECs or Schwann cells impulse conduction was restored across and beyond the lesion site for more than a centimeter. Cell labeling indicated that the donor cells migrated into the denervated host tract. Conduction velocity measurements showed that the regenerated axons conducted impulses faster than normal axons. By morphological analysis, the axons seemed thickly myelinated with a peripheral pattern of myelin expected from the donor cell type. These results indicate that xenotranplantation of myelin-forming cells from pigs genetically altered to reduce the hyperacute response in humans are able to induce elongative axonal regeneration and remyelination and restore impulse conduction across the transected spinal cord.
PDF
