Multiple Cerebral Microbleeds Research Articles

Lobar cerebral microbleeds associated with transient focal neurological symptoms followed by symptomatic intracerebral hemorrhage

Cerebral microbleeds (CMBs) are defined as all discrete round-shaped hypointense areas on T2*-weighted magnetic resonance images (MRIs) with a gradient-echo (GRE) sequence [11]. CMBs can be regarded as a marker of vessel wall disorders with a higher tendency for intracerebral hemorrhage (ICH) [11]. It has been suggested that microbleeds increase the risk of ICH following antithrombotic administration for acute ischemic stroke [9, 14], though this issue remains controversial. In addition, there have been few reports of symptomatic ICH that has occurred at the site of microbleeds in the literature [2, 13]. However, these lesions themselves have been considered asymptomatic. We present a case of CMBs presenting with transient neurologic symptoms that developed into subsequent ICH. A 65-year-old man with no previous neurological history visited our hospital because of incoherent speech and headache. He had a history of diabetes mellitus and chronic hepatitis B. He had been diagnosed with hepatocellular carcinoma prior to this presentation. Neurological examination revealed that he had language disturbances with jargon speech and abnormal comprehension. These symptoms fluctuated and persisted for about half an hour after symptom onset. The results of other physical examinations were normal. Electroencephalography showed that there were no epileptiform discharges or abnormal inherent rhythms. There were also no acute ischemic brain lesions or hemorrhages on initial brain MRI (Fig. 1a). GRE images showed multiple CMBs in the left temporo-parieto-occipital lobe relevant to language disturbance (Fig. 1b). However, there were no CMBs in the deep subcortical area and brainstem. There were no CMBs on previous GRE images obtained at a local clinic 1 month prior to this presentation as well (Supplemental Figure). While he had no symptoms at this time, he underwent brain MRI as part of a medical check-up. All laboratory tests, including coagulation profiles, were normal. He was tentatively diagnosed with (1) recurrent transient ischemic attacks and (2) mood disorder associated with medical condition. During admission, he was treated with antihypertensive agents and 100 mg of aspirin for prevention of secondary ischemic stroke. On the fourth day of admission, he suddenly developed global aphasia and right hemiparesis. Follow-up GRE images showed a large lobar hematoma with perilesional edema in the left temporo-parietal lobe where the CMBs were previously seen (Fig. 1c). Although he was referred to the Department of Neurosurgery for surgical management, he was discharged with a modified Rankin scale of 5. Our case illustrates that localized CMBs can be related to transient neurological symptoms and subsequent ICH. Although this is a single case that represents a causal relationship between CMBs and transient neurological symptoms, the association between CMBs and subsequent ICH could not be clarified, suggesting that transient Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6504-8) contains supplementary material, which is available to authorized users.

Risk of Intracerebral Hemorrhage in Patients With Cerebral Microbleeds Undergoing Endovascular Intervention

Cerebral microbleeds (CMBs) on MRI gradient echo images are hemosiderin deposits, which may predict intracerebral hemorrhage (ICH). The risk of ICH in patients with CMBs could be exacerbated by the use of antithrombotics. The purpose of our study is to prospectively evaluate the risk of ICH in patients with ischemic stroke who receive dual antiplatelet therapy for endovascular intervention. We analyzed MRI of 133 patients admitted consecutively for intra- and extracranial stenting for symptomatic large artery atherosclerosis who received aspirin and clopidogrel. Quantity and location of CMBs were recorded by neuroradiologists independent from the angioplasty team. The primary end point was symptomatic ICH as evident in CT of the brain within 12 weeks of procedure. CMBs were identified in 23 patients. Mean number of CMBs was 2.3 ± 1.6. Four patients had >5 CMBs. Forty-seven patients had intracranial stents, 84 patients had extracranial stents, and 2 patients had both intracranial and extracranial stents. There was no difference in risk of symptomatic ICH between those with (4.3%) and without CMBs (5.5%) patient with CMBs (P=1.000). The presence of a small number of CMBs does not cause a large increase in the short-term risk of symptomatic ICH in patients with ischemic stroke who undergo endovascular intervention with dual antiplatelet therapy. The risk of ICH in patients with ≥ 5 CMBs, however, remains unclear. Further studies with a larger sample size of patients with multiple CMBs are needed.

A case of cerebral amyloid angiopathy with reversible white matter lesions and multiple cerebral microbleeds

A 59-year-old woman presented with a 7-year history of headache. She showed no neurological abnormality. T(2) weighted magnetic resonance (MR) images showed a hyperintense signal in the white matter in the bilateral parieto-occipital lobe without abnormal enhancement. A small amount of prednisolone was administered for rheumatoid arthritis. After prednisolone was discontinued, the T(2) weighted images showed an expansion of the hyperintense signal lesions seen in the white matter, and T(2) weighted image showed multiple foci of petechial bleeding in the cortex and subcortex of the bilateral occipital lobe. A brain biopsy specimen from the right occipital lobe revealed deposition of amyloid in the subarachnoidal and cortical vessel walls and transmural infiltration of a few lymphocytes, eosinophils, and giant histiocytes. Subsequently the patient was diagnosed with central nervous system vasculitis associated with cerebral amyloid angiopathy (CAA). After 5 months, the T(2) weighted images showed a remarkable regression of the hyperintense signal lesions in the white matter of the bilateral parieto-occipital lobe without the administration of any maintenance immunosuppressive agents. However, T(2) weighted image showed an increase of multiple cortico-subcortical foci of petechial bleeding. Her headache did not improve during the illness. Thus, we should consider the diagnosis of CAA when patients present with reversible white matter lesions and multiple cerebral microbleeds simultaneously.

Cerebral microbleeds, retinopathy, and dementia

To determine whether microvascular damage, indicated by cerebral microbleeds (CMBs) and retinal microvascular signs, is associated with cognitive function and dementia in older persons. This is a cross-sectional study of 3,906 participants (mean age 76 years; 58% women) in the AGES-Reykjavik Study (2002-2006). We assessed CMBs on MRI and retinal microvascular signs on digital retinal images. Composite Z scores of memory, processing speed, and executive function were derived from a battery of neurocognitive tests. Dementia and subtypes were diagnosed following international criteria. Regression models were used to relate cognitive Z scores and dementia to CMBs and retinal microvascular signs, adjusting for demographics, cardiovascular factors, and brain ischemic lesions. People with multiple (≥ 2) CMBs had lower Z scores on tests of processing speed (β-coefficient -0.16; 95% confidence interval -0.26 to -0.05) and executive function (-0.14; -0.24 to -0.04); results were strongest for having multiple CMBs located in the deep hemispheric or infratentorial areas. The odds ratio of vascular dementia was 2.32 (95% confidence interval 1.02 to 5.25) for multiple CMBs and 1.95 (1.04 to 3.62) for retinopathy. Having both CMBs and retinopathy, compared to having neither, was significantly associated with markedly slower processing speed (-0.25; -0.37 to -0.12), poorer executive function (-0.19; -0.31 to -0.07), and an increased odds ratio of vascular dementia (3.10; 1.11 to 8.62). Having multiple CMBs or concomitant CMBs and retinopathy is associated with a profile of vascular cognitive impairment. These findings suggest that microvascular damage, as indicated by CMBs and retinopathy lesions, has functional consequences in older men and women living in the community.

Steroid-responsive edema in CAA-related inflammation

JO N 3136 An 80-year old woman was admitted with sudden right-sided hemiparesis, dysphasia and altered mental status. There was no preceding infection or vaccination. She had an epileptic seizure after which we started phenytoin. Vital signs were BP 130/70, pulse 87, temperature 37.1 °C. MRI revealed white matter abnormalities, exerting a slight mass effect (Fig. 1 A). No gadolinium enhancement was observed. Serum and cerebrospinal fluid studies were within normal limits. After exclusion of infection we started dexamethasone 4 mg/ day and observed a clear recovery. The initial follow-up MRI was comparable with the previous MRI. Diffusion weighted images suggested that the white matter abnormalities represented vasogenic edema (Fig. 1 D). A T2*-weighted gradient echo sequence revealed multiple petechial hemorrhages or cerebral microbleeds (CMB, Fig. 1 B). In the absence of the classical vascular risk factors, we diagnosed CAA and continued dexamethasone in a gradually tapering scheme. The patient recovered, but relapsed after two months. She responded well to a temporary increase of dexamethasone. Four months later we could stop the dexamethasone. She had a mild residual dysphasia with a full recovery of cognition. Repeated MRI showed a clear reduction in brain edema (Fig. 1 C). Following the Boston criteria [3], we classified our patient as ‘probable CAA’. Post-mortem neuropathological examination is still considered the most reliable tool for diagnosing CAA. CAA can be identified in vivo by histological analyses upon evacuating a hematoma or by cortical biopsy. Because our patient responded well to steroid treatment, we did not perform a brain biopsy. The need for biopsy in the diagnosis of CAA is likely to decrease in the future, since KnudRichard Daniels Jeroen J. G. Geurts Joost C. Bot Wouter J. Schonewille Bob W. van Oosten

Retinal and Cerebral Microvascular Signs and Diabetes

Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes. The analysis included 4,218 participants of the Icelandic population-based Age, Gene/Environment Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing, arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated from magnetic resonance images. Data were analyzed with logistic and multinomial logistic regression models controlling for demographics, major cardiovascular risk factors, cerebral infarcts, and white matter lesions. Evidence of brain microbleeds was found in 485 (11.5%) people, including 192 with multiple (>or=2) microbleeds. Subjects with signs of retinal microvascular lesions were at a significantly increased likelihood for having multiple CMBs. People with diabetes in combination with the presence of either retinal AV nicking (odds ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28 [1.24-4.18]) were significantly more likely to have multiple CMBs. Retinal microvascular abnormalities and brain microbleeds may occur together in older adults. People with both diabetes and signs of retinal microvascular lesions (AV nicking and microaneurysms/hemorrhages) are more likely to have multiple microbleeds in the brain. Microvascular disease in diabetes extends to the brain.

B leeding R isk A nalysis in S troke I maging Before Thrombo L ysis (BRASIL)

There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients. We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by >or=4 points, temporally related to a parenchymal hematoma on follow-up-imaging. A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with >or=5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fisher's exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, -2.0 to 8.3). The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

Images in Neurology: Cerebral Microbleeds Due To Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) refers to the deposition of beta amyloid in the small and medium sized arteries of the brain and predisposes the individual to primary intracranial hemorrhage (PICH), dementia and transient neurological events. A-75-year-old non-diabetic, normotensive male presented to us with history of sudden onset of abnormal behavior characterized by irrelevant talking and straying on the road for about 20 minutes followed by spontaneous recovery. At the time of presentation to the emergency room his neurological examination was non-focal with no deficits. Gradient echo brain magnetic resonance imaging (MRI) as a part of stroke work up revealed multiple small chronic hemorrhagic lesions (microbleeds) suggestive of CAA (Fig 1 and 2). CAA is an important cause of PICH in the elderly accounting for up to 10% of all PICH in this age group. Patients with CAA may remain asymptomatic or may present with transient ischemic attacks or a devastating PICH. A definitive diagnosis of CAA rests on pathological examination of the affected blood vessel however gradient echo magnetic resonance imaging is a sensitive and noninvasive technique and the presence, number and distribution of microbleeds has a strong correlation with future PICH and cognitive decline 1. It is important to request gradient echo sequences if a diagnosis of CAA is been considered as convention MRI sequences like diffusion weighted imaging may miss these microbleeds. Currently there is no effective treatment for CAA though research continues to find an effective anti-amyloid therapy. There are no clear guidelines regarding anti-thrombotic therapy in patients with CAA. It makes sense to treat cardiovascular risk factors like hypertensive, dyslipidemia and diabetes aggressively in these patients. The decision regarding anti-platelet therapy needs to be individualized taking into consideration the patient's cardiovascular profile. Our patient currently remains asymptomatic on daily aspirin therapy. Figure 1 Figure 1&2: Gradient echo magnetic resonance imaging showing multiple cerebral microbleeds suggestive of chronic hemorrhagic lesions.

Cerebral microbleeds and intravenous thrombolysis: case report

Intravenous thrombolysis is an important procedure that has significant impact on ischemic stroke prognosis. However, intracranial hemorrhage (ICH) is a feared complication of this procedure. It has been suggested that cerebral microbleeds (CMBs) may increase the risk of ICH after thrombolysis. We report on a 69 years-old woman with multiple CMBs submitted to intravenous thrombolysis without complications.

O3-04-07: Prevalence and risk factors of cerebral microbleeds in the Rotterdam scan study

Cerebral microbleeds (CMB) reflect small vessel disease and can be visualized with T2*–GRE magnetic resonance imaging (MRI). Their location may be related to different causative factors, since symptomatic deep grey matter hemorrhages are related to hypertension and lobar hemorrhages to cerebral amyloid angiopathy (CAA). Anticoagulants may be associated with CAA–related hemorrhages. Little is known on the occurrence of CMBs in the general population. We conducted an MRI study in healthy elderly persons to assess the prevalence and distribution of and the risk factors for CMBs. The study is based on 491 randomly selected participants (mean age 67.1; range 60.7–91.7) from the Rotterdam Study, a population–based cohort study among participants aged 55 years and older. We performed a custom–designed T2*–GRE susceptibility–weighted MR–sequence, with higher T2* weighting and smaller voxel size than commonly used T2*–GRE sequences, to increase the conspicuity of CMBs. Two raters scored the presence, location and number of CMBs. Intra–rater and inter–rater reliabilities were good to excellent. Cardiovascular risk factors were assessed by interview and physical examination, 5 years prior to and at the time of MRI. Associations between risk factors and CMBs were assessed by logistic regression and adjusted for age, sex, and relevant confounders. One or more CMBs were seen in 84 (17.1%) participants, with multiple microbleeds in 37, of whom 20 had five or more CMBs. Of participants with microbleeds, 80% had CMBs located in cortical grey and subcortical white matter, 24% in deep grey and white matter, and 27% had CMBs infratentorial. The prevalence of CMBs significantly increased with age (OR per year 1.05; 95%CI 1.01; 1.09). This association was particularly strong for multiple CMBs (OR per year 1.11; 95%CI 1.04; 1.17). Prior high systolic blood pressure was significantly related to CMBs in deep grey matter, but not to CMBs elsewhere, whereas use of antithrombotics showed a significant association with cortico–subcortical CMBs. Compared to previous studies, we found a two– to threefold higher prevalence of CMBs in a healthy elderly population. The prevalence of CMBs increased with age. Our initial analyses suggest an etiologic difference in CMBs in different locations.

Multiple Cerebral Microbleeds in Hyperacute Ischemic Stroke: Impact on Prevalence and Severity of Early Hemorrhagic Transformation After Thrombolytic Treatment

The purpose of our study was to assess whether cerebral microbleeds are related to early hemorrhagic transformation after thrombolytic therapy for hyperacute ischemic stroke. The cases of 279 patients with suspected ischemic stroke who underwent MRI including T2*-weighted images were retrospectively evaluated. The inclusion criteria were as follows: imaging performed within 6 hr after symptom onset, presence of territorial infarct of anterior circulation, no history of intracerebral hemorrhage, thrombolytic treatment, and available follow-up MR images. Microbleeds were classified according to number as follows: absent (grade 1, 0 bleeds), mild (grade 2, 1-2 bleeds), moderate (grade 3, 3-10 bleeds), and severe (grade 4, > 10 bleeds). The prevalence and severity of early hemorrhagic transformation after thrombolysis were assessed on follow-up images. Among 279 patients, 65 patients (37 men, 28 women; mean age, 67 years) met the inclusion criteria. Microbleeds were found in 25 patients. Early hemorrhagic transformation occurred in nine of 40 patients without microbleeds (grade 1) and in eight of 25 patients with microbleeds: two of 12 patients with grade 2, three of eight patients with grade 3, and three of five patients with grade 4 microbleeds. The presence of symptomatic hemorrhage did not correlate with the number of microbleeds. Results of multivariate logistic regression analysis showed that the presence of microbleeds was not associated with hemorrhagic transformation after thrombolytic treatment. Small and large numbers of microbleeds are not independent risk factors for early hemorrhagic transformation and symptomatic hemorrhage after thrombolytic therapy for hyperacute ischemic stroke. Additional studies with large groups of subjects are needed to confirm our conclusion.

Primary Medullary Hemorrhage Associated with Hypertension

Spontaneous primary medullary hemorrhage is a rare event. A 64-year-old man was admitted for sudden-onset vertigo and vomiting. His clinical features were similar to those of lateral medullary syndrome. The patient had no anticoagulant therapy, vascular malformation, or a caudal extension of a pontine hemorrhage. The patient had multiple hypertensive changes, including retinopathy, left ventricular hypertrophy on electrocardiography, multiple cerebral microbleeds, and small-vessel changes on MRI. T2*-weighted gradient echo MRI performed 3 months prior to admission and contrast-enhanced MRI showed no evidence of vascular malformation. We concluded that the patient had uncontrolled hypertension that may have lead to primary medullary hemorrhage.

Multiple Cerebral Microbleeds: Mri Marker of a Diffuse Hemorrhage–Prone State

ABSTRACT Background. Recent reports have indicated that cerebral microbleeds (CMBs) detected on gradient‐echo (GRE) magnetic resonance imaging may be a risk factor for therapy‐related intracranial hemorrhages (ICHs). Case Description. The authors describe 3 patients with multiple CMBs in whom ICHs occurred either after tissue plasminogen activator administration or after the initiation of antiplatelet therapy. Hemorrhages occurred in brain areas with normal appearances on GRE imaging and remote from the CMBs. Conclusion. Multiple CMBs may signal a diffuse hemorrhage–prone vasculopathy.

Multiple Cerebral Microbleeds: Mri Marker of a Diffuse Hemorrhage–Prone State

Recent reports have indicated that cerebral microbleeds (CMBs) detected on gradient-echo (GRF) magnetic resonance imaging may be a risk factor for therapy related intracranial hemorrhages (ICHs). The authors describe 3 patients with multiple CMBs in whom ICHs occurred either after tissue plasminogen activator administration or after the initiation of antiplatelet therapy. Hemorrhages occurred in brain areas with normal appearances on GRE imaging and remote from the CMBs. Multiple CMBs may signal a diffuse hemorrhage-prone vasculopathy.