Cerebral Microbleeds: Their Associated Factors, Radiologic Findings, and Clinical Implications / 대한뇌졸중학회지

Cerebral microbleeds (CMBs) are tiny, round dark-signal lesions that are most often detected on gradient-echo MR images. CMBs consist of extravasations of blood components through fragile microvascular walls characterized by lipohyalinosis and surrounding macrophages. The prevalence of CMBs in elderly subjects with no history of cerebrovascular disease is around 5%, but is much higher in patients with ischemic or hemorrhagic stroke. Development of CMBs is closely related to various vascular risk factors; in particular, lobar CMBs are thought to be associated with cerebral amyloid angiopathy. The presence of CMBs has been hypothesized to reflect cerebral-hemorrhage-prone status in patients with hypertension or amyloid microangiopathy. Stroke survivors with CMBs have been consistently found to have an elevated risk of subsequent hemorrhagic stroke or an antithrombotic-related hemorrhagic complication, although studies have failed to establish a link between CMBs and hemorrhagic transformation after thrombolytic treatment. A large prospective study is required to clarify the clinical significance of CMBs and their utility in a decision-making index.

The Relationship of Matrix Metalloproteinase-9 and Microbleeds on T2*-Weighted Gradient-Echo MRI in Acute Lacunar Infarction

BACKGROUND: Hypointense cerebral lesions on T2*-weighted gradient-echo MRI (GRE) have been known to be related with microbleeds or advanced microangiopathy with potential for further bleeding. It has also been suggested that matrix metalloproteinases (MMPs) may play a role in blood brain barrier disruption, edema formation and hemorrhagic transformation. In this study, we investigated the relationship between microbleeds detected by GRE, MMPs and neurological worsening in acute lacunar infarctions. METHODS: Eighty-eight patients with acute lacunar infarctions, defined by TOAST classification, were included. GRE (1.5T, TR 500 ms TE 15 ms) was performed within 48 hours after stroke symptom onset. MMPs were measured by standard quantitative sandwich enzyme-linked immunosorbent assays (ELISA). Clinical characteristics, neurologic scale and MMP-9 levels were compared between groups with or without hypointense lesions in GRE (microbleeds). Neurological worsening was defined as deterioration from baseline in the score on the NIHSS by one or more points 14 days after the onset of a lacunar infarction. RESULTS: Eleven of 88 patients (12.5%) undergoing GRE demonstrated evidence of microbleeds in the ischemic region. In the groups with microbleeds, the ESR level (p=0.048) and MMP-9 activity (p=0.001) were significantly increased, and neurological worsening was more prominent (p=0.018). CONCLUSIONS: This study suggests that microbleeds detected by GRE are related with elevated MMP-9 and neurological worsening. Therefore, the finding of microbleeds in GRE, increased MMP-9 activity and elevated ESR level might be useful factors for predicting the progression of acute lacunar infarctions.

Correlation between Multifocal Hypointense Cerebral Lesions on Gradient-echo MRI and White Matter Changes in Patients with Stroke

BACKGROUND: The multifocal hypointense cerebral lesions (MHCLs) on gradient echo (GE)-MRI and white matter changes on T2WI have been thought to be indicative of microangiopathy. The purpose of this study is to elucidate the relationship between MHCLs and white matter (WM) changes and the clinical significance of WM changes in stroke patients. METHODS: We retrospectively reviewed MRI and clinical data of 115 patients with stroke (56 female and 59 male). Periventricular and deep white matter hyperintensity (PVHI and DWMHI) were measured by semiquantative rating scale proposed by Mantyla. The round, hypointense signal, less than 7 mm in diameter on GE-MRI were counted as MHCLs. The association between risk factors of stroke and MHCLs on GE-MRI and sum of the white matter change scores and total number of MHCLs were analyzed, respectively. RESULTS: MHCLs on GE-MRI were significantly associated with old age (p<0.05) and hypertension (p<0.001) among risk factors of stroke. The distribution of MHCLs in subcortical area is associated with hypertension (p<0.05) and total number of MHCLs was significantly associated with sum of the white matter change scores (p<0.05). CONCLUSIONS: MHCLs on GE-MRI were significantly associated with severity of WM changes. Severe WM change may be an indicator of advanced small artery disease of the brain with an increased risk factor for bleeding. This should be taken into consideration when treating patients with stroke.

Usefulness of Apolipoprotein E4 and Distribution of Petechial Hemorrhages in Differentiating between Cerebral Amyloid Angiopathy and Hypertensive Intracerebral Hemorrhage

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy (CAA) accounts for a significant proportion of spontaneous lobar hemorrhages in the elderly population but hypertension is responsible for most cases of deep-seated hemorrhage. Reportedly petechial hemorrhages (PHs) can be associated with CAA or chronic hypertension. We determined the location of PHs and apolipoprotein E (APOE) genotype in intracerebral hemorrhage (ICH) patients and tried to correlate them with CAA associated or hypertensive ICH. METHODS: One hundred and sixty-two consecutive patients with primary ICH were evaluated clinically and by MRI. PHs were defined as small low-signal lesions (less than 1 cm) seen on T2-weighted or gradient-echo MR images. ICH and PHs were divided into lobar (cortical-corticosubcortical), deep (basal ganglia, thalamus, pons, or cerebellum), or mixed. APOE genotype was determined by polymerase chain reaction. All 162 patients were classified into 4 groups: 1) probable CAA (multiple lobar bleeds without other cause), 2) possible CAA (single lobar bleed), 3) probable hypertensive ICH (deep bleed), and 4) mixed lobar and deep hemorrhages. RESULTS: Among 162 patients, 31 belonged to the probable and possible CAA groups and 17 of them showed PHs (7 lobar, 4 deep, 6 mixed). One hundred and twenty-two patients were the hypertensive ICH group and 63 of them had PHs (2 lobar, 10 mixed, 51 deep). Lobar PHs were more frequently observed in the probable and possible CAA group than the hypertensive ICH group (22.6%: 1.6%, p < 0.01) while deep PHs were seen mainly in the hypertensive ICH group (41.8%: 12.9%, p < 0.01) and these tendencies are also observed in the group who had taken both T2-weighted and gradient-echo MR images (64 patients). The frequency of hypertension was significantly lower in the probable and possible CAA groups with lobar PHs than in the hypertensive ICH group with deep PHs (57.1%: 98 %, n = 7 & 51 respectively, p < 0.01). APOE ?4 frequency was: probable (freq. 0.25, n = 2), possible CAA (freq. 0.21, n = 7), hypertensive (freq. 0.056, n = 9), and mixed hemorrhages (freq. 0.071, n = 7). The frequency of APOE ?4 of probable and possible CAA group seems to be higher than that of normal control (freq. 0.19, n = 146). CONCLUSION: APOE ?4 and PHs in lobar areas may be associated with hemorrhages restricted to lobar regions while hypertension and PHs in deep areas, with hemorrhages restricted to deep regions.