Impact of albuminuria on early neurological deterioration and lesion volume expansion in lenticulostriate small infarcts.

BACKGROUND AND PURPOSE: Albuminuria, a marker of chronic kidney disease, is associated with an increased risk of incident stroke and unfavorable long-term outcomes. However, the association of albuminuria with short-term outcomes and change in infarct volume in patients with acute small subcortical infarction remains unknown. METHODS: We retrospectively reviewed 85 consecutive patients with acute small subcortical infarcts in the lenticulostriate artery territory who were admitted to our stroke center within 24 hours of symptom onset and underwent serial diffusion-weighted imaging (DWI). Albuminuria was determined based on the urinary albumin-to-creatinine ratio obtained from a first morning spot urine after admission. Infarct volume was measured on axial sections of the initial and follow-up DWI. Early neurological deterioration (END) was defined as an increase of ≥2 points in the National Institutes of Health Stroke Scale score during the first 5 days after admission. RESULTS: Albuminuria (UACR ≥30 mg/g creatinine) was observed in 14 of 18 patients with END (77.8%) and in 25 of 67 patients without END (37.3%), P=0.002. Multivariate logistic regression analysis revealed that albuminuria was associated with END after adjustment for age, low estimated glomerular filtration rate (<60 mL/min per 1.73 m2), and infarct volume on initial DWI (odds ratio, 6.64; 95% confidence interval, 1.62-27.21; P=0.009). In addition, albuminuria was an independent predictor of increase in infarct volume using multivariate linear regression analysis (ß coefficient=0.217; P=0.038). CONCLUSIONS: Our findings suggest that albuminuria is associated with END and infarct volume expansion in patients with small subcortical infarcts in the lenticulostriate artery territory.

Association of chronic kidney disease and cerebral small vessel disease with cognitive impairment in elderly patients with type 2 diabetes.

BACKGROUND/AIMS: In recent years, the relationship between chronic kidney disease (CKD) and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD) is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. METHODS: Seventy-nine type 2 diabetic patients (mean age, 76.0 years) were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m(2)). SVD was evaluated by the presence and severity of silent brain infarcts (SBIs) and white matter lesions (WMLs) on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. RESULTS: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (ß = 0.284, p = 0.017) and low eGFR was associated with reduced Digit Symbol Substitution scores (ß = -0.224, p = 0.026) after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. CONCLUSION: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

[Following sensory neuropathy, anti-Hu antibody-positive paraneoplastic neurological syndrome presenting with limbic encephalitis occurs after complete remission].

Paraneoplastic limbic encephalitis is a rare neurological disorder that frequently precedes the detection of malignancy. We report the case of a 68-year-old male with small-cell lung cancer who developed paraneoplastic limbic encephalitis associated with presence of the anti-Hu antibody, after achieving complete remission of the tumor by chemotherapy. The patient visited our hospital because of progressive sensory disturbance of the distal extremities at 65 years of age. Though paraneoplastic sensory neuropathy was suspected, we could not find any tumor and he did not improve with steroids or immunoglobulin therapy. Chest computed tomography (CT) revealed large mediastinal lymphadenopathy. He was subsequently diagnosed with small cell lung cancer at one year and three months after the neurological symptoms occurred. As his serum analysis was positive for the anti-Hu antibody, we diagnosed paraneoplastic sensory neuropathy. The lung cancer disappeared with chemotherapy, but he had developed short-term memory loss six months later. Brain fluid attenuated inversion recovery (FLAIR) imaging showed an abnormal high-intensity lesion in the left medial temporal lobe including the hippocampus. We therefore made the diagnosis of paraneoplastic limbic encephalitis following subacute sensory neuropathy associated with the anti-Hu antibody. To our knowledge, this is the first report of a patient presenting with paraneoplastic neurological syndrome in which limbic encephalitis developed after tumor disappearance. So we must recognize the possibility of neurological symptoms occurring during remission. As the mechanism of pathogenesis, delayed neuronal cell damage due to immune responses against the tumor is implicated.

Microalbuminuria is independently associated with deep or infratentorial brain microbleeds in hypertensive adults.

BACKGROUND: Brain microbleeds (BMBs) detected on gradient echo T2*-weighted magnetic resonance imaging (GE-MRI) may be pathophysiologically linked to ischemic cerebral small-vessel disease (SVD) and increased risk of future hemorrhagic stroke. Chronic kidney disease (CKD) has been associated with the presence of BMBs in stroke patients. However, the relationship between CKD markers and BMBs in stroke-free populations is unknown. METHODS: Two hundred and eighty-five hypertensive subjects (mean age 68.6 years) without neurological symptoms were enrolled from a hospital-based outpatient clinic and all participants underwent GE-MRI. We calculated urinary albumin/creatinine ratio (UACR) from morning spot urine and the estimated glomerular filtration rate (eGFR) in serum samples. Multivariate logistic regression analysis was used to evaluate the association between these kidney biomarkers and the presence and location of BMBs, controlling for age, sex, use of antihypertensive or antithrombotic drugs, and MRI findings. RESULTS: BMBs were observed in 48 (16.8%) patients. Median UACRs were significantly higher in patients with deep or infratentorial BMBs than in patients with pure lobar BMBs (54 vs. 17 mg/g creatinine, P = 0.04). No significant differences were found between eGFR levels and the location of BMBs. Microalbuminuria (UACR >30- ≤300 mg/g creatinine), but not low eGFR level was significantly associated with higher prevalence of deep or infratentorial BMBs (odds ratio (OR): 3.16, 95% confidence interval (CI): 1.34-7.44, P = 0.009) even after adjustment for potential confounding factors. CONCLUSIONS: Microalbuminuria is closely associated with the prevalence of deep or infratentorial BMBs in hypertensive patients. Our findings provide new insights into the association between risk factors and the distribution of BMBs.

Does cerebral small vessel disease predict future decline of cognitive function in elderly people with type 2 diabetes?

AIMS: We conducted a 3-year longitudinal study concerning an association between cognitive function and cerebral small vessel disease (SVD) seen on magnetic resonance imaging (MRI) in elderly type 2 diabetic patients. METHODS: Four cognitive function tests--MMSE, word recall, Digit Symbol Substitution (DSS), and Stroop Color Word (Stroop)--were performed in 67 diabetic patients twice in 2006 and 2009. SVD was diagnosed as silent brain infarct (SBI) and white matter lesions (WMLs) according to MRI. RESULTS: Number of SBI was significantly correlated with a decline in DSS and Stroop tests, while WMLs grade was only associated with it in DSS tests after adjustment for age, gender, education years, the presence of hypertension and dyslipidemia, and smoking. Severity of SVD at baseline was stronger associated with cognitive function after the 3-year follow-up than at baseline. WMLs progression was associated with more rapid decline of DSS tests compared to a group without progression. CONCLUSIONS: SVD seen on MRI is a good marker for predicting future cognitive decline, and monitoring of treatment through the use of such markers is expected to maintain a good quality of life for elderly diabetic patients.

Association of soluble adhesion molecule and C-reactive protein levels with silent brain infarction in patients with and without type 2 diabetes.

Silent brain infarction (SBI) is often detected on MR imaging, however the pathogenesis is still unclear. We aimed to investigate and compare the association of soluble adhesion molecules and C-reactive protein levels with the prevalence of SBI in patients with and without diabetes mellitus. We recruited 130 patients (mean age 59.6 +/- 7.6 yrs) with type 2 diabetes and 130 age- and sex-matched non-diabetic subjects. All subjects underwent head MRI to determine SBI. We measured levels of soluble intercellular adhesion molecule 1(sICAM-1), vascular cell adhesion molecule 1(sVCAM-1), and high sensitivity C-reactive protein (hs-CRP) and evaluated intima-media complex thickness (IMT) in common carotid arteries by ultrasound B-mode imaging. SBI was present in 36 (27.7%) of the diabetic patients and 31 ( 23.8%) of the non-diabetic subjects. Levels of sICAM-1, sVCAM-1 and IMT were all significantly higher in diabetic patients than in non-diabetic subjects, and were significantly increased in both subjects with SBI. IMT was only positively correlated with sVCAM-1 levels in diabetic and non-diabetic subjects. On the other hand, hs-CRP levels were not significantly different in both subjects with and without SBI. In addition, sICAM-1 levels were associated with a significantly higher relative risk for the prevalence of SBI in diabetic patients after multivariate adjustment. Our study suggests that the associations between endothelial dysfunction and presence of SBI may be stronger in diabetic patients than in nondiabetic subjects. In particular, sICAM-1 may play an important role for the pathogenesis of SBI in patients with diabetes mellitus.