Association of mild kidney dysfunction with silent brain lesions in neurologically normal subjects.

BACKGROUND: Chronic kidney disease (CKD) has been closely associated with stroke. Although a large number of studies reported the relationship between CKD and different types of asymptomatic brain lesions, few comprehensive analyses have been performed for all types of silent brain lesions. METHODS: We performed a cross-sectional study involving 1,937 neurologically normal subjects (mean age 59.4 years). Mild CKD was defined as an estimated glomerular filtration rate between 30 and 60 ml/min/1.73 m(2) or positive proteinuria. RESULTS: The prevalence of mild CKD was 8.7%. Univariate analysis revealed an association between CKD and all silent brain lesions, including silent brain infarction, periventricular hyperintensity, subcortical white matter lesion, and microbleeds, in addition to hypertension and diabetes mellitus after adjusting for age and sex. In binary logistic regression analysis, the presence of CKD was a significant risk factor for all types of silent brain lesions, independent of other risk factors. CONCLUSIONS: These results suggest that mild CKD is independently associated with all types of silent brain lesions, even in neurologically normal subjects.

[Diagnosis and treatment of brain microbleeds].

Brain microbleeds (MBs) are represented as low-intensity spotty lesions on T2 *-weighted MR images and are frequently detected in healthy people and not only stroke patients. A recent meta-analysis revealed that MBs were present in 34% of patients with ischemic stroke and 60% with intracerebral hemorrhage, respectively. On the other hand, MBs only occur in approximately 4-6% of subjects without cerebrovascular disease and neurological symptoms. The occurrence of MBs in healthy elderly subjects is associated with advanced age or chronic hypertension. The pathological findings of MBs depend on the region of the brain, in which lobar and deep brain MBs are associated with cerebral amyloid angiopathy and hypertensive vasculopathy, respectively. To prevent stroke, risk factors should be carefully managed in subjects with MBs factors. Since hypertension was also found in all subjects who experienced stroke after presenting with MBs, such patients should be treated with intensive anti-hypertensive medication to prevent subsequent ischemic or hemorrhagic stroke. Additionally, antithrombotic drugs should be carefully used in patients with MBs.

A discrepancy between clinical course and magnetic resonance imaging in a case of non-herpetic acute limbic encephalitis.

We report the case of a 64-year old man who presented memory disturbance, low-grade fever, weight loss, and bilateral hand tremors for three months. He was diagnosed with non-herpetic acute limbic encephalitis (NHALE). Follow-up magnetic resonance imaging (MRI) revealed new lesions after symptomatic improvement following steroid pulse therapy. This may indicate that there is a time lag between the disturbance or recovery of neurons and astrocytes. Thus, other lesions might occasionally appear during convalescence in patients with NHALE, even if only minimal lesions were found on the initial MRI.

The effect of ropinirole on apathy and depression after herpes encephalitis.

We describe a 76-year-old man with herpes encephalitis whose symptom of severe apathy was improved by the dopamine D2/D3 receptor agonist ropinirole. Brain magnetic resonance imaging had shown lesions in the patient's right mesial temporal cortex, right insula, and bilateral medial frontal regions. During treatment with acyclovir, he had developed severe apathy and depression. On neuropsychological assessment, he scored 21/30 points on the Mini-Mental State Examination, 30/42 on the Starkstein Apathy Scale (cutoff score =16), and 59/80 on the Zung Self-Rating Depression Scale (cutoff score=40). We then started him on ropinirole 0.25 mg/day. Over the next 10 days, his apathy and depression gradually improved. On day 10 of treatment, follow-up testing showed that his Apathy Scale score had improved to 25 points. This case suggests that a low dose of a dopamine receptor agonist may be an effective treatment for patients who develop apathy and depression after encephalitis.

Cerebral embolism associated with left atrial myxoma that was treated with thrombolytic therapy.

We present a case of cerebral embolism associated with a left atrial myxoma that was treated with intravenous thrombolytic therapy. A 79-year-old right-handed man with no history of neurological or psychiatric illnesses was referred to our hospital because of confusion. He had been self-supported in the activity of daily living and could enjoy gardening until just before his admission. He had aphasia, left conjugate deviation, right hemiparesis, and right pathological reflexes. His NIHSS score was 24. Cranial DWI showed hyperintense lesions in the left middle cerebral artery territory, and MRA revealed left middle cerebral artery occlusion. We started treatment with the recombinant tissue plasminogen activator alteplase intravenously 3 h after the onset. However, the therapy was ineffective, and the NIHSS score was 25 on the second day. A transthoracic echocardiogram and heart MRI showed a left atrial myxoma. However, surgery was contraindicated because of the patient's poor general condition. Although intravenous recombinant tissue plasminogen activator is a reasonable treatment for stroke patients, even with a cardiac myxoma, we cannot always expect good effects, especially if the emboli are parts of the tumor itself. In this case, we could not perform an endovascular mechanical embolectomy; however, we speculate that mechanical embolus retrieval in cerebral ischemia might be effective in such cases.

Association of cognitive dysfunction with hippocampal atrophy in elderly Japanese people with type 2 diabetes.

This study aimed to examine the associations of cognitive function with hippocampal and whole brain atrophies, age, education, and diabetes-related parameters in patients with type 2 diabetes. Sixty-one patients over 65 years of age with type 2 diabetes and 53 age- and sex-matched non-diabetic controls were enrolled. Hippocampal and whole brain atrophies were assessed by quantifying hippocampal and brain volumes by brain magnetic resonance imaging. Cognitive function was evaluated by Mini-Mental State Examination (MMSE) and the Revised Hasegawa Dementia Scale (HDS-R). Compared with the non-diabetic group, patients with type 2 diabetes showed significant increases in hippocampal and whole brain atrophies. The MMSE and HDS-R scores in type 2 diabetic patients showed significant negative correlations with age and significant positive correlations with years of education. These scores were also significantly negatively correlated with hippocampal atrophy, but not whole brain atrophy. Hippocampal atrophy in diabetic patients did not, however, correlate with age, years of education, or diabetes-related parameters. We showed hippocampal and whole brain atrophies to be more frequent in elderly patients with type 2 diabetes than in non-diabetic controls. Their cognitive functions were significantly and negatively associated with hippocampal atrophy.

Microbleeds are associated with subsequent hemorrhagic and ischemic stroke in healthy elderly individuals.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals. METHODS: We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject. RESULTS: MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region. CONCLUSIONS: This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.

Post-stroke apathy and hypoperfusion in basal ganglia: SPECT study.

BACKGROUND: Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there are few studies on regional cerebral blood flow (rCBF) in stroke patients with apathy. The present study compared rCBF between apathetic and non-apathetic patients after stroke. METHODS: We recruited 102 patients with cerebral infarction within 1 month after stroke and performed neuropsychiatric assessments that included the apathy scale. rCBF was quantitatively measured using N-isopropyl-p-(123)I-iodoamphetamine single-photon emission computed tomography. RESULTS: Thirty-seven patients (36%) had apathy. The apathetic group showed lower cognitive function and a higher depressive state than the non-apathetic group. rCBF in the basal ganglia was reduced for the apathetic group compared with the non-apathetic group. Furthermore, lesions in the left basal ganglia were associated with hypoperfusion in bilateral basal ganglia and the presence of apathy. CONCLUSION: These findings demonstrate that apathy is a frequent symptom among stroke patients and that hypoperfusion caused by basal ganglia lesions may contribute to post-stroke apathy.

Age-related changes in white matter lesions, hippocampal atrophy, and cerebral microbleeds in healthy subjects without major cerebrovascular risk factors.

Although cumulative evidence indicates that risk factors for arteriosclerosis have an impact on age-related changes in brain pathology, the influence of aging without major risk factors on changes in brain structures has not yet been fully elucidated. We used magnetic resonance imaging (MRI) to study how aging affects structural changes in the brain (eg, white matter lesions, hippocampal atrophy [HA], microbleeds) in normal subjects without major risk factors for cerebrovascular diseases. We studied 1108 subjects who underwent voluntary brain screening and had no cerebrovascular risk factors, such as hypertension, diabetes mellitus, or hyperlipidemia. We examined the conventional and T2-weighted MRI to define white matter hyperintensities, HA, and cerebral microbleeds in addition to all physical parameters, blood biochemical data, and neuropsychiatric symptoms. We found that the prevalence of white matter lesions and HA increased significantly with age (P < .001). Logistic analysis showed that periventricular hyperintensity was significantly related to age (P < .0001) and depressive state (P < .01). A linear relation was found between white matter lesions and HA (P < .05). Cerebral microbleeds also increased with age, and their presence was associated with HA (P < .001). White matter lesions, HA, and cortical microbleeds were associated with one another in healthy elderly subjects, and these changes were affected by the aging process independent of any cerebrovascular risk factors. Cerebral amyloid angiopathy may underlie these age-related brain changes.

Successful treatment of post-stroke apathy by the dopamine receptor agonist ropinirole.

Dopamine D2/3 receptor agonists have been widely used to treat motor symptoms in Parkinson's disease and are also reported to improve cognitive and emotional disturbances. Here we describe a patient who developed severe apathy after cerebral infarction in the prefrontal cortex. After administration of ropinirole, his verbal output and spontaneity in daily life was improved remarkably. This improvement was associated with increased blood flow in the prefrontal cortex and basal ganglia. We suggest that ropinirole may be a treatment option for deficits in motivated behavior after prefrontal damage.

[Efficacy of tissue plasminogen activator in older patients].

AIM: To evaluate the efficacy, outcome, and side effects of tissue plasminogen activator for cerebral infarction in patients aged 75 years or older. METHODS: Subjects consisted of 30 patients who had been treated with tissue plasminogen activator between October, 2005 and March 2009, in Shimane University Hospital. We divided the patients into two groups: those less than 75 years old and those 75 years old and older, and evaluated the pattern of disease, therapeutic efficacy, side effects of bleeding, and factors affecting the modified Rankin Scale on discharge. RESULTS: There was no significant difference between groups in the improvement level of NIH Stroke Scale (p=0.66), but modified Rankin Scale 2 or lower patients on discharge were significantly fewer (p=0.02). Multivariate analysis found that age was a factor in significant outcome deterioration (p=0.04, OR1.2). In the older patient group, there were significantly more unfavorable outcomes with anterior infarction. However, there was no significant difference between groups in outcome in patients with ASPECTS-DWI (Alberta Stroke Programme Early CT Score-Diffusion Weight Imaging) > or =8. There was no difference in the rate of hemorrhagic side effect between the two groups. CONCLUSION: We can expect effects similar to those in patients younger than 75 years if the ischemic lesions of older patients are narrow when coming to the hospital.

The association of metabolic syndrome with executive dysfunction independent of subclinical ischemic brain lesions in Japanese adults.

BACKGROUND/AIMS: The aim of this study is to examine whether metabolic syndrome is directly associated with cognitive impairment independent of subclinical ischemic brain lesions. METHODS: We examined 1,543 neurologically normal subjects (44-86 years of age). Metabolic syndrome, brain MRI, and cognitive functions including general cognition and executive function were assessed. RESULTS: After adjusting for silent brain lesions and demographic risk factors, metabolic syndrome was an independent risk factor for impairment of executive function (OR = 1.41, 95% CI = 1.17-1.25 for Kohs' Test; OR = 2.25, 95% CI = 1.64-3.07 for Frontal Assessment Battery). Among the components of metabolic syndrome, elevated fasting glucose was the only independent risk factor for impairment of executive function. CONCLUSION: Metabolic syndrome is associated with impairment of executive function independent of silent brain lesions in the Japanese population.

Evaluation of asymmetric dimethylarginine and homocysteine in microangiopathy-related cerebral damage.

BACKGROUND: Microangiopathy-related cerebral damage (MARCD) is an entity of cerebrovascular disease based on arteriosclerosis in deep white matter, which includes lacunar infarction and white matter hyperintensity (WMH). As asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide (NO) synthases, and homocysteine are both potential risk factors for arteriosclerosis, the plasma levels of these two substances were evaluated in individuals with MARCD. METHODS: Consecutive participants of a health examination (401 males and 311 females) were recruited for this cross-sectional study. All participants received an magnetic resonance imaging examination, and those with either lacunar infarction or WMH (grade > or =2) were classified into MARCD (+) (N = 146). The plasma ADMA concentration was measured with high performance liquid chromatography. The total homocysteine (tHcy) concentration was measured using a commercial kit. RESULTS: The ADMA level (P < 0.001), symmetric dimethylarginine (SDMA) level (P < 0.05) and L-arginine (Arg)/ADMA ratio (P < 0.01) differed significantly between MARCD (+) and (-) according to nonparametric Wilcoxon test, while the tHcy level did not (P = 0.37). Classic risk factors such as age, blood pressure, and the presence of hypertension differed significantly between the two groups as well. In the logistic analysis, the association of Arg/ADMA with MARCD remained significant (odds ratio and 95% confidence interval, 0.19 (0.05, 0.73), P < 0.05) even after adjusting for the effects of age and hypertension. CONCLUSIONS: ADMA and tHcy levels were studied in 712 subjects with or without MARCD. The Arg/ADMA ratio was suggested to be an independent risk factor for MARCD. A large-scale prospective study is warranted to confirm the causal relationship between Arg/ADMA and MARCD.

[A case of probable cytomegalovirus encephalitis who restored from persistant disturbance of consciousness].

A 50-year-old woman presented with confusion, fever and drowsiness following an episode of headache and dizziness. On admission, neurological examination found positive pyramidal tract signs, meningeal irritation, and bilateral myoclonus in her arms. Laboratory tests revealed liver dysfunction, positive inflammatory reaction, elevated serum IgM antibody against cytomegalovirus, and increased cerebrospinal fluid protein of 67 mg/dl. MRI of brain by diffusion weighted imaging showed a wide spread hyperintense lesion in white matter and limbic areas. We administered aciclovir, ganciclovir and steroid pulse therapy that showed a limited effect in the initial stage. In spite of all these therapies, she suffered from status epilepticus, followed by persistent disturbance of consciousness for about 2 months. However, her level of consciousness and motor deficit were gradually improved by continuous administration of ganciclovir. The present case indicates that prolonged disturbance of consciousness due to cytomegalovirus encephalitis could be restored with continuous ganciclovir administration.

[The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults].

AIM: We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. METHODS: MRI scans were performed on 109 neurologically normal adults (mean age, 58.6+/-5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. RESULTS: There were no differences in age, sex, dyslipidemia, BMI, smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. CONCLUSION: The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation.

Metabolic syndrome is associated with silent ischemic brain lesions.

BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is a recognized risk factor for stroke, but it is unclear whether MetS is also related to subclinical ischemic lesions. We examined the association of MetS with the prevalence of silent brain infarction, periventricular hyperintensity, and subcortical white matter lesions in healthy adults. METHODS: We conducted a cross-sectional study in 1151 Japanese healthy subjects. Three types of silent lesions were assessed by MRI scans. MetS was diagnosed using the criteria by the National Cholesterol Education Adult Treatment Panel III. RESULTS: After adjusting for age and other factors, MetS was significantly associated with silent brain infarction, periventricular hyperintensity and subcortical white matter lesions. Among the MetS components, elevated blood pressure was commonly associated with all types of lesions. Dyslipidemia and elevated fasting glucose levels were associated with subcortical white matter lesions and periventricular hyperintensities, respectively. Positive trends were observed between the number of MetS components and prevalence of silent lesions. CONCLUSIONS: MetS is associated with the prevalence of silent lesions independent of other risk factors. The clustering of MetS components tends to increase the prevalence of silent lesions.

The key locus of common response inhibition network for no-go and stop signals.

Response inhibition is one of the highest evolved executive functions of human beings. Previous studies revealed a wide variety of brain regions related to response inhibition, although some of them may not be directly related to inhibition but to task-specific effects or noninhibitory cognitive functions such as attention, response competition, or error detection. Here, we conducted event-related functional magnetic resonance imaging studies in which all subjects performed both stop-signal and go/no-go tasks in order to explore key neural correlates within the response inhibition network irrelevant to task designs and other cognitive processes. The successful inhibition in the stop-signal and go/no-go tasks, respectively, activated a set of predominantly right-lateralized hemispheric cortices. The common inhibitory regions across the two tasks included the right middle prefrontal cortex in addition to the right middle occipital cortex. Correlation analysis was carried out within these areas between intensity of activation and behavioral performance in the two tasks. Only the region located in the middle prefrontal cortex showed significant correlations in both tasks. We believe this region is the key locus for execution of response inhibition in the distributed inhibitory neural network.

Metabolic syndrome increases the risk of ischemic stroke in women.

BACKGROUND: Metabolic syndrome is a characterized by a cluster of cardiovascular risk factors, including visceral obesity, insulin resistance, dyslipidemia, and hypertension. The criteria for diagnosing metabolic syndrome differ among ethnic groups, due in part to differences in eating habits and body build. Little is known about the relationship between metabolic syndrome and ischemic stroke in Asian countries. The aim of this study was to investigate the relationship between metabolic syndrome and first-time ischemic strokes. SUBJECTS & METHODS: Study subjects were 1,493 Japanese adults aged 55 years-old or older with no diabetes mellitus, no history of stroke and no neurological abnormalities, who participated in a voluntary neurological health screening at the Institute of Shimane Health Science, Japan (767 men, 62.0 +/- 5.9 years old at entry and 726 women, 61.8 +/- 5.1 years old at entry). All subjects were given an annual clinical stroke questionnaire. Clinical details of patients who reported strokes were confirmed with the attending physicians. Each subject was evaluated for an average of 6.4 +/- 3.8 years. Metabolic syndrome was defined using the modified criteria for Japanese population published in April 2005. RESULTS: Metabolic syndrome was diagnosed in 11.0% of men and 1.1% of women. Adjusting for age and smoking, female subjects with metabolic syndrome had a 23.1-fold increased risk of suffering ischemic strokes [95% confidence interval (CI), 2.7-196], whereas metabolic syndrome did not increase the risk of ischemic stroke in men. CONCLUSIONS: Metabolic syndrome is more likely to influence a risk for ischemic stroke in women than in men.

Differentiating Alzheimer's disease from subcortical vascular dementia with the FAB test.

BACKGROUND: The frontal assessment battery (FAB) test is a composite tool for assessing executive functions related to the frontal lobe. Neuropsychological and blood-flow studies indicate distinct patterns of deterioration of anterior and posterior cortical function in Alzheimer's disease (AD) and subcortical vascular dementia (VD) patients. We predict that the FAB score may be useful for discriminating VD from AD. OBJECTIVE: To evaluate the clinical usefulness of the FAB test for differential diagnosis of AD and VD. METHODS: We compared FAB scores in 25 patients with AD, 27 patients with VD, and 80 age-matched normal control subjects. The AD group was matched for age, education and MMSE score with the VD group. The subtest scores in FAB were also compared among the three groups. RESULTS: The FAB scores were significantly decreased in both the AD and VD groups compared to the control group, and the reduction were greater in the VD group. Among the FAB subtests, mental flexibility (phonological verbal fluency) was the only subtest that significantly discriminated VD from the other two groups. CONCLUSIONS: The FAB test can provide useful information for differentiating AD and VD at the bedside.