Aiko Tamura

Characteristics of intracranial branch atheromatous disease and its association with progressive motor deficits

BACKGROUND Small deep brain infarcts are often caused by two different vascular pathologies: 1. atheromatous occlusion at the orifice of large caliber penetrating arteries termed branch atheromatous disease (BAD) and 2. lipohyalinotic degenerative changes termed lipohyalinotic degeneration (LD). We herein analyze and describe the characteristics of these 2 different pathologies. METHODS We studied 394 patients with penetrating artery territory infarcts in the territories of the lenticulostriate arteries and anterior pontine arteries. Radiologically defined BAD of the lenticulostriate arteries was defined as infarcts with size more than 10mm in diameter on axial slice and visible for 3 or more axial slices, and that of the anterior pontine arteries was defined as unilateral infarcts extending to the basal surface of the pons. Within each of the 2 territory groups, differences between BAD and LD were compared. RESULTS Ninety five patients in the lenticulostriate arteries group (36.1%) and 78 patients in anterior pontine arteries group (59.5%) were classified as BAD. Initial NIHSS, incidence of progressive motor deficits and poor functional outcome were significantly higher and incidence of concomitant silent lacunar infarcts tended to be lower in BAD than LD. In logistic regression analysis, BAD compared with LD was independently associated with PMD, in lenticulostriate arteries group (OR: 4.21, p=0.0001) and in anterior pontine arteries group (OR: 5.32, p=0.0018). CONCLUSIONS Radiologically defined BAD and LD had different characteristics. BAD was significantly associated with progressive motor deficits and considered as a major vascular mechanism of progressive motor deficits in penetrating artery infarcts.

Predictive factors for progressive motor deficits in penetrating artery infarctions in two different arterial territories

BACKGROUND Progressive motor deficits (PMD) are common in cerebral penetrating artery disease (PAD) during the acute stage and leads to severe disability. Reliable predictors and stroke mechanism for PMD in PAD have been yet to be elucidated. Moreover, difference of predictors between topographically classified PAD has not ever been systematically studied. METHODS Three hundred ninety two consecutive patients with acute PAD (<20 mm) who showed lacunar motor syndrome and admitted within 24 h after onset were selected for this study. Patients were divided into 2 groups whose infarcts were topographically located within the territories of lenticulostriate arteries (LSA), and anterior pontine arteries (APA). Within each of the 2 groups, factors associated with PMD were analyzed. RESULTS Progressive motor deficits were found in 55 patients (21.0%) in LSA group and 38 patients (29.0%) in APA group. In multivariate analysis, female sex and severity of motor deficit on admission (NIHSS 5 or more) were common independent predictors for PMD in both groups. The specific predictors were single infarcts without concomitant silent lacunar infarcts and preceding TIAs in LSA group and diabetes mellitus in APA group. CONCLUSIONS Predictive factors for PMD were different in the 2 different territory groups. Diabetes mellitus was particularly associated with PMD in APA group.

The infarct location predicts progressive motor deficits in patients with acute lacunar infarction in the lenticulostriate artery territory

BACKGROUND AND PURPOSE Patients with acute lacunar infarction in the lenticulostriate artery (LSA) territory often show progression of motor deficits (PMD) after admission. The purpose of our study is to identify predictors for PMD using the findings of diffusion-weighted imaging (DWI) on admission. METHODS From January 2005 to December 2008, we studied 60 consecutive patients with acute lacunar infarction in the LSA territory within 24h after onset. To identify predictors for PMD, clinical characteristics including vascular risk factors and DWI findings were evaluated. DWI findings included the size and location of the infarcts and the slice numbers of infarcts visible on DWI. For the location, posterior type was defined as an infarct located in the posterior part of corona radiata on the second slice from the top among slices including corona radiata. RESULTS Twenty-six patients (43%) showed PMD. In univariate analysis, age >or=75 (P=0.03), female sex (P=0.04), infarct slice number >or=3 (P=0.04), and posterior type infarct (P<0.001) were more frequent in the PMD group than in the no PMD group. In multivariate analysis, posterior type infarct was the only independent predictor among DWI findings for PMD (odds ratio, 14.83; 95% confidence interval, 3.54-87.21, P<0.001). CONCLUSIONS Posterior type infarct was the independent predictor in DWI findings for PMD in patients with lacunar infarction in the LSA territory. We postulate that the posterior type infarct may affect the corticospinal tract to a greater degree and cause PMD.

Relationship between Cnm‐positive Streptococcus mutans and cerebral microbleeds in humans

OBJECTIVE Cerebral hemorrhage has been shown to occur in animals experimentally infected with Streptococcus mutans carrying the collagen-binding Cnm gene. However, the relationship between cerebral microbleeds and oral hygiene, with a focus on Cnm gene-positive S. mutans infection, remains unclear. MATERIAL AND METHODS One hundred and thirty-nine subjects participated. The presence or absence of Cnm-positive S. mutans and its collagen-binding activity were investigated using saliva samples, and relationship with cerebral microbleeds detected on MRI investigated, including clinical information and oral parameters. RESULTS Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm-positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors. CONCLUSIONS The occurrence of cerebral microbleeds was higher in subjects carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S. mutans increases cerebral microbleeds, and is an independent risk for the development of cerebrovascular disorders.

The Relationship between Neurological Worsening and Lesion Patterns in Patients with Acute Middle Cerebral Artery Stenosis

Background: Intracranial atherosclerotic disease is one of the most common causes of ischemic stroke especially in Asians, Hispanics and blacks. Although middle cerebral artery (MCA) stenosis is increasingly being recognized with the advent of magnetic resonance angiography (MRA) or transcranial Doppler ultrasonography, few studies have focused on acute neurological worsening (NW) in patients with MCA stenosis. We investigated the relationship between NW and lesion patterns detected by diffusion-weighted imaging (DWI). Methods: We studied 44 consecutive patients out of a total of 2,863 consecutive patients who had symptomatic lesions in the territory of the MCA and in whom MRA and/or conventional angiography showed isolated MCA stenosis ≥50% in the MCA trunk. Acute DWI lesion patterns were classified as follows: (1) pial artery territory infarcts (PAI); (2) small cortical and/or subcortical infarcts (SCS); (3) deep penetrating artery territory infarcts (DPI); (4) cortical border zone infarcts (CBZ), and (5) internal border zone infarcts (IBZ). NW was defined as worsening by ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) during the first 7 days. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months after stroke onset. Poor outcome was defined as ≥3 on the mRS. The severity of MCA stenosis on MRA was further categorized as 50-75% (moderate) and >75% or focal signal loss with the presence of distal MCA signal (severe). Results: There were 14 patients (31.8%) who showed NW and 16 patients (36.3%) who showed poor outcomes. Nine of the 14 patients with NW showed poor outcomes (64.2%). The most frequent lesions in the present study were SCS (n = 16, 36.3%), followed by IBZ (n = 12, 27.2%) and DPI (n = 11, 25.0%). Prevalence of IBZ was significantly higher in the group with NW compared to that without NW (p = 0.0081), while the prevalence of SCS, DPI, PAI and CBZ did not differ between the two groups. Logistic regression analysis showed significantly high age- and sex-adjusted odds ratios (ORs) for NW only for IBZ (OR 10.9, p = 0.0051). The degree of stenosis did not correlate with NW and lesion patterns. Conclusions: Only IBZ among various lesion patterns correlated strongly with NW. IBZ are considered to be more associated with hemodynamic compromise, while embolic pathogeneses contribute more to CBZ or SCS. Early interventional medical treatments such as thrombolytic or anti-platelet therapy or stenting should be considered in cases of IBZ in MCA stenosis.

Oral Cnm - positive Streptococcus Mutans Expressing Collagen Binding Activity is a Risk Factor for Cerebral Microbleeds and Cognitive Impairment

Cerebral microbleeds (CMBs) are an important risk factor for stroke and dementia. We have shown that the collagen binding surface Cnm protein expressed on cnm-positive Streptococcus mutans is involved in the development of CMBs. However, whether the collagen binding activity of cnm-positive S. mutans is related to the nature of the CMBs or to cognitive impairment is unclear. Two-hundred seventy nine community residents (70.0 years) were examined for the presence or absence of cnm-positive S. mutans in the saliva by PCR and collagen binding activity, CMBs, and cognitive function were evaluated. Cnm-positive S. mutans was detected more often among subjects with CMBs (p < 0.01) than those without. The risk of CMBs was significantly higher (odds ratio = 14.3) in the group with S. mutans expressing collagen binding activity, as compared to the group without that finding. Deep CMBs were more frequent (67%) and cognitive function was lower among subjects with cnm-positive S. mutans expressing collagen binding activity. This work supports the role of oral health in stroke and dementia and proposes a molecular mechanism for the interaction.

Cognitive impairment and cerebral hypoperfusion in a CADASIL patient improved during administration of lomerizine.

A 64-year-old woman was admitted to our hospital for recurrent stroke and cognitive impairment and was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Iodine-123 iodoamphetamine single photon emission computed tomography showed hypoperfusion in the whole brain, but cerebral blood flow increased dramatically after the administration of acetazolamide in the cerebral cortex. Lomerizine, a diphenylmethylpiperazine Ca2+ channel blocker, can selectively increase cerebral blood flow. Cognitive decline and cerebral hypoperfusion improved during 2-year administration of lomerizine in this CADASIL patient, and thus, lomerizine is a potential candidate for treating cognitive impairment in CADASIL patients.

Ventricular Temperatures in Idiopathic Normal Pressure Hydrocephalus (iNPH) Measured with DWI-based MR Thermometry.

PURPOSE The brain produces intense heat as a result of cerebral metabolism and cerebral blood flow, and the generated heat is removed mainly through circulation of the intracranial blood vessels and cerebrospinal fluid (CSF). Because magnetic resonance (MR) images are constructed from analysis of the spin of various molecules, the diffusion coefficient can be used as a parameter that reflects the temperature of water molecules. We used diffusion-weighted imaging (DWI)-based MR imaging to measure the temperature of the CSF around the lateral ventricles in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS Our study included 33 cases of iNPH (Group N, mean age, 75.1 years) and 40 age-matched controls (Group C, mean age, 74.5 years). We calculated CSF temperature in the ventricular domain using the conversion formula to evaluate the feasibility of iNPH study. RESULTS The mean temperatures were significantly higher in Group N (37.6°C ± 0.4°C) than Group C (36.7°C ± 0.5°C; P < 0.01). The cut-off value of 37.2°C (more than the mean + 2 standard deviations [SD] of the values in Group C) showed sensitivity of 72.4% and specificity of 77.5% for distinguishing the 2 groups. We confirmed improved CSF temperature in the lateral ventricles in all patients examined both before and after shunting. CONCLUSIONS Elevated ventricular temperatures in patients with iNPH (Group N) may represent a disturbance in heat balance. Our results showed that thermometry using DWI-based MR imaging can help in the noninvasive and consistent evaluation of CSF temperature and may thus provide a useful supplementary brain biomarker for iNPH.

Serum albumin to globulin ratio is related to cognitive decline via reflection of homeostasis: a nested case-control study

BackgroundRecent research suggests that several pathogenetic factors, including aging, genetics, inflammation, dyslipidemia, diabetes, and infectious diseases, influence cognitive decline (CD) risk. However, no definitive candidate causes have been identified. The present study evaluated whether certain serum parameters predict CD.MethodsA total of 151 participants were assessed for CD using the Mini-Mental State Examination (MMSE), and 34 participants were identified as showing CD.ResultsAmong CD predictive risk factors, Helicobacter pylori seropositivity was significantly predictive of CD risk, more so than classical risk factors, including white matter lesions and arterial stiffness [adjusted odds ratio (OR) = 4.786, 95% confidence interval (CI) = 1.710–13.39]. A multivariate analysis indicated that the albumin to globulin (A/G) ratio was the only factor that significantly lowered CD risk (OR = 0.092, 95% CI = 0.010–0.887). A/G ratio also was positively correlated with MMSE scores and negatively correlated with disruption of homeostatic factors (i.e., non-high-density lipoprotein, hemoglobin A1c, and high-sensitive C-reactive protein).ConclusionsThe current study results suggest that the A/G ratio is related to cognitive decline and may reflect homeostatic alterations.

Association between α-Klotho and Deep White Matter Lesions in the Brain: A Pilot Case Control Study Using Brain MRI

BACKGROUND The anti-aging protein, α-Klotho, may be involved in cognitive decline and has potential as a surrogate marker that reflects dementia. However, the role of α-Klotho in the brain has not been sufficiently investigated. OBJECTIVE Here, we investigated the association between α-Klotho and cognitive decline that is associated with cerebral deep white matter lesions (DWMLs). METHODS Two hundred-eighty participants (187 males and 93 females, mean age: 70.8 years old) were evaluated for DWMLs, and the Fazekas scale (Grade) was assessed following brain magnetic resonance imaging. A questionnaire concerning lifestyle and neuropsychological tests was administered, and their associations with the blood α-Klotho level were retrospectively investigated. RESULTS The α-Klotho level was 685.1 pg/mL in Grade 0 (68 subjects), 634.1 in G1 (134), 596.0 in G2 (62), and 571.6 in G3 (16), showing that the level significantly decreased with advanced grades. Significant correlations were noted between the α-Klotho level and higher brain function tests including the Mini-Mental State Examination and word fluency tests (p < 0.05). When a 90th percentile value of the level in the G0 group (400 pg/mL) or lower was defined as a low α-Klotho level, the odds ratio of the high-grade G3 group was 2.9 (95% confidence interval: 1.4-7.8) (after correction for age, sex, hypertension, and chronic kidney disease), which was significant. CONCLUSION A reduced blood α-Klotho level was correlated with grading of cerebral DWMLs and was accompanied by cognitive decline as an independent risk factor. The α-Klotho level may serve as a useful clinical index of vascular cognitive impairment.