Yusuke Nanri

Brain Microbleeds and Global Cognitive Function in Adults Without Neurological Disorder

Background and Purpose— Increasing attention has been paid to associations between cognitive dysfunction and brain microbleeds (MBs). Because all previous studies have investigated patients with neurological disorders, we examined subjects without neurological disorder in order to clarify pathogenic relationships. Methods— A total of 518 consecutive adults without neurological disorder who had undergone health-screening tests of the brain were studied prospectively. Gradient-echo T2*-weighted MRI using a 1.5-T system was used to detect MBs. The Mini-Mental State Examination (MMSE) was administered to determine cognitive functions. MMSE scores <27 or >1.5 SDs below the age-related mean were regarded as subnormal. Results— MBs were found in 35 subjects (6.8%). MMSE score <27 was found in 25 subjects (4.8%), with MMSE score >1.5 SDs below the age-related mean in 34 subjects (6.6%). Univariate analysis showed presence and number of MBs, short duration of education, and severe white matter hyperintensities as significantly associated with subnormal scores. In logistic regression analysis, presence of MBs (odds ratio [OR], 5.44; 95% CI, 1.83 to 16.19) and number of MBs (OR, 1.32; 95% CI, 1.04 to 1.68) still displayed significant associations with MMSE score <27. Logistic regression analysis revealed a significant relationship between presence (OR, 3.93; 95% CI, 1.44 to 10.74) and number (OR, 1.26; 95% CI, 1.01 to 1.59) of MBs and MMSE score >1.5 SDs below the age-related mean. Among MMSE subscores, “attention and calculation” was significantly lower in MB-positive subjects (P=0.017). Conclusions— MBs appear to be primarily associated with global cognitive dysfunction.

Distributional Impact of Brain Microbleeds on Global Cognitive Function in Adults Without Neurological Disorder

Background and Purpose— Brain microbleeds (MBs) are considered to be associated with cognitive decline and can be pathologically and topographically classified as cerebral amyloid angiopathy-related (located in lobar regions) and hypertensive microangiopathy-related (located in deep regions). We examined whether different effects on global cognitive function might be seen with different distributions of MBs. Methods— A total of 1279 adults without neurological disorders were studied prospectively. Subjects were divided into 4 groups: without-MBs group; lobar group; deep group; and with in both areas (diffuse group). The Mini-Mental State Examination was administered to determine global cognitive functions, with scores <27 regarded as subnormal. Results— MBs were detected in 98 subjects (8%): 36 subjects (3%) classified as lobar group, 48 subjects (4%) as deep group, and 14 subjects (1%) as diffuse group. Subnormal scores were found in 76 subjects (5.9%), associated with age, education, hypertension, severe white matter hyperintensities, and distribution and number of MBs. In the final model of logistic regression analysis, the deep group (OR, 2.79; 95% CI, 1.14–6.79) was associated with subnormal scores, whereas the lobar group (OR, 0.77; 95% CI, 0.17–3.44) was not. Trend for the diffuse group did not reach the level of significance (OR, 5.01; 95% CI, 0.88–28.41). These trends were also seen in analysis using another cut-off point for subnormal score. Scores for total Mini-Mental State Examination and attention and calculation were significantly lower in the deep group and the diffuse groups compared with the without-MBs group. Conclusions— This Japanese cross-sectional study demonstrated that MB-related global cognitive dysfunction seems to occur based on hypertensive pathogenesis rather than on cerebral amyloid angiopathy.

Topography and associations of perivascular spaces in healthy adults The Kashima Scan Study

Objective: We investigated whether the topography of MRI-visible perivascular spaces (PVS) is associated with markers of specific underlying small vessel disease, including cerebral microbleed (CMB) distribution, in neurologically healthy adults. Methods: We analyzed baseline data of an ongoing Japanese population-based cohort study. PVS were rated in the basal ganglia (BG-PVS) and centrum semiovale (CSO-PVS) on axial T2-weighted MRI using a validated rating scale (score 0–4). BG-PVS degree was classified as low (score <2) or high (score ≥2). CSO-PVS degree was classified as low (score <3) or high (score ≥3). Independent demographic, clinical, and imaging factors for high degree of BG-PVS and CSO-PVS were investigated. Results: A total of 1,575 neurologically healthy adults were included (mean age 57.1 years, SD 9.7; 47% male). In multivariable analyses, high degree of BG-PVS (n = 212, 14%) was associated with deep or infratentorial CMBs (odds ratio [OR] 2.77, 95% confidence interval [CI] 1.62–4.74), a marker of hypertensive arteriopathy; by contrast, high degree of CSO-PVS (n = 357, 23%) was associated with strictly lobar CMBs (OR 2.49, 95% CI 1.35–4.61), which share risk factors with cerebral amyloid angiopathy. Both high degree of BG-PVS and CSO-PVS were associated with hypertension (OR 2.03, 95% CI 1.46–2.82 and OR 1.39, 95% CI 1.07–1.81, respectively), lacunes (OR 3.35, 95% CI 1.92–5.86; OR 1.83 95% CI 1.08–3.08), and severe white matter hyperintensities (OR 2.17, 95% CI 1.42–3.31; OR 1.35, 95% CI 0.93–1.96), but these associations were stronger for high degree of BG-PVS. Conclusions: In a neurologically healthy cohort, the associations of PVS differ according to their topography. PVS distribution may be useful for the early detection and classification of small vessel disease.

Marked cerebral atrophy is correlated with kidney dysfunction in nondisabled adults.

The relationship between kidney dysfunction, such as chronic kidney disease (CKD), and brain morphology has attracted increasing attention, but the association between kidney dysfunction and cerebral atrophy has yet to be determined. The purpose of this study was to clarify the relationship between kidney function and a substantial degree of cerebral atrophy. A total of 610 consecutive Japanese adults without neurological disorders who had undergone health screening tests of the brain were studied prospectively. Magnetic resonance imaging was performed using a 1.5-T scanner. Using a computer-assisted processing system, the percentage of cerebrum atrophy (%Cerebrum atrophy) was calculated as an index of cerebral atrophy. Atrophy was defined as >2 s.d.s below the mean %Cerebrum atrophy. The glomerular filtration rate (GFR) was estimated using the revised equations for estimated GFR from serum creatinine in Japan. Kidney function variables included the GFR value and the prevalence of subjects with GFR <60 ml min−1 per 1.73 m2. Cerebral atrophy was found in 25 (4.1%) cases. Univariate analysis showed that age, male sex, hypertension, each kidney function variable, white matter hyperintensities and lacunae were associated with cerebral atrophy. On logistic regression analysis, GFR (odds ratio (OR), 0.64; 95% confidence interval (CI), 0.42–0.98) and GFR <60 ml min−1 per 1.73 m2 (OR, 5.93; 95% CI, 1.82–19.27) were significantly associated with cerebral atrophy. On sub-analysis, GFR <60 ml min−1 per 1.73 m2 was significantly associated with cortical atrophy (OR, 3.23; 95% CI, 1.15–9.11). Decreased GFR was significantly associated with cerebral atrophy, indicating that treatment of CKD may control age-related degenerative processes of the brain.

Identification of astrocyte-derived immune suppressor factor that induces apoptosis of autoreactive T cells

In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, apoptosis of T cells is mainly seen at inflammation sites of the central nervous system (CNS). Cumulative data suggests that astrocytes might render T cells susceptible to induction of apoptotic cell death. We observed that apoptotic cell death of proteolipid protein (PLP)-reactive T cells was induced by an interferon (IFN)-γ-treated astrocyte cell line. In this study, we have identified and cloned the genes derived from the IFN-γ-treated astrocyte cell line that induce apoptosis of autoreactive T cells. We created subtraction cDNA libraries from the IFN-γ-treated astrocyte cell line and obtained 100 positive clones. After screening of subtracted cDNAs, we found two candidate genes that induced apoptosis of the PLP-reactive T cell line. The first is a previously unknown gene of 726 base pairs that we named astrocyte-derived immune suppressor factor (AdIF). It contained an open reading frame encoding a polypeptide of 228 amino acids. The second was SPARC/osteonectin, a multifunctional glycoprotein secreted in the extracellular matrix. AdIF protein was found at the inflammatory sites of the EAE brain, and bound to the surface of CD4(+) T cells. Purified recombinant AdIF protein inhibited the proliferation of activated PLP-reactive CD4(+) T cells and induced their apoptosis in vitro. Intravenous administration of recombinant AdIF protein to mice with in which acute EAE was induced prevented the incidence of EAE and suppressed the symptoms. The newly discovered molecule AdIF may render auto-reactive T cells susceptible to the induction of apoptotic cell death and could potentially be a new therapeutic agent for multiple sclerosis.

Microvascular Decompression Surgery for Vertebral Artery Compression of the Medulla Oblongata: 3 Cases with Respiratory Failure and/or Dysphagia

BACKGROUND It is well known that brainstem dysfunction may be caused by vascular compression of the medulla oblongata (MO). However, only a limited number of reports have found microvascular decompression (MVD) surgery to be an effective treatment for symptomatic patients with MO dysfunction, such as essential hypertension, pyramidal tract signs, dysphagia, and respiratory failure. CASE DESCRIPTION This report describes 3 patients with vertebral artery compression of MO who presented with respiratory failure and/or dysphagia. MVD surgery using the transcondylar fossa approach was effective in relieving patient symptoms. CONCLUSIONS Although the pathogenic mechanisms of symptomatic vertebral artery compression of MO remain unclear, we should recognize that MVD surgery is effective for selected patients with brainstem dysfunction. The transcondylar fossa approach and the stitched sling retraction technique are appropriate in MVD surgery to relieve vertebral artery compression of MO.

Stroke Scale Items Associated with Neurologic Deterioration within 24 Hours after Recombinant Tissue Plasminogen Activator Therapy

It is unclear when and which neurologic deficits should be examined within 24 hours after intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke. Relationships between serial changes in National Institutes of Health Stroke Scale (NIHSS) subscores and neurologic deterioration (ND) within the first 24 hours after therapy were investigated in 43 consecutive patients. The NIHSS score was measured by neurologists 28 times within 24 hours after therapy. Assessments of subscores associated with ND, defined as the first change 4 or more points from baseline, were performed at 15 minutes (most frequent time of the first ND), 120 minutes (median time of the first ND), and 24 hours after therapy. Seventeen of 43 patients (age range, 55-94 years) showed ND. Of the NIHSS subscores, increases in scores for loss of consciousness (15 minutes, P = .001; 120 minutes, P = .026; 24 hours, P = .018) and motor limbs total (15 minutes, P = .014; 120 minutes, P = .031) were related to deterioration. Items such as questions, gaze, visual fields, ataxia, language, dysarthria, and extinction/inattention were not related to deterioration at any time. In conclusion, ND of ischemic stroke patients treated with intravenous rt-PA therapy was frequently seen within 120 minutes after therapy. Items such as loss of consciousness and motor limbs total may be considered indices for monitoring neurologic deficits after therapy.

Total Small Vessel Disease Score in Neurologically Healthy Japanese Adults in the Kashima Scan Study

Objective We explored the association between the total small vessel disease (SVD) score obtained with magnetic resonance imaging and risk factors and outcomes in the Japanese population. Methods The presence of SVD features, including lacunes, cerebral microbleeds, white matter changes, and basal ganglia perivascular spaces on MRI, was summed to obtain a “total SVD score” (range 0-4). Ordinal and multinomial logistic regression analyses were performed to investigate the association of higher total SVD scores with vascular risk factors, the Mini-Mental State Examination (MMSE) score, and cerebral atrophy. Results We included 1,451 neurologically healthy adults (mean age, 57.1 years; 47% male). A multivariate ordinal logistic regression analysis showed that the total SVD score was associated with aging, hypertension, blood pressure (BP), diabetes mellitus, MMSE score, and deep cerebral atrophy, but the equal slopes assumption between scores did not hold. A multivariate multinomial logistic regression analysis (total SVD score 0=reference) showed that aging, hypertension, and BP were positively associated with scores of 1, 2, or ≥3. These effects, presented as odds ratios (ORs), increased as the score increased and were strongest with a score of ≥3 [aging (per 10-year increment), OR 4.00, 95% confidence interval (CI) 2.47-6.46; hypertension, OR 5.68, 95% CI 2.52-12.80; systolic BP (per standard deviation increase), OR 1.96, 95% CI 1.41-2.74, respectively]. Diabetes mellitus and deep cerebral atrophy tended to be associated with the SVD scores. The MMSE score showed no consistent associations. Conclusion The total SVD score may be a promising tool for indexing SVD, even in the Japanese population.

Teaching NeuroImages:Simultaneous angiography and ultrasonography in extracranial internal carotid artery dissection

A 26-year-old woman was admitted with amaurosis fugax in the left eye and transient aphasia. Diffusion-weighted MRI revealed a small infarction in the left insular cortex. Transoral carotid ultrasonography (TOCU)1 demonstrated left ICA dilatation with narrowing of the true lumen and intramural mass (figure 1A), which was consistent …