Superficial small cerebellar infarcts in cerebral amyloid angiopathy on 3 T MRI: A preliminary study.

BACKGROUND: Strictly superficial cerebellar microbleeds and cerebellar superficial siderosis have been considered markers of advanced cerebral amyloid angiopathy (CAA), but there are few studies on cerebellar ischemic lesions in CAA. We investigated the presence of superficial small cerebellar infarct (SCI) ≤15 mm and its relation to magnetic resonance imaging (MRI) markers in patients with probable CAA. METHODS: Eighty patients with probable CAA were retrospectively evaluated. The presence of superficial SCIs was examined, along with cerebellar microbleeds and cerebellar superficial siderosis, using 3-T MRI. Lobar cerebral microbleeds, cortical superficial siderosis (cSS), enlargement of the perivascular space in the centrum semiovale, and white matter hyperintensity were assessed and the total CAA-small vessel disease (SVD) score was calculated. RESULTS: Nine of the 80 patients (11.3%) had a total of 16 superficial SCIs. By tentatively defining SCI <4 mm as cerebellar microinfarcts, 8 out of 16 (50%) superficial SCIs corresponded to cerebellar microinfarcts. The total CAA-SVD score was significantly higher in patients with superficial SCIs (p = 0.01). The prevalence of cSS (p = 0.018), cortical cerebral microinfarct (p = 0.034), and superficial cerebellar microbleeds (p = 0.006) was significantly higher in patients with superficial SCIs. The number of superficial cerebellar microbleeds was also significantly higher in patients with superficial SCIs (p = 0.001). CONCLUSIONS: Our results suggest that in patients with CAA, superficial SCIs (including microinfarcts) on MRI may indicate more severe, advanced-stage CAA. These preliminary findings should be verified by larger prospective studies in the future.

Magnetic resonance imaging and neuropsychological findings for predicting of cognitive deterioration in memory clinic patients.

Objective: The severity of cerebral small vessel disease (SVD) on magnetic resonance imaging (MRI) has been assessed using hypertensive arteriopathy SVD and cerebral amyloid angiopathy (CAA)-SVD scores. In addition, we reported the modified CAA-SVD score including cortical microinfarcts and posterior dominant white matter hyperintensity. Each SVD score has been associated with cognitive function, but the longitudinal changes remain unclear. Therefore, this study prospectively examined the prognostic value of each SVD score, imaging findings of cerebral SVD, and neuropsychological assessment. Methods: This study included 29 patients diagnosed with mild cognitive impairment or mild dementia at memory clinic in our hospital, who underwent clinical dementia rating (CDR) and brain MRI (3D-fluid attenuated inversion recovery, 3D-double inversion recovery, and susceptibility-weighted imaging) at baseline and 1 year later. Each SVD score and neuropsychological tests including the Mini-Mental State Examination, Japanese Raven's Colored Progressive Matrices, Trail Making Test -A/-B, and the Rivermead Behavioral Memory Test were evaluated at baseline and 1 year later. Results: Twenty patients had unchanged CDR (group A), while nine patients had worsened CDR (group B) after 1 year. At baseline, there was no significant difference in each SVD score; after 1 year, group B had significantly increased CAA-SVD and modified CAA-SVD scores. Group B also showed a significantly higher number of lobar microbleeds than group A at baseline. Furthermore, group B had significantly longer Japanese Raven's Colored Progressive Matrices and Trail Making test-A times at baseline. After 1 year, group B had significantly lower Mini-Mental State Examination, Japanese Raven's Colored Progressive Matrices, and Rivermead Behavioral Memory Test scores and significantly fewer word fluency (letters). Conclusion: Patients with worsened CDR 1 year after had a higher number of lobar microbleeds and prolonged psychomotor speed at baseline. These findings may become predictors of cognitive deterioration in patients who visit memory clinics.

Association between behavioral and psychological symptoms and cerebral small vessel disease MRI findings in memory clinic patients.

Objectives: Cerebral small vessel disease (SVD) is commonly observed among elderly individuals with cognitive impairment and has been recognized as a vascular contributor to dementia and behavioral and psychological symptoms (BPS), however, the relationship between BPS and SVD burden remains unclear. Methods: We prospectively recruited 42 patients with mild cognitive impairment (MCI) or mild dementia from the memory clinic in our hospital, who were assigned to either a clinical dementia rating (CDR) of 0.5 or 1.0, respectively. The presence of BPS was determined through interviews with caregivers. The patients underwent brain MRI and three types of SVD scores, total, cerebral amyloid angiopathy (CAA), and modified CAA, were assigned. Patients were also evaluated through various neuropsychological assessments. Results: The CDR was significantly higher in patients with BPS (p = 0.001). The use of antihypertensive agents was significantly higher in patients without BPS (p = 0.038). The time taken to complete trail making test set-A was also significantly longer in patients with BPS (p = 0.037). There was no significant difference in total SVD and CAA-SVD score (p = 0.745, and 0.096) and the modified CAA-SVD score was significantly higher in patients with BPS (p = 0.046). In addition, the number of total CMBs and lobar CMBs was significantly higher in patients with BPS (p = 0.001 and 0.001). Receiver operating characteristic curves for BPS showed that for modified CAA-SVD, a cutoff score of 3.5 showed 46.7% sensitivity and 81.5% specificity. Meanwhile, for the total number of cerebral microbleeds (CMBs), a cut-off score of 2.5 showed 80.0% sensitivity and 77.8% specificity and for the number of lobar CMBs, a cut-off score of 2.5 showed 73.3% sensitivity and 77.8% specificity. Conclusion: Overall, patients with BPS showed worse CDRs, reduced psychomotor speed, higher modified CAA-SVD scores, larger numbers of total and lobar CMBs. We propose that severe modified CAA scores and higher numbers of total and lobar CMBs are potential risk factors for BPS in patients with mild dementia or MCI. Therefore, by preventing these MRI lesions, the risk of BPS may be mitigated.

Cerebral Microbleeds With Atrial Fibrillation After Ablation Therapy.

BACKGROUND: The prevalence of cerebral microbleeds (CMBs) is significantly higher in patients with atrial fibrillation (AF) than in those without AF. CMBs in patients with AF have been reported to be primarily of the lobar type, but the exact cause of this remains unknown. We investigated the possibility that hemorrhagic transformation of embolic microinfarction can account for de novo lobar CMBs. METHODS: A total of 101 patients who underwent ablation therapy for AF were prospectively registered, and 72 patients completed the assessment with MRI 6 months after catheter ablation. Brain MRI, including diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI), were examined at 1-3 days (baseline) and 6 months after catheter ablation. We quantitatively evaluated the spatial and temporal distribution of embolic microinfarctions and de novo CMBs. RESULTS: Of the 101 patients, 68 were enrolled in this study. Fifty-nine patients (86.8%) showed embolic microinfarctions on baseline DWI immediately after catheter ablation. There were 137 CMBs in SWI, and 96 CMBs were of the lobar type. Six months later, there were 208 CMBs, including 71 de novo CMBs, and 60 of 71 (84.5%) were of the lobar type. Of the 71 de novo CMBs, 56 (78.9%) corresponded to the location of previous embolic microinfarctions found on baseline DWI. The platelet count was significantly lower and hematocrit/hemoglobin and Fazekas score were higher in the group with de novo CMBs than in the group without de novo CMBs. CONCLUSION: De novo CMBs frequently appeared after catheter ablation therapy. Our results suggest that embolic microinfarction can cause lobar CMBs.

Relationship of brain edema after deep brain stimulation surgery with motor and cognitive function.

Background: Some patients with Parkinson's disease (PD) develop peri-lead brain edema after deep brain stimulation (DBS) surgery. The influence of edema on neurological function is not well characterized. We investigated the relationship of brain edema after DBS surgery with motor and cognitive function. Methods: Thirteen patients with PD (6 males and 7 females; mean age: 61.2 years) who underwent bilateral subthalamic nucleus (STN) DBS surgery were included. All patients underwent magnetic resonance imaging (MRI) examination on day 6 post-DBS surgery. The volume of edema was measured either in the frontal white matter or STN on fluid attenuated inversion recovery (FLAIR) images. We examined the relationship between these volumes and changes in cognitive and motor function. Results: Patients were divided into those with frontal subcortical edema (FE) ≥3,000 mm3 (FE + group; n = 7) and <3,000 mm3 (FE-group; n = 6). In the FE + group, the postoperative Mini-Mental State Examination score worsened by 2.4 points after one week compared with that immediately before surgery, while that in the FE-group worsened only by 0.2 points (p = 0.038). On comparing patients with peri-STN edema (SE) ≥1,000 mm3 (SE + group; n = 3) and those with SE < 1,000 mm3 (SE-group; n = 10) showed that frequency of DBS tuning in the early postoperative period of the SE + group was lesser than that in the SE-group. Conclusions: Development of FE after DBS surgery was related to transient cognitive decline. On the other hand, SE seemed associated with altered motor function and reduces the requirement for tuning in the initial period after DBS implantation.

Correlation between Serum Zinc Levels and Levodopa in Parkinson's Disease.

Long-term intake of potential zinc-chelating drugs may cause zinc deficiency. We postulated that zinc deficiency in Parkinson's disease (PD) patients was related to the intake of drugs such as levodopa. We investigated the relationship between zinc levels and levodopa administration period, dosage, and symptoms of zinc deficiency in PD patients. We measured serum zinc levels and analyzed correlations between serum zinc levels, the levodopa oral administration period, dosage, dosing frequency, and zinc deficiency symptoms including taste disorders. Data analyses were performed using Spearman's rank correlation coefficient. The mean serum zinc level was 60.5 ± 11.6 µg/dL. The mean administration period for levodopa was 8.0 ± 5.5 years, mean administration frequency 3.4 ± 0.9 times/d, and mean administration dose 420.6 ± 237.1 mg/d. Negative correlations between zinc levels and levodopa dosage and dosing frequency were found. Multiple regression analysis showed a significant correlation with the frequency of levodopa (ß = -0.360, p = 0.007). No significant change in clinical symptoms was observed after zinc administration, but anxiety tended to improve. Our results indicated that frequent levodopa administration strongly influenced serum zinc levels which may have alleviating effects on psychiatric symptoms; therefore, preventing zinc deficiency can be important during PD treatment.

Brain magnetic resonance imaging and cognitive alterations after ablation in patients with atrial fibrillation.

Catheter ablation is an important non-pharmacological intervention for atrial fibrillation (AF), but its effect on the incidence of asymptomatic cerebral emboli and long-term effects on cognitive function remain unknown. We prospectively enrolled 101 patients who underwent AF ablation. Brain magnetic resonance imaging (MRI) (72 patients) and neuropsychological assessments (66 patients) were performed 1-3 days (baseline) and 6 months after ablation. Immediately after ablation, diffusion-weighted MRI and 3-dimensional double inversion recovery (3D-DIR) detected embolic microinfarctions in 63 patients (87.5%) and 62 patients (86.1%), respectively. After 6 months, DIR lesions disappeared in 41 patients. Microbleeds (MBs) increased by 17%, and 65% of the de novo MBs were exactly at the same location as the microinfarctions. Average Mini-Mental State Examination scores improved from 27.9 ± 2.4 to 28.5 ± 1.7 (p = 0.037), and detailed neuropsychological assessment scores showed improvement in memory, constructional, and frontal lobe functions. Ejection fraction, left atrial volume index and brain natriuretic peptide level improved from baseline to 3-6 months after ablation. Despite incidental microemboli, cognitive function was preserved 6 months after ablation.

PLA2G6 variants associated with the number of affected alleles in Parkinson's disease in Japan.

This study aimed to evaluate genotype-phenotype correlations of Parkinson's disease (PD) patients with phospholipase A2 group V (PLA2G6) variants. We analyzed the DNA of 798 patients with PD, including 78 PD patients reported previously, and 336 in-house controls. We screened the exons and exon-intron boundaries of PLA2G6 using the Ion Torrent system and Sanger method. We identified 21 patients with 18 rare variants, such that 1, 9, and 11 patients were homozygous, heterozygous, and compound heterozygous, respectively, with respect to PLA2G6 variants. The allele frequency was approximately equal between patients with familial PD and those with sporadic PD. The PLA2G6 variants detected frequently were identified in the early-onset sporadic PD group. Patients who were homozygous for a variant showed more severe symptoms than those who were heterozygous for the variant. The most common variant was p.R635Q in our cohort, which was considered a risk variant for PD. Thus, the variants of PLA2G6 may play a role in familial PD and early-onset sporadic PD.

MEFV gene mutations in neuro-Behçet's disease and neuro-Sweet disease.

Mediterranean fever (MEFV) gene mutations are associated with familial Mediterranean fever (FMF). Recent studies have suggested that MEFV gene mutations may act as disease modifiers in neuro-Behçet's (NBD) disease and neuro-Sweet disease (NSD). We investigated MEFV genes and clinical features in 17 patients with NBD or NSD. MEFV gene mutations were frequently observed (70.6%). Headaches and exertional leg pain were associated with MEFV gene mutations (P < 0.05). Moreover, higher frequency of white matter lesions without sites predilection (P < 0.05) and non-parenchymal lesions (P < 0.05) were also observed. MEFV gene mutations may be associated with particular findings and lesion sites.

Proposition of zinc supplementation during levodopa-carbidopa intestinal gel treatment.

OBJECTIVES: Levodopa-carbidopa intestinal gel (LCIG) infusion is a useful therapy for the wearing-off phenomenon of advanced Parkinson's disease (PD) patients. Recently, we found three PD patients that may have had a zinc deficiency after the LCIG infusion, possibly due to the zinc-chelating action of levodopa. This study aims to evaluate changes in serum zinc levels in three patients that received LCIG treatment and to determine possible remedies for zinc deficiency during treatment. MATERIALS AND METHODS: We performed a prospective blood analysis of serum zinc levels before, when possible, and after LCIG treatment in our three PD patients. RESULTS: The serum zinc levels of the first patient before treatment and 4 months after beginning LCIG treatment were 69 and 58 µg/dl, respectively. For the second patient, serum zinc levels before treatment and two months after starting LCIG treatment were 87 and 46 µg/dl, respectively. The baseline serum zinc level for the third patient was not examined, but was 48 µg/dl 5 months after starting the LCIG infusion. CONCLUSIONS: Levodopa-carbidopa intestinal gel infusion might have caused a zinc deficiency through levodopa zinc chelation. Zinc deficiency with LCIG infusion has not yet been reported, though preventing zinc deficiency may be an important factor in future LCIG treatment strategies.

Large refractive index changes of a chemically amplified photoresist in femtosecond laser nonlinear lithography.

We found that marked increases in refractive index of chemically amplified photoresists induced by highly repetitive femtosecond laser irradiation without post-exposure baking treatment. For laser writing speed less than 30 µm/s, the refractive index change of the nonlinear absorption region was as large as 8 × 10(-3). Moreover, cross-linking reactions of the resists were induced. The refractive index changes can generate optical confinement and subsequent channel propagations of femtosecond laser pulses. The coupling efficiency was estimated as high as 87% using a low numerical aperture objective lens. The peak intensities of the guiding modes exceeded the polymerization threshold of the resist.

Comparative analysis of Micrococcus luteus isolates from blood cultures of patients with pulmonary hypertension receiving epoprostenol continuous infusion.

During the period 2002-2008, at the National Cardiovascular Center, Osaka, 28 Micrococcus luteus isolates and one Kocuria spp. isolate were obtained from blood cultures of pulmonary hypertension (PH) patients who were receiving continuous infusion therapy with epoprostenol. Pulsed-field gel electrophoresis patterns of the isolates were unrelated, suggesting that the infections had multiple origins. The preparation of epoprostenol solution by patients themselves was thought to be a risk factor.

SiO2-based nonplanar structures fabricated using femtosecond laser lithography.

SiO2-based hybrid diffractive-refractive microlenses were fabricated by femtosecond laser lithography-assisted micromachining, which is a combined process of nonlinear lithography and plasma etching. The high-aspect-ratio patterns of resist were formed by laser exposure without translating the laser spot. By scanning this rod three-dimensionally, micro-Fresnel lens patterns were written directly inside resists on the convex lenses. Then, the resist patterns were transferred to the underlying lenses by CHF(3) plasma. We obtained SiO2 nonplanar structures with smooth surfaces. This hybridization shifted the focal length of the lens by 216 microm, which was consistent with theoretical value.

Periodic structures consisting of germanium nanoparticles in buried channel waveguides.

Periodic structures consisting of Ge nanoparticles were formed in buried channel waveguides. Such periodic structures were created in GeO(2)-B(2)O(3)-SiO(2) thin glass films by the combination of exposure to interference patterns of ultraviolet laser light and thermally induced phase changes of the glasses. The periodic structures in the channels served as the Bragg gratings with high diffraction efficiencies in the optical communication wavelength. Transmission spectra measurements show the depths and positions of the diffraction peaks as 37.77 dB at 1536.2 nm and 38.72 dB at 1537.6 nm, respectively, for TE-like and TM-like modes. The diffraction efficiencies remain unchanged even after further annealing at temperatures as high as 500 degrees C.

Characterization and gene cloning of telomere-binding protein from tobacco BY-2 cells.

In this study, we performed gel mobility shift assays using tobacco BY-2 nuclei extracts to identify the plant telomere-binding proteins (TBP). Although no complexes were detected using C-strand as a probe, a single DNA-protein complex was detected using single-stranded 32P-(TTTAGGG)4 as a probe. In competition experiments, formation of the complex was inhibited only when an ssG-strand telomere repeat was used as a competitor. These results indicate that the observed band reflects a G-strand specific single-stranded telomere-binding protein (NtGTBP1). We purified the binding protein and subsequently used RT-PCR to isolate a gene encoding the protein. The sequence reveals that the protein (NtGTBP1) is a novel TBP from a higher plant, and a search for conserved domains showed that NtGTBP1 contains two RNA recognition motifs (RRMs).