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To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive association (P= 6.5 × 10−7) that was replicated in additional Japanese samples (P= 2.9 × 10−6. OR = 1.58; 95% confidence interval, 1.30 to 1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data (P= 5.0 × 10-15. Odds ratio= 1.49; 95% CI 1.35 to 1.72). The association of rs2303744 with MSA remained significant in combined European/North American samples (P=0.023. Odds ratio=1.14; 95% CI 1.02 to 1.28) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution inPLA2G4Cthat encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform that may perturb membrane phospholipids and α-synuclein biology.

Objectives A pre-possible multiple system atrophy (MSA) phase, that is, the period between symptom onset and satisfying the second consensus diagnostic criteria for possible or probable MSA, may exist. The aim of the study was to identify the pre-possible MSA phase and to pursue the earlier diagnosis of MSA. Materials & methods We reviewed 52 patients with a clinical diagnosis of MSA and 430 patients showing any signs of parkinsonism, sporadic cerebellar ataxia, or autonomic failure with other clinical diagnoses. Results The pre-possible MSA phase was noted in 35 patients with a clinical diagnosis of MSA and 13 patients with other clinical diagnoses. During this phase, 16 patients presented with autonomic features first, while they presented later in 32 patients. Between these patients, there was no significant difference regarding parkinsonian, cerebellar features, levodopa response, or Babinski sign with hyperreflexia. Comparisons by autonomic features or autonomic function tests could not be performed due to the small number of patients. "Atrophy on magnetic resonance imaging of the putamen, middle cerebellar peduncle, pons, or cerebellum" and "new or increased snoring" showed high positive predictive values for MSA. Conclusion A pre-possible MSA phase exists. Improved earlier diagnosis of MSA depends on the sensitivity and positive predictive value of autonomic features or autonomic function tests and on the sensitivity of "atrophy on magnetic resonance imaging of the putamen, middle cerebellar peduncle, pons, or cerebellum" and "new or increased snoring" during the pre-possible MSA phase.

Background and Aim Early clinical diagnosis of progressive supranuclear palsy (PSP) remains challenging. Aim We attempted to identify any sign or symptom to diagnose PSP earlier. Methods A total of 401 patients, 40 with PSP and 361 with other neurodegenerative disorders, were included. We followed these patients for at least 1 year since 2009. We reviewed the signs and symptoms of patients with PSP in a standardized manner, and observed four manifestations: “vertical supranuclear gaze abnormality,” “movement disorders,” “pseudobulbar palsy” and “dementia of frontal type.” Features, such as symmetric parkinsonism, freezing of gait, postural instability, dysarthria and/or dysphagia, or dementia of frontal type, were considered core clinical features. Results In patients with PSP, “movement disorders” was the most common manifestation, whereas “vertical supranuclear gaze abnormality” was uncommon during the early disease course. A total of 16 patients fulfilled the National Institute for Neurological Disorders and Stroke and Society for PSP criteria for possible PSP at their first clinic visit. Of the remaining 24 patients, 15 presented with one or more core clinical features before fulfilling the criteria for possible PSP; nine patients had a clinical diagnosis of PSP but never fulfilled the criteria. A total of 49 of the 361 patients with other neurodegenerative disorders had core clinical features. A comparison showed that freezing of gait differentiated the groups the best over the disease course. Conclusion Freezing of gait is an early feature that might improve the clinical diagnosis of PSP, whereas vertical supranuclear gaze abnormality is not.

Objective To identify mutations in vacuolar protein sorting 13A (VPS13A) for Japanese patients with suspected chorea-acanthocytosis (ChAc). Methods We performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis of the VPS13A gene, and chorein Western blotting of erythrocyte ghosts. As the results of the analysis, 17 patients were molecularly diagnosed with ChAc. In addition, we investigated the distribution of VPS13A gene mutations and clinical symptoms in a total of 39 molecularly diagnosed Japanese patients with ChAc, including 22 previously reported cases. Results We identified 11 novel pathogenic mutations, including 1 novel CNV. Excluding 5 patients with the unknown symptoms, 97.1% of patients displayed various neuropsychiatric symptoms or forms of cognitive dysfunction during the course of disease. The patients carrying the 2 major mutations representing over half of the mutations, exon 60–61 deletion and exon 37 c.4411C>T (R1471X), were localized in western Japan. Conclusions We identified 13 different mutations in VPS13A, including 11 novel mutations, and verified the clinical manifestations in 39 Japanese patients with ChAc.

The aim of the present study was to compare the efficacy of magnetic resonance imaging (MRI) and 123I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane single photon emission computed tomography (123I-FP-CIT SPECT) for determining the clinical severity of patients with multiple system atrophy with Parkinsonism (MSA-P). MRI and 123I-FP-CIT SPECT images from 17 patients with MSA-P as diagnosed using the Unified MSA Rating Scale part IV (UMSARS IV) score were compared. Brain MRI scans were available for all 17 patients and 123I-FP-CIT SPECT images were available for 12 patients. Putaminal atrophy (PA), hyperintense putaminal rim (HPR), hyperintense pons (hot cross bun sign, HCB), atrophy of the cerebellar vermis and hemisphere (cerebellar atrophy, CA) and other abnormalities were evaluated in the MRI scans. Distribution of striatal uptake (SU) and the specific binding ratio (SBR) on each side of the bilateral striatum were evaluated using 123I-FP-CIT SPECT images. No significant associations were observed between HPR, HCB, CA and UMSARS IV score. However, the frequency of PA increased significantly with higher UMSARS IV score (P

The aim of the present study was to compare the efficacy of magnetic resonance imaging (MRI) and 123I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)nortropane single photon emission computed tomography (123I-FP-CIT SPECT) for determining the clinical severity of patients with multiple system atrophy with Parkinsonism (MSA-P). MRI and 123I-FP-CIT SPECT images from 17 patients with MSA-P as diagnosed using the Unified MSA Rating Scale part IV (UMSARS IV) score were compared. Brain MRI scans were available for all 17 patients and 123I-FP-CIT SPECT images were available for 12 patients. Putaminal atrophy (PA), hyperintense putaminal rim (HPR), hyperintense pons (hot cross bun sign, HCB), atrophy of the cerebellar vermis and hemisphere (cerebellar atrophy, CA) and other abnormalities were evaluated in the MRI scans. Distribution of striatal uptake (SU) and the specific binding ratio (SBR) on each side of the bilateral striatum were evaluated using 123I-FP-CIT SPECT images. No significant associations were observed between HPR, HCB, CA and UMSARS IV score. However, the frequency of PA increased significantly with higher UMSARS IV score (P

International audience; Objective : Glucocerebrosidase gene (GBA) variants that cause Gaucher disease are associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB). To investigate the role of GBA variants in multiple system atrophy (MSA), we analyzed GBA variants in a large case–control series.Methods : We sequenced coding regions and flanking splice sites of GBA in 969 MSA patients (574 Japanese, 223 European, and 172 North American) and 1509 control subjects (900 Japanese, 315 European, and 294 North American). We focused solely on Gaucher-disease-causing GBA variants.Results : In the Japanese series, we found nine carriers among the MSA patients (1.65%) and eight carriers among the control subjects (0.89%). In the European series, we found three carriers among the MSA patients (1.35%) and two carriers among the control subjects (0.63%). In the North American series, we found five carriers among the MSA patients (2.91%) and one carrier among the control subjects (0.34%). Subjecting each series to a Mantel–Haenszel analysis yielded a pooled odds ratio (OR) of 2.44 (95% confidence interval [CI], 1.14–5.21) and a P-value of 0.029 without evidence of significant heterogeneity. Logistic regression analysis yielded similar results, with an adjusted OR of 2.43 (95% CI 1.15–5.37) and a P-value of 0.022. Subtype analysis showed that Gaucher-disease-causing GBA variants are significantly associated with MSA cerebellar subtype (MSA-C) patients (P = 7.3 × 10−3).Interpretation : The findings indicate that, as in PD and DLB, Gaucher-disease-causing GBA variants are associated with MSA.

ObjectiveTo identify mutations in vacuolar protein sorting 13A (VPS13A) for Japanese patients with suspected chorea-acanthocytosis (ChAc).MethodsWe performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis of the VPS13A gene, and chorein Western blotting of erythrocyte ghosts. As the results of the analysis, 17 patients were molecularly diagnosed with ChAc. In addition, we investigated the distribution of VPS13A gene mutations and clinical symptoms in a total of 39 molecularly diagnosed Japanese patients with ChAc, including 22 previously reported cases.ResultsWe identified 11 novel pathogenic mutations, including 1 novel CNV. Excluding 5 patients with the unknown symptoms, 97.1% of patients displayed various neuropsychiatric symptoms or forms of cognitive dysfunction during the course of disease. The patients carrying the 2 major mutations representing over half of the mutations, exon 60–61 deletion and exon 37 c.4411C>T (R1471X), were localized in western Japan.ConclusionsWe identified 13 different mutations in VPS13A, including 11 novel mutations, and verified the clinical manifestations in 39 Japanese patients with ChAc.

Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system atrophy is widely considered to be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement of genetic components.In combination with linkage analysis, we performed whole-genome sequencing of a sample obtained from a member of a multiplex family in whom multiple-system atrophy had been diagnosed on autopsy. We also performed mutational analysis of samples from members of five other multiplex families and from a Japanese series (363 patients and two sets of controls, one of 520 persons and one of 2383 persons), a European series (223 patients and 315 controls), and a North American series (172 patients and 294 controls). On the basis of these analyses, we used a yeast complementation assay and measured enzyme activity of parahydroxybenzoate-polyprenyl transferase. This enzyme is encoded by the gene COQ2 and is essential for the biosynthesis of coenzyme Q10. Levels of coenzyme Q10 in lymphoblastoid cells and brain tissue were measured on high-performance liquid chromatography.We identified a homozygous mutation (M78V-V343A/M78V-V343A) and compound heterozygous mutations (R337X/V343A) in COQ2 in two multiplex families. Furthermore, we found that a common variant (V343A) and multiple rare variants in COQ2, all of which are functionally impaired, are associated with sporadic multiple-system atrophy. The V343A variant was exclusively observed in the Japanese population.Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease, providing evidence of a role of impaired COQ2 activities in the pathogenesis of this disease. (Funded by the Japan Society for the Promotion of Science and others.).

Key wrapping schemes are used to encrypt data of high entropy, such as cryptographic keys. There are two known security definitions for key wrapping schemes. One captures the security against chosen plaintext attacks (called DAE-security), and the other captures known plaintext attacks (called AKW-security). In this paper, we revisit the security of Hash-then-CBC key wrapping schemes. At SKEW 2011, Osaki and Iwata showed that the U CC -then-CBC key wrapping scheme, a key wrapping scheme that uses the U CC hash function and the CBC mode, has provable AKW-security. In this paper, we show that the scheme achieves the stronger notion of DAE-security. We also show our proof in the variable input length setting, where the adversary is allowed making queries of varying lengths. To handle such a setting, we generalize the previous definition of the U CC hash function to the variable input length setting, and show an efficient construction that meets the definition. We next consider linear-then-CBC, 2nd-preimage-resistant-then-CBC, and universal-then-CBC schemes. At SAC 2009, Gennaro and Halevi noted that these schemes do not achieve DAE-security. However, details were not presented, and we show concrete and efficient chosen plaintext attacks on these schemes, and confirm that they do not achieve DAE-security.

Constructing a secure and efficient key wrapping scheme is demanding, and the scheme based on a universal hash function and an elementary encryption mode like ECB and CBC modes is potential for a practical use. However, at SAC 2009, Gennaro and Halevi showed that a key wrapping scheme using a universal hash function and ECB mode (a HtECB scheme) is broken, and the security of a scheme based on a universal hash function and CBC mode (a HtCBC scheme) has been left as an open problem. In this paper, we first generalize classical notions of universal and uniform hash functions, and propose a total of four new notions of the keyed hash function. We then prove that HtECB and HtCBC schemes are secure key wrapping schemes if the universal hash function satisfies uniformity and our notions, where the result on the HtCBC scheme gives a partial answer to the open problem. Then we discuss a basic problem of identifying relations between various notions of a keyed hash function, and point out that a monic polynomial hash function satisfies all the new notions.

Osaki Y, Morita Y, Kuwahara T, Miyano I, Doi Y. Prevalence of Parkinson’s disease and atypical parkinsonian syndromes in a rural Japanese district. Acta Neurol Scand: 2011: 124: 182–187. © 2010 John Wiley & Sons A/S. Objectives – To investigate the prevalence of Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS) in a rural Japanese district. Method – Collaboration with the medical institutions, the long-term care insurance system facilities, and the public health office. Results – The crude prevalence rates were 175 per 100 000 (95% CI: 143–206) for PD, 18 (8–28) for progressive supranuclear palsy, 17 (7–26) for multiple system atrophy (MSA), and 9 (2–16) for corticobasal degeneration. The age-adjusted prevalence rates were 109 per 100 000 (88–134), 10 (2–17), 13 (4–21), and 6 (0–12), for each condition. There was a preponderance of women with PD and of men with APS. Nine of the 116 PD patients and 7 of the 29 APS patients were newly diagnosed in this study. Conclusions – There are high prevalence rates for PD and APS and suboptimal recognition of APS. This is the first epidemiological prevalence study of MSA from Japan.

Although dementia is increasingly recognized as a common feature in Parkinson's disease (PD), its pathological substrate remains unknown. We conducted cross-sectional and longitudinal brain perfusion SPECT analyses to explore changes during the course of developing dementia in PD. Fifty-five patients originally diagnosed with PD were imaged in the cross-sectional study. Twenty-one of these, nine without dementia and 12 with dementia (PDD), were included in the longitudinal study to observe perfusion changes during the course of their disease. Data were analyzed using three-dimensional stereotactic surface projection SPECT analysis. The UK Parkinson's Disease Society Brain Bank criteria were used to diagnose PD and the revised criteria for the clinical diagnosis of dementia with Lewy bodies for PDD. The cross-sectional study showed that patients with PDD had significantly reduced perfusion in the right posterior cingulate, the right precuneus and the left posterior cingulate area. In the longitudinal study, significantly reduced perfusion was observed in the left anterior frontal gyrus in PD without dementia, and in the right inferior parietal lobule in those that developed PDD. We suggest that a relationship exists between developing dementia in PDD and reduced perfusion in the posterior parietal area.

Aim: To identify factors associated with falling, we assessed the Tinetti Gait and Balance Scale (TGBS) for patients with Parkinson’s disease (PD) and atypical parkinsonism (AP), and assessed the Unified Parkinson’s Disease Rating Scale (UPDRS) for patients with PD. Methods: A cross sectional study was conducted in a university hospital, with the subject constituting 30 PD patients and 22 AP patients. Each item included in the TGBS and the UPDRS part III were scored in the clinical setting. Fallers were categorized if the patient experienced at least one fall in the prior six-month period. Results: Thirty-five patients were categorized as fallers. When comparing PD fallers and PD non-fallers, a subscore comprising a sum with ‘walk stance’ and ‘nudge on sternum’ in the TGBS showed a significant difference. Total UPDRS part III score indicated a significant difference during the medication ON period, whereas the difference was insignificant during the medication OFF period. The presence of dyskinesia or freezing of gait was not different. In addition, ‘walk stance’ only in the TGBS showed a significant difference between PD fallers and AP fallers. Conclusions: We concluded that ‘walk stance’ and ‘nudge on sternum’ in the TGBS may be useful for evaluating factors associated to falling in PD. ‘Walk stance’ item merits inclusion into routine assessment in PD in addition to UPDRS part III.

Background: Age-associated cognitive decline (AACD) is a predictor of dementia and highly prevalent among elderly people. Many elderly people with AACD also suffer from depressive moods. We studied, the effect of group work programs on the cognitive function and quality of life (QOL) of community-dwelling elderly people with AACD and/or mild depressive moods. Methods: Thirty-six subjects, with a mean age of 79.8 years, were included in this study. Twenty-one suffered from both AACD and mild depressive moods, nine suffered from mild depressive moods and six from AACD. Subjects were required to participate in a number of group work programs, such as music therapy, handicrafts and so on. They were assigned to one of two groups, and each participated in two 4-month sessions. In the first session, group 1 participated in the group work programs, while group 2 did not (control). In the second session, group 2 participated while group 1 did not. The effect of group work on elderly people with AACD (n = 27) and depressive moods (n = 31), was evaluated separately. Results: Improvement was observed in depressive moods and QOL (visual analogue scale of family relation, friendship and happiness, life satisfaction index) in subjects with cognitive impairment and depressive moods. The effect on cognitive function was shown only in elderly individuals suffering from depressive moods. The improvement in depressive moods and QOL seemed to be accompanied by an improvement in cognitive function but did not continue after completion of the group work program. Conclusion: Group work was shown to improve depressive moods, QOL and cognitive function; however, long-term effects require further examination.

We investigated regional cerebral blood flow (rCBF) using three-dimensional stereotactic surface projection (3D-SSP) analysis in 30 patients initially diagnosed as Parkinson's disease (PD), and compared differences in rCBF between patients with and without PD-related manifestations. 3D-SSP analysis of cerebral perfusion was performed by use of a control database. Compared to age-matched controls, there were multiple hypoperfusion areas in cases where the original diagnosis was PD. Temporal bases showed the lowest perfusion; frontal bases and medial parietal lobes the second; visual cortices the third; and parietal association areas exhibited the fourth lowest. During the clinical course, 10 of the patients suffered dementia, 9 had fluctuating cognition, and 19 experienced repeated visual hallucinations. Significant negative correlations were observed between dementia and the bilateral posterior cingulate area, and among fluctuating cognition and bilateral medial parietal lobes, parietal association areas, and dorsal occipital lobes. Repeated visual hallucinations did not show any correlation with any region of interest. We concluded that multiple hypoperfusion areas were observed in the 3D-SSP SPECT analysis. Although the presence of dementia showed a significant relationship with the bilateral posterior cingulate areas, perfusion in the frontal bases, temporal bases, or parietal lobes was markedly more reduced than that seen in the bilateral posterior cingulate areas.

We assessed the accuracy of clinical diagnosis of progressive supranuclear palsy (PSP, Steele-Richardson-Olszewski disease) and the validity of existing sets of clinical diagnostic criteria for PSP (see Appendix) using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Diagnosis of PSP was made by 40 different physicians, and 60 cases clinically diagnosed as PSP when last assessed in life were studied. In 47 cases (78%), the diagnosis of PSP was confirmed pathologically. False-positive diagnoses included Parkinson's disease with significant additional cortical Lewy body (n = 3) or Alzheimer (n = 1) pathology, multiple system atrophy (n = 4), and corticobasal degeneration, Pick's disease, motor neurone disease, cerebrovascular disease, and a sporadic case of frontotemporal dementia and parkinsonism linked to chromosome 17 (1 case each). Most cases of PSP were diagnosed accurately by neurologists at the final assessment. Although application of National Institute of Neurological Disorders and the Society for PSP possible category marginally improved the accuracy of initial clinical diagnosis, none of the existing operational criteria could significantly improve accuracy of the final clinical diagnosis.

It has been reported that up to 80% of patients clinically diagnosed as having progressive supranuclear palsy (PSP) may have arterial hypertension (HT). Because previous studies were performed on patients with presumed diagnosis of PSP, we tried to replicate these studies in a series of pathologically confirmed patients. Seventy-three patients with a neuropathological diagnosis of PSP autopsied at the Queen Square Brain Bank for Neurological Disorders in London were collected between 1989 and 1999. For the purpose of this study, patients were considered hypertensive if a blood pressure above 140/90 mm Hg was found in the clinical records. The prevalence of HT in PSP patients at the first and at the last visit during their neurological disease was compared with that found in a series of 21 normal controls who donated their brain to the same institution. Overall, 29 of 73 (39.7%) of the patients were recorded as having HT at the first visit during the disease course; this ratio increased to 42 of 73 (57.5%) at the last visit before death. When these figures were compared to the 21 normal controls (11 of 21 with HT, 52.4%), we were unable to find an increased prevalence of HT in PSP (odds ratio, 0.60; 95% confidence interval, 0.20-1.76). Therefore, HT does not represent an important clinical feature of this neurodegenerative disorder, although cerebrovascular disease can masquerade clinically as PSP.

Background: The aim of the present paper was to assess the prevalence of atherosclerotic aortic plaques in non-rheumatic atrial fibrillation and their relation to ischemic stroke. Although aortic plaques are frequently seen in the elderly, their significance remains unclear in relation to ischemic stroke in patients with atrial fibrillation. Methods: Transesophageal echocardiography was performed on 56 patients (age 61 ± 10 years) with atrial fibrillation. The aorta was divided into two segments (i.e. the proximal aorta that includes the ascending aorta and the aortic arch proximal to the ostium of the left subclavian artery, and the distal aorta that is the descending aorta distal to the left subclavian artery). Thickened intima = 3 mm in thickness was defined as aortic plaques. Results: Ischemic stroke was found in 14 of the 56 patients. Aortic plaques were detected in 25 of the 56 patients. All of these 25 patients had aortic plaques in the proximal aorta, and 17 of them also had aortic plaques in the distal aorta. Ischemic stroke was found in 11 of the 25 patients (44%) with aortic plaques, and three of the 31 patients (10%) without aortic plaques (P < 0.01). Conversely, aortic plaques were detected in 11 of the 14 patients (79%) with ischemic stroke, and in 14 of the 42 patients (33%) without (P < 0.01). The patients with ischemic stroke had a larger left atrium (47 ± 5 vs 43 ± 6 mm; P < 0.05) than those without. Aortic plaques were a correlate only of previous ischemic stroke (P < 0.05) by multiple logistic regression analysis. Conclusions: Atherosclerotic aortic plaques detected by transesophageal echocardio-graphy are a correlate of previous ischemic stroke in patients with non-rheumatic atrial fibrillation.

BACKGROUND: Several studies in older people have found a U-shaped or J-shaped association of blood pressure with mortality. The increased mortality associated with the lowest levels of blood pressure in older people have been explained by concurrent illnesses and frailty, but previous studies used blood pressure measured on a single occasion. Such a casual value is different from the long-term average of blood pressure. We investigated the relation between the average level of 5-day consecutive home blood pressure and mortality in older people while adjusting for potential confounding factors including morbidity and frailty at baseline. METHODS: In 1992, 1186 community residents of a rural Japanese town, Kahoku, aged 65 or older, measured their blood pressure in their homes 20 times (four times per day, 5 consecutive days). The mean value of the 20 measurements was used to examine the association between home BP and subsequent 4-year mortality. A proportional hazards model was fitted while adjusting for activities of daily living impairment, medical history, antihypertensive medication, smoking, use of alcohol, and depression. RESULTS: A total of 134 persons died during the four-year follow-up period. There was no significant evidence that frailty is more prevalent in the lowest or highest systolic BP group than in intermediate groups. A U-shaped association between the average level of home systolic blood pressure and mortality was found in men while adjusting for potential confounding factors, including morbidity and frailty. We also showed the U-shaped curve of the association of systolic BP with all cause and noncardiovascular mortality in the whole population and the linear association of systolic BP with cardiovascular mortality. CONCLUSIONS: We showed a U-shaped association between the average level of systolic blood pressure measured at home and mortality in older men while adjusting for potential confounding factors including morbidity and frailty. Not only high home systolic BP, but also low home systolic BP, is an independent risk factor for mortality in older men. The mechanisms underlying the association between BP and mortality differ by levels of systolic BP. Cardiovascular deaths tended to be higher in the highest SBP group, and only noncardiovascular deaths were increased in the lowest SBP group. The latter finding suggests that low SBP may be not only an independent risk of mortality but also an indicator of a subclinical noncardiovascular comorbid condition. J Am Geriatr Soc 47:1415–1421, 1999.

We describe a 48-year-old female with an isolated unilateral hypoglossal nerve palsy caused by a skull base metastasis from breast cancer. The patient had a medical history of conservative breast therapy for breast cancer. Although the cause of such a neurological deficit includes various pathologies, the reports focusing on metastatic tumor have been limited in number. Radiologic investigation showed a mass involving both the right hypoglossal canal and the clival edge. Swelling of the hypoglossal nerve was observed in views including its canal. Three-dimensional CT images demonstrated the tumor protruding from the enlarged external orifice of the hypoglossal canal. In the present report we mentioned a nuclear medicine procedure to visualize and characterize the small, abnormal tissue in the skull base. Dual-isotope SPECT confirmed an abnormal uptake of 99mTc-HMDP around the hypoglossal canal and a 201Tl-positive elongated lesion running along the hypoglossal nerve.

A comparative study is reported in which kaolinite has been hydrothermally synthesized at several pH conditions. The syntheses were carried out at 220 °C for 3 to 10 d with distilled water or acidic solutions using a mixture of silica-gel derived from alkoxide and gibbsite with a Si/Al ratio of 1 :1 as the starting material. Use of acidic solution for the synthesis promotes the dissolution of the starting materials and leads to kaolinitization at an earlier stage of the reaction. However, the rate of kaolinitization is found to be rather slow, in comparison to the reaction with distilled water. The synthetic kaolinite was characterized by X-ray powder diffraction pattern. Kaolinite synthesized with distilled water was poorly grown for direction of the stacking. For example, crystallite size along the c*-axis = 155 A, whereas kaolinite synthesized with acidic solution gave a higher crystallite size along the c*-axis, such as 253 A in the case of the synthesis with 0.1 N HCI. Hinckley index of the synthetic kaolinite was varied from 0.35 to 0.80 by the acidity of the reaction. Different kaolinitization processes are implied by differences observed in the rate of kaolinitization, which has an influence on the nature of the stacking faults of the kaolinite.

脳梗塞急性期における昇圧ならびに降圧の減少が一種の代償性機構であるとの仮説のもとに, 脳梗塞急性期の血圧の推移と神経学的重症度との関連を検討した.対象は急性期脳梗塞患者65例 (男 : 女=33 : 32, 平均年齢68。5±12.2歳) で, 各々につき神経学的重症度の評価, 随時血圧及び24時間血圧の測定と, 血小板凝集能及び交感神経機能の指標としてβ-TGの測定を行った.脳梗塞急性期において, 夜間降圧度の減少と神経学的重症度との間には有意の相関があり, また日単位の降圧度と神経学的重症度の間にも有意の相関が認められた.以上の事実より, 脳梗塞急性期の昇圧ならびに降圧の減少は交感神経系の興奮を介した代償性機序である可能性が示唆された.

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Changes in finger positions influence the waveform of CMAP recorded from the muscle that moves that finger. The present study suggested that the muscle length, dependent on the finger position, was a main factor affecting the waveform. On shortening the muscle length, the amplitude of CMAP increased with concomitant reduction in the duration, and on lengthening, the amplitude decreased with concomitant increase in the duration. These changes are considered due to changes in propagation velocities of muscle fibers dependent on the muscle length. In nerve conduction studies, it is important to carefully monitor the finger position to distinguish the waveform changes with muscle length from those due to nerve lesions.

Kaolinite was hydrothermally synthesized from two kinds of silica-alumina gels to examine the effect of the structure of the starting material. Two kinds of gels were prepared by precipitation at different pH conditions (pH = 9.6 and 4.2) from solutions containing water glass and aluminum sulfate. Na ions in the gels were removed with a resin before the hydrothermal treatment, but a slight amount of sulfate ions was still present in the gels. The nuclear magnetic resonance spectra of the starting gels suggested that the gel prepared at pH 9.6 consists of networks with alternating SiO4- and A104-tetrahedra (partially A106-octahedra), whereas the gel prepared at pH 4.2 consists of a sheet structure related to allophane. After the hydrothermal treatment at 220"C for 9 days, kaolinite particles with spherical shape were obtained from the former gel, and platy kaolinite was crystallized from the latter one. The difference in morphology of synthetic kaolinite was attributable to the structures of the starting gels, and the pH values in the hydrothermal reactions were not very significant to the morphology.

Key wrapping schemes are used to encrypt data of high entropy, such as cryptographic keys. There are two known security definitions for key wrapping schemes. One captures the security against chosen plaintext attacks (called DAE-security), and the other captures known plaintext attacks (called AKW-security). In this paper, we revisit the security of Hash-then-CBC key wrapping schemes. At SKEW 2011, Osaki and Iwata showed that the U CC -then-CBC key wrapping scheme, a key wrapping scheme that uses the U CC hash function and the CBC mode, has provable AKW-security. In this paper, we show that the scheme achieves the stronger notion of DAE-security. We also show our proof in the variable input length setting, where the adversary is allowed making queries of varying lengths. To handle such a setting, we generalize the previous definition of the U CC hash function to the variable input length setting, and show an efficient construction that meets the definition. We next consider linear-then-CBC, 2nd-preimage-resistant-then-CBC, and universal-then-CBC schemes. At SAC 2009, Gennaro and Halevi noted that these schemes do not achieve DAE-security. However, details were not presented, and we show concrete and efficient chosen plaintext attacks on these schemes, and confirm that they do not achieve DAE-security.

The revised (new) consensus clinical diagnostic criteria for multiple system atrophy (MSA) were published in 2008. To validate these criteria, we utilized the same cohort that we reported previously, which included 59 patients with a clinical diagnosis of MSA that was confirmed neuropathologically in 51 of them at the Queen Square Brain Bank for Neurological Disorders. At the first clinic visit, sensitivity with new consensus possible category was higher, and PPV marginally higher, than for clinical diagnosis and old consensus possible category. New consensus probable category showed marginally higher sensitivity than, and the same PPV as, old consensus probable category. At the last clinic visit, new consensus possible category had exactly the same sensitivity and only marginally higher PPV compared with old consensus possible category. New consensus probable category showed the same sensitivity and PPV as old consensus probable category. Our data indicate that in this case material the new consensus criteria for possible MSA could improve diagnostic accuracy at first neurological evaluation compared with the old consensus criteria. Prospective clinicopathological validation studies of the new consensus criteria, particularly incorporating in vivo structural and functional imaging results, are required to extend the current findings.

Objective: To assess the accuracy of a clinical diagnosis of multiple system atrophy (MSA) and compare it to the Quinn and Consensus criteria for MSA using neuropathologically examined cases from the Queen Square Brain Bank for Neurological Disorders. Methods: Fifty-nine cases with a neurologic diagnosis of MSA when last assessed prior to death were studied. Results: In 51 (86%) of these cases, the diagnosis of MSA was confirmed pathologically. False positive diagnoses included PD (n = 6), progressive supranuclear palsy (n = 1), and cerebrovascular disease (n = 1). When applying either set of diagnostic criteria, a diagnosis of probable MSA gave lower sensitivity but higher positive predictive value than one of possible MSA. Application of either set of diagnostic criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by the last clinic visit. Conclusions: This study shows a high diagnostic accuracy for the clinical diagnosis of MSA by neurologists, with PD accounting for most of the false positive diagnoses. Application of either Quinn or Consensus criteria was superior to actual clinical diagnosis made early in the disease, but there was little difference by last clinic visit.

AIMS To evaluate whether thoracic aortic plaques together with dyslipidaemia are related to ischaemic stroke, and if so, to which of the subtypes of stroke. METHODS AND RESULTS We performed transoesophageal echocardiography in 50 patients with acute ischaemic stroke and in 401 controls. The aorta was divided into two segments: (1) the proximal, proximal to the left subclavian artery, and (2) the distal aorta. Protruding plaques (Intima > or =4 mm in thickness) in the proximal aorta were detected in 14 of the 50 patients (28%) with stroke, and in 53 of the 401 controls (13%) (P

To examine the clinical implications of post-stroke hypertension, defined as the rise in blood pressure on admission after the onset of ischemic stroke as compared with the blood pressure before stroke, and to assess the relationship between the value of post-stroke hypertension and neurologic recovery, we retrospectively studied 28 patients admitted to the hospital within 24h (mean±SD, 6.7±7.0h) after a firstever, acute non-embolic ischemic stroke, whose blood pressure had been recorded at the outpatient clinic within 3 mo before stroke. The Canadian Neurological Scale was used to assess stroke severity, and neurologic recovery during the acute phase was calculated. The average duration of hospitalization was 18±9d. The value of post-stroke hypertension and stroke severity on admission independently and significantly correlated with neurologic recovery (odds ratio, 1.06; 95% confidence interval, 1.00-1.12 and odd ratio, 0.20; 95% confidence interval, 0.06-0.72, respectively). There was also a significant linear correlation between the value of post-stroke hypertension and neurologic recovery (r= 0.50, p

We report a man who developed selenium-deficient myopathy during long-term parenteral nutrition. Muscle biopsy showed marked mitochondrial depletion in the deep sarcoplasm and enlarged mitochondria at the periphery mainly in type 2 fibers. Muscle weakness improved gradually after the second course of selenium supplementation. The peculiar mitochondrial abnormalities in muscle fibers appear to play a key role in the pathogenesis of selenium-deficient myopathy.

Background and Purpose Postural hypotension, which occurs frequently in community-living, apparently healthy elderly adults, is usually asymptomatic. However, the relation between postural changes in blood pressure and quantitative higher cerebral function or silent brain lesions remains unclear. We examined the association of exaggerated postural changes in systolic blood pressure with cognitive and quantitative neurobehavioral functions and with brain lesions on MRI in the community-dwelling older elderly. Methods The study population consisted of 334 community-dwelling elderly adults, aged 75 years or older (mean age, 80 years). Postural changes in systolic blood pressure (SBP) were assessed using an autosphygmomanometer (BP-203 I). By the difference between the mean of two measurements of SBP at standing and at supine position (dSBP=SBP at upright−SBP at supine position), we divided the subjects into three groups: (1) 20 subjects with postural hypotension (d-SBP ≦−20 mm Hg), (2) 29 subjects with postural hypertension (dSBP ≧20 mm Hg), and (3) 285 subjects with postural normotension (20 Results Twenty subjects (6.0%) exhibited postural hypotension and 29 (8.7%) postural hypertension. Scores in neurobehavioral functions and activities of daily living were significantly lower in the postural dysregulation group (both postural hypotension and hypertension groups) than in the postural normotension group. The postural dysregulation group exhibited significantly more advanced periventricular hyperintensities than the normotension group. Conclusions Asymptomatic community-dwelling elderly individuals with postural hypotension as well as those with postural hypertension had poorer scores on neurobehavioral function tests and more advanced leukoaraiosis demonstrated on MRI than those without exaggerated postural changes in SBP.

Osaki Y, Koga M, Matsubayashi K, Yuki N. Asymmetric pharyngeal–cervical–brachial weakness associated with anti-GT1a IgG antibody. Acta Neurol Scand 2002: 106: 234–235. © Blackwell Munksgaard 2002. We report a case of markedly asymmetric pharyngeal–cervical–brachial weakness. Acute progression of symptoms, albuminocytologic dissociation in cerebrospinal fluid, electrophysiologic evidence of demyelination and elevation of IgG anti-GT1a antibody titer paralleled the clinical course, support the diagnosis of Guillain–Barre syndrome. Guillain–Barre syndrome should be considered in the differential diagnosis of cranial neuropathy, even in cases where there is marked asymmetry.

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Vol 350 • November 22, 1997 1521 reported to be expressed specifically in the brain based on northern studies, our ability to detect necdin transcripts in the liver suggests a lower, but detectable level of expression in peripheral tissues. We further examined necdin imprinting by testing expression by RT-PCR with RNA from cultured fibroblasts derived from a normal control and three patients with PWS and three with Angelman syndrome (AS), each with a documented 15q11-q13 deletion (figure B). This analysis likewise revealed imprinted expression, with necdin mRNA detectable in normal and AS samples, but not in PWS samples. The overall level of expression in cultured fibroblast cells may be quite low, given a less robust PCR product than that seen in the liver. These results show that necdin is imprinted with paternal-specific transcription in multiple tissues, including brain, which is the predominant site of its expression, and are consistent with another report indicating imprinted expression of necdin in newborn mouse brain and human fibroblasts. Necdin was initially identified as a mRNA specific to postmitotic, differentiated neuron from embryonal carcinoma cells, and found in the mouse to be expressed only in the central nervous system by northern analysis. In mouse development, necdin is expressed abundantly during periods of neural generation and differentiation, and expression is detected throughout the brain of the adult mouse, with the highest expression in the hypothalamus and midbrain. This Imprinting analysis of the human necdin gene RT-PCR on RNA from brain and liver controls and a PWS patient with a 15q11-q13 deletion (A), and RNA from cultured fibroblast cell lines from a control, three deletion PWS patients and three deletion AS patients (B). Expression of a second gene not on chromosome 15 (LDL receptor) was used as a control for RNA quality, and –RT controls are shown for necdin, whose product is colinear with genomic DNA. Details of RNA preparation and RT-PCR can be obtained from the author. Quality of life of old people living in the community