Genetic characterization of measles virus genotype D6 subacute sclerosing panencephalitis case, Alberta, Canada.

Subacute sclerosing panencephalitis (SSPE) is a progressive and eventually fatal neurological disease arising from a persistent infection with measles virus (MV) acquired at a young age. SSPE measles virus strains are defective and unable to produce progeny virions, due to multiple and extensive mutations in a number of key genes. We sequenced the full MV genome from our recently reported SSPE case, which typed as genotype D6, and compared it with other genotype D6 wild type and SSPE sequences. The Alberta D6 strain was significantly different from other reported SSPE D6 sequences. Mutations were observed in all the genes of the Alberta strain, with the greatest sequence divergence noted in the M gene with 17.6% nucleotide and 31% amino acid variation. The L gene showed the least variation with 1.3% nucleotide and 0.7% amino acid differences respectively. The nucleotide variability for 15,672 bases of the complete genome compared to the wild type and other SSPE D6 strains was around 3%.

Global transcriptome profiling of mild relapsing-remitting versus primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Genetic research in multiple sclerosis (MS) mostly compares patients with MS with healthy controls, but does not differentiate between MS disease courses. We compared peripheral blood gene expression patterns between extremes of MS phenotypes, i.e. patients with mild relapsing-remitting MS (mRRMS) and primary progressive MS (PPMS). METHODS: We analyzed global gene expression profiles of peripheral blood samples of age- and gender-matched patients with mRRMS and PPMS. Detailed bioinformatic and gene set enrichment analysis, pathway and principle component analyses were used to identify differentially expressed genes and pathways. RESULTS: A total of 84 genes were significantly deregulated between the groups. Of those, 19 had been previously reported to be deregulated in patients with MS as compared with healthy controls, including major histocompatibility complex, interferon receptor 2 and interleukin 6 receptor. Detailed molecular pathway analysis revealed significant up-regulation of antigen processing and presentation, leukocyte transendothelial migration, nucleotide-binding oligomerization domain-like receptor signaling, chemokine signaling and down-regulation of RNA transport, spliceosome and aminoacyl-tRNA biosynthesis pathways in PPMS compared with mRRMS. CONCLUSION: Our analyses show significant differences between mRRMS and PPMS gene expression. Surprisingly, the differentially expressed genes were mostly involved in immunological and inflammatory pathways, suggesting that the difference in MS phenotypes is caused primarily by a difference in immune responses. It should be kept in mind that our analyses were in peripheral blood only, and that the observed differences in inflammatory pathways may be a substrate of the analysed tissue. Further research into gene expression differences between disease courses including analyses in central nervous system tissue is warranted.

Smoking does not influence disability accumulation in primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: The modifiable risk factor cigarette smoking has been associated with an increased risk of developing multiple sclerosis (MS) and with disease activity in relapsing-remitting MS. However, less is known about the effect of smoking on disease progression in progressive MS. Here the association between cigarette smoking and disability accumulation in primary progressive MS (PPMS) is investigated. METHODS: Kaplan-Meier survival analyses and Cox proportional hazard modelling were used to investigate the influence of cigarette smoking on the risk of reaching Expanded Disability Status Scale (EDSS) 4 and 6 as well as the time from EDSS 4 to 6 in patients with PPMS. RESULTS: In all, 416 patients with PPMS and available smoking history were identified. Median time to EDSS 4 was 4 years in ever-smokers and 5 years in never-smokers (P = 0.27), and it was 9 years to EDSS 6 in both ever-smokers and never-smokers (P = 0.48). Smokers were not at increased risk of faster progression to EDSS 4, 6 and from EDSS 4 to 6. Age at disease onset was the strongest risk factor for progression to EDSS 4, 6 and from EDSS 4 to 6. CONCLUSIONS: Our investigation of a large and well-characterized population based PPMS cohort suggests that cigarette smoking does not influence disability accumulation in PPMS. Our findings support the idea that PPMS is driven by different underlying pathomechanisms than relapsing-remitting MS.

MS incidence and prevalence in Africa, Asia, Australia and New Zealand: A systematic review.

OBJECTIVES: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality. METHODS: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate. RESULTS: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia. CONCLUSIONS: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study.

Performance on Paced Auditory Serial Addition Test and cerebral blood flow in multiple sclerosis.

BACKGROUND: To assess the relationship between performance on the Paced Auditory Serial Addition Test (PASAT) and both cerebral blood flow (CBF) and axonal metabolic integrity in normal appearing white matter (NAWM) of the centrum semiovale in patients with multiple sclerosis (MS). METHODS: Normal appearing white matter of the centrum semiovale was investigated with magnetic resonance (MR) imaging in 28 non-depressed individuals (18 patients with MS and 10 healthy controls). CBF was assessed with pseudo-continuous arterial spin labeling. N-acetylacetate/creatine (NAA/Cr) ratios (a metabolic axonal marker) were measured using (1) H-MR spectroscopy. CBF was also measured in frontoparietal cortices and cerebellar hemispheres. RESULTS: In subjects with MS, we found a positive correlation between performance on the PASAT and CBF to the left centrum semiovale (P = 0.008), but not with the NAA/Cr ratio. There were no correlations between PASAT scores and CBF to the right centrum semiovale, frontoparietal cortices, and cerebellar hemispheres. There was no correlation between PASAT scores and NAA/Cr ratios. CONCLUSIONS: Our preliminary results suggest that performance on the PASAT in subjects with MS correlates with CBF to the left centrum semiovale, which contains left frontoparietal white matter association tracts involved in information processing speed and working memory.

T2 lesions and rate of progression of disability in multiple sclerosis.

BACKGROUND AND PURPOSE: To assess the predictive value of T2 lesions on the rate of progression of disability in multiple sclerosis (MS). METHODS: We reanalyzed T2 lesion number and load on brain MRI scans, performed before 1997, of 186 MS patients, who were clinically followed. There were 90 patients with progressive MS (35 secondary progressive and 55 primary progressive), and 96 with relapsing remitting MS. The rate of progression of disability was measured by time to sustained progression of disability (defined as an increase in ≥ 1 point when the Expanded Disability Status Scale (EDSS) was 5.5 or less and an increase in EDSS of ≥ 0.5 point when the EDSS was 6.0 or higher), and by the Multiple Sclerosis Severity Score (MSSS). RESULTS: During follow-up (median 15 years, IQR 12-17 years), 94% of the patients with progressive MS and 50% of the patients with relapsing remitting MS had progression of disability. Higher T2 lesion number and load were modestly associated with a higher rate of disease progression on the MSSS and a shorter time to progression of disability in relapsing remitting MS, but not in progressive MS. CONCLUSIONS: Our findings indicate that the amount of T2 lesions has a small predictive value for progression of disability in relapsing remitting MS, but has no influence on the rate of progression in progressive MS.

Does smoking influence outcome after intravenous thrombolysis for acute ischaemic stroke?

BACKGROUND AND PURPOSE: It remains uncertain whether current smoking influences outcome in patients with acute ischaemic stroke. OBJECTIVES: To evaluate the effect of current smoking in routinely tissue plasminogen activator (tPA)-treated stroke patients on the 3-month functional outcome and the occurrence of symptomatic intracerebral hemorrhage (ICH). METHODS: We analyzed data from a single stroke care unit registry of 345 consecutive patients with ischaemic stroke, treated with tPA. Logistic regression models were used to assess if smoking was independently associated with 3-months good outcome defined as a modified Rankin Scale score of < or =2, and the occurrence of symptomatic ICH. RESULTS: In the multivariable models, smoking was not associated with a good outcome or a decreased risk of symptomatic ICH. CONCLUSION: Current smoking did not affect functional outcome at 3 months or the risk of symptomatic ICH in patients routinely treated with tPA for ischaemic stroke.

Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients.

N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with (1)H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies.

Lipid profile, statin use, and outcome after intravenous thrombolysis for acute ischaemic stroke.

BACKGROUND: Low cholesterol levels have been associated with an increased risk of haemorrhagic stroke. This study investigated whether lipid levels or prior statin use influence outcome in patients with acute ischaemic stroke treated with IV thrombolysis. METHODS: The relation between admission lipid levels or statin use and both the development of symptomatic intracerebral haemorrhage (sICH) and 3-months functional outcome was assessed in a prospective hospital-based stroke registry comprising 252 patients treated with IV tissue plasminogen activator (tPA). The fasting status of the patients was unknown. Favourable outcome at 3 months was defined as a modified Rankin scale score

Relationship between the extent of T2 lesions and the onset of secondary progression in multiple sclerosis.

Patients with relapsing-remitting multiple sclerosis (MS) are at risk of converting to a secondary progressive disease course. To assess the relationship between brain magnetic resonance imaging (MRI) findings and onset of secondary progression, we reanalyzed the initial brain MRI scans of 90 relapsing-remitting MS patients, who were clinically followed up for at least 10 years (median 14 years) after their scan, for the number and volume of T2 lesions, and for two measures of brain atrophy (bicaudate ratio and third ventricle width). The relationship to development of secondary progression was studied with Cox regression models and Kaplan-Meier survival analyses. At the end of follow-up, 36 patients had become progressive. The presence of more than 10 T2 lesions more than doubled the risk of becoming secondary progressive (hazards ratio 2.36; 95% CI 1.19-4.66). When at least one of the 10 lesions was confluent the risk increased to 3.51 (1.64-7.50). The hazards ratio for an estimated T2 lesion load of more than 800 mm(3) was 2.11 (1.07-4.16). Linear brain atrophy measures were not predictive. Our data show a relationship between the extent of brain T2 lesions and the onset of secondary progression in MS.

Acculturation and mental health--empirical verification of J.W. Berry's model of acculturative stress.

OBJECTIVES: Many studies concerning mental health among ethnic minorities have used the concept of acculturation as a model of explanation, in particular J.W. Berry's model of acculturative stress. But Berry's theory has only been empirically verified few times. The aims of the study were to examine whether Berry's hypothesis about the connection between acculturation and mental health can be empirically verified for Greenlanders living in Denmark and to analyse whether acculturation plays a significant role for mental health among Greenlanders living in Denmark. STUDY DESIGN AND METHODS: The study used data from the 1999 Health Profile for Greenlanders in Denmark. As measure of mental health we applied the General Health Questionnaire (GHQ-12). Acculturation was assessed from answers to questions about how the respondents value the fact that children maintain their traditional cultural identity as Greenlander and how well the respondents speak Greenlandic and Danish. The statistical methods included binary logistic regression. RESULTS: We found no connection between Berry's definition of acculturation and mental health among Greenlanders in Denmark. On the other hand, our findings showed a significant relation between mental health and gender, age, marital position, occupation and long-term illness. CONCLUSION: The findings indicate that acculturation in the way Berry defines it plays a lesser role for mental health among Greenlanders in Denmark than socio-demographic and socio-economic factors. Therefore we cannot empirically verify Berry's hypothesis.

Using polygons to recognize and locate partially occluded objects.

We present computer vision algorithms that recognize and locate partially occluded objects. The scene may contain unknown objects that may touch or overlap giving rise to partial occlusion. The algorithms revolve around a generate-test paradigm. The paradigm iteratively generates and tests hypotheses for compatibility with the scene until it identifies all the scene objects. Polygon representations of the object's boundary guide the hypothesis generation scheme. Choosing the polygon representation turns out to have powerful consequences in all phases of hypothesis generation and verification. Special vertices of the polygon called ``corners'' help detect and locate the model in the scene. Polygon moment calculations lead to estimates of the dissimilarity between scene and model corners, and determine the model corner location in the scene. An association graph represents the matches and compatibility constraints. Extraction of the largest set of mutually compatible matches from the association graph forms a model hypothesis. Using a coordinate transform that maps the model onto the scene, the hypothesis gives the proposed model's location and orientation. Hypothesis verification requires checking for region consistency. The union of two polygons and other polygon operations combine to measure the consistency of the hypothesis with the scene. Experimental results give examples of all phases of recognizing and locating the objects.