Anatomy and Neuroscience - Research Publications
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ItemOptic Nerve Magnetisation Transfer Ratio after Acute Optic Neuritis Predicts Axonal and Visual OutcomesWang, Y ; van der Walt, A ; Paine, M ; Klistorner, A ; Butzkueven, H ; Egan, GF ; Kilpatrick, TJ ; Kolbe, SC ; Villoslada, P (PUBLIC LIBRARY SCIENCE, 2012-12-18)Magnetisation transfer ratio (MTR) can reveal the degree of proton exchange between free water and macromolecules and was suggested to be pathological informative. We aimed to investigate changes in optic nerve MTR over 12 months following acute optic neuritis (ON) and to determine whether MTR measurements can predict clinical and paraclinical outcomes at 6 and 12 months. Thirty-seven patients with acute ON were studied within 2 weeks of presentation and at 1, 3, 6 and 12 months. Assessments included optic nerve MTR, retinal nerve fibre layer (RNFL) thickness, multifocal visual evoked potential (mfVEP) amplitude and latency and high (100%) and low (2.5%) contrast letter acuity. Eleven healthy controls were scanned twice four weeks apart for comparison with patients. Patient unaffected optic nerve MTR did not significantly differ from controls at any time-point. Compared to the unaffected nerve, affected optic nerve MTR was significantly reduced at 3 months (mean percentage interocular difference = -9.24%, p = 0.01), 6 months (mean = -12.48%, p<0.0001) and 12 months (mean = -7.61%, p = 0.003). Greater reduction in MTR at 3 months in patients was associated with subsequent loss of high contrast letter acuity at 6 (ρ = 0.60, p = 0.0003) and 12 (ρ = 0.44, p = 0.009) months, low contrast letter acuity at 6 (ρ = 0.35, p = 0.047) months, and RNFL thinning at 12 (ρ = 0.35, p = 0.044) months. Stratification of individual patient MTR time courses based on flux over 12 months (stable, putative remyelination and putative degeneration) predicted RNFL thinning at 12 months (F(2,32) = 3.59, p = 0.02). In conclusion, these findings indicate that MTR flux after acute ON is predictive of axonal degeneration and visual disability outcomes.
ItemClosing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjectsLill, CM ; Liu, T ; Schjeide, B-MM ; Roehr, JT ; Akkad, DA ; Damotte, V ; Alcina, A ; Ortiz, MA ; Arroyo, R ; Lopez de lapuente, A ; Blaschke, P ; Winkelmann, A ; Gerdes, L-A ; Luessi, F ; Fernadez, O ; Izquierdo, G ; Antigueedad, A ; Hoffjan, S ; Cournu-Rebeix, I ; Gromoeller, S ; Faber, H ; Liebsch, M ; Meissner, E ; Chanvillard, C ; Touze, E ; Pico, F ; Corcia, P ; Doerner, T ; Steinhagen-Thiessen, E ; Baeckman, L ; Heekeren, HR ; Li, S-C ; Lindenberger, U ; Chan, A ; Hartung, H-P ; Aktas, O ; Lohse, P ; Kuempfel, T ; Kubisch, C ; Epplen, JT ; Zettl, UK ; Fontaine, B ; Vandenbroeck, K ; Matesanz, F ; Urcelay, E ; Bertram, L ; Zipp, F (BMJ PUBLISHING GROUP, 2012-09-01)BACKGROUND: Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently. METHODS: We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments. RESULTS: Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively). CONCLUSION: Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
ItemInterleukin-6 Gene Promoter-572 C Allele may Play a Role in Rate of Disease Progression in Multiple SclerosisYan, J ; Liu, J ; Lin, CY ; Csurhes, PA ; Pender, MP ; McCombe, PA ; Greer, JM (MDPI AG, 2012-10-01)Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system. Although the exact pathogenesis of MS is unknown, it is generally considered to be an autoimmune disease, with numerous genetic and environmental factors determining disease susceptibility and severity. One important mediator of immune responses and inflammation is interleukin-6 (IL-6). Previously, elevated levels of IL-6 in mononuclear cells in blood and in brain tissue from MS patients have been reported. Various polymorphisms in the promoter region of the IL6 gene have also been linked with IL-6 protein levels. In MS, several small studies have investigated whether two IL6 promoter polymorphisms (-597 G>A and -174 G>C) correlate with MS susceptibility, but with varying results. In the present study, we analyzed these polymorphisms, together with an additional polymorphism (-572 G>C) in 279 healthy controls and 509 patients with MS. We found no significant differences between MS patients and healthy controls for the different -597 or -174 IL6 promoter alleles or genotypes. There was a slight reduction in the percentage of individuals with MS who carried a C allele at position -572, although this was not significant after correction for multiple comparisons. Interestingly, however, the -572 C allele showed a significant correlation with the MS severity score, suggesting a possible role in disease progression.
ItemIdentity-by-Descent Mapping to Detect Rare Variants Conferring Susceptibility to Multiple SclerosisLin, Rui ; Charlesworth, Jac ; Stankovich, Jim ; PERREAU, VICTORIA ; Brown, Matthew ; TAYLOR, BRUCE ( 2012)