Anne C. Feng

Seasonal Variations in Exacerbations and MRI Parameters in Relapsing- Remitting Multiple Sclerosis

Environmental factors may be involved in the etiology of multiple sclerosis (MS). We investigate prevalence of exacerbations and MRI findings in a cohort of relapsing-remitting multiple sclerosis patients, for evidence of seasonal variation or cyclic trends. We find only weak evidence of seasonality in our data. Differences in reports of seasonal variation in multiple sclerosis disease activity may be due to regional climatic differences or other geographic variables that change with latitude as well as genetic predisposition.

A Note on the Genome Scan Meta-Analysis Statistic

Wise and colleagues (Ann. Hum. Genet. (1999) 63: 263‐72) introduced a rank‐based statistical technique for meta‐analysis of genome scans, the Genome Scan Meta‐Analysis (GSMA) method. We provide an alternative derivation of the null distribution of the GSMA statistic, with extensions, and we suggest approximations to the distribution of the GSMA statistic that may be useful in applications.

A note on generalized Genome Scan Meta-Analysis statistics

BackgroundWise et al. introduced a rank-based statistical technique for meta-analysis of genome scans, the Genome Scan Meta-Analysis (GSMA) method. Levinson et al. recently described two generalizations of the GSMA statistic: (i) a weighted version of the GSMA statistic, so that different studies could be ascribed different weights for analysis; and (ii) an order statistic approach, reflecting the fact that a GSMA statistic can be computed for each chromosomal region or bin width across the various genome scan studies.ResultsWe provide an Edgeworth approximation to the null distribution of the weighted GSMA statistic, and, we examine the limiting distribution of the GSMA statistics under the order statistic formulation, and quantify the relevance of the pairwise correlations of the GSMA statistics across different bins on this limiting distribution. We also remark on aggregate criteria and multiple testing for determining significance of GSMA results.ConclusionTheoretical considerations detailed herein can lead to clarification and simplification of testing criteria for generalizations of the GSMA statistic.

Asymmetries in the spatial distributions of enhancing lesions and black holes in relapsing-remitting MS

Magnetic resonance imaging (MRI) is the most important paraclinical test in the diagnosis of multiple sclerosis (MS) and for delineating its natural history. We investigate MRIs from a longitudinal study of 24 relapsing-remitting MS patients who had monthly MRI examinations for one year, and were not receiving active MS therapy during this period. We hypothesized that lesions occur randomly throughout the brain, and that patients are homogeneous with regard to spatial patterns of lesion presentation. We recorded the numbers and locations of enhancing lesions and hypointense lesions (black holes) in all scans, and found asymmetrical patterns of lesions about the mid-transaxial, mid-coronal, and mid-sagittal planes. Furthermore, in distinct subsets of patients, enhancing lesions and black holes tend to occur in the same locations. Clustering in lesion locations may be of functional significance, with consequent therapeutic implications.