Glucocorticoid receptor gene polymorphisms associated with more aggressive disease phenotype in MS.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system, in which unknown environmental factors are thought to trigger disease in genetically susceptible persons. Glucocorticoids (GCs) play an important role in controlling chronic inflammatory diseases, like MS. Three polymorphisms in the glucocorticoid receptor (GR) gene (N363S, ER22/23EK and the Bcl I C/G) have been shown to alter glucocorticoid sensitivity, and therefore may influence disease course. We investigated the influence of these polymorphisms on clinical and MRI parameters. The ER22/23EK polymorphism was associated with a more aggressive MS phenotype, measured both clinically and on MRI.

Comparisons of patient self-report, neurologic examination, and functional impairment in MS.

OBJECTIVE: To compare the recently developed Guy's Neurologic Disability Scale (GNDS), based on patient self-report, with both neurologist rating of neurologic examination abnormalities using the Expanded Disability Status Scale (EDSS) and observations of functional impairment on the Multiple Sclerosis Functional Composite (MSFC) in the assessment of disease impact in MS. METHODS: Two hundred ninety MS patients were recruited at an outpatient clinic. Impairment and disability were assessed using GNDS, EDSS, and MSFC. Correlations between GNDS, EDSS, MSFC, and their corresponding components were studied for the total population, MS phenotypes, and three disability strata. RESULTS: Mean scores were 4.6 (SD, 2.0) for EDSS, 0.0 (SD, 0.8) for MSFC, and 14.6 (SD, 7.9) for GNDS. Good correlations were found between GNDS and EDSS (r = 0.73), between GNDS and MSFC (r = -0.68), and between different subcategories of the GNDS and EDSS, MSFC, and their corresponding components. Remarkably good correlations were found between lower limb function and all three scales. Poor correlations were also found, especially between different measurements focusing on cognitive function. CONCLUSION: The good correlations between GNDS and both EDSS and MSFC were mainly due to the importance of spinal-cord-related neurologic functions in all three scoring systems. A marked discrepancy was found for the assessment of cognition between objective measurements and subjective complaints. Because patients' self-reporting correlates well with results of physical examination, GNDS can offer a valuable way to measure disease impact in MS. However, GNDS is not an adequate screen of cognitive dysfunction.