Background: The eight Performance Scales and three assimilated scales (PS) used in North American Research Committee on Multiple Sclerosis (NARCOMS) registry surveys cover a broad range of neurologic domains commonly affected by multiple sclerosis (mobility, hand function, vision, fatigue, cognition, bladder/bowel, sensory, spasticity, pain, depression, and tremor/coordination). Each scale consists of a single 6-to-7-point Likert item with response categories ranging from " normal" to " total disability" Relatively little is known about the performances of the summary index of disability derived from these scales (the Performance Scales Sum or PSS). In this study, we demonstrate the value of a combination of classical and modern methods recently proposed by the Patient-Reported Outcome Measurement Information System (PROMIS) network to evaluate the psychometric properties of the PSS and derive an improved measure of global disability from the PS.Methods: The study sample included 7,851adults with MS who completed a NARCOMS intake questionnaire between 2003 and 2011. Factor analysis, bifactor modeling, and item response theory (IRT) analysis were used to evaluate the dimension(s) of disability underlying the PS; calibrate the 11 scales; and generate three alternative summary scores of global disability corresponding to different model assumptions and practical priorities. The construct validity of the three scores was compared by examining the magnitude of their associations with participant's background characteristics, including unemployment.Results: We derived structurally valid measures of global disability from the PS through the proposed methodology that were superior to the PSS. The measure most applicable to clinical practice gives similar weight to physical and mental disability. Overall reliability of the new measure is acceptable for individual comparisons (0.87). Higher scores of global disability were significantly associated with older age at assessment, longer disease duration, male gender, Native-American ethnicity, not receiving disease modifying therapy, unemployment, and higher scores on the Patient Determined Disease Steps (PDDS).Conclusion: Promising, interpretable and easily-obtainable IRT scores of global disability were generated from the PS by using a sequence of traditional and modern psychometric methods based on PROMIS recommendations. Our analyses shed new light on the construct of global disability in MS.