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From the Department of Neurology (Dr. Marrie), Cleveland Clinic Foundation, OH; Department of Biostatistics (Dr. Cutter), University of Alabama at Birmingham; Division of Neurology (Drs. Tyry, Campagnolo, and Vollmer), Barrow Neurological Institute, Phoenix, AZ; and Department of Neurology (O. Hadjimichael), Yale University Medical School, New Haven, CT.
Address correspondence and reprint requests to Dr. Ruth Ann Marrie, Mellen Center for MS Treatment and Research, U10, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: marrier{at}ccf.org
Objective: With diagnostic criteria alterations, increased MRI availability, and awareness of therapies, temporal changes in incidence and prevalence rates may occur, with an increase in the proportion of mildly affected persons diagnosed with multiple sclerosis (MS). The authors assessed temporal trends in the delay from symptom onset to diagnosis (DONDX), and determined whether the degree of disability at diagnosis differs by year of symptom onset (YONSET), using the NARCOMS Registry.
Methods: The authors selected US participants with an age at symptom onset of 10 to 60 years, and YONSET 
1980 (n = 16,581). The authors divided YONSET into 5-year groups and compared DONDX between groups using multivariate Cox regression. The authors classified participants enrolled within 2 years of diagnosis (n = 5,548) as having mild, moderate, or severe disability using Patient Determined Disease Steps, and assessed the association of disability with YONSET using polytomous logistic regression.
Results: DONDX decreased with later YONSET (r = –0.43, p < 0.0001). This association remained after adjustment for demographic factors in a multivariate Cox model. Later YONSET was associated with increased odds of having mild disability at diagnosis as compared to severe disability (OR = 1.10 per year; 1.09 to 1.11).
Conclusion: The delay from symptom onset to diagnosis is steadily decreasing in MS. An increasing proportion of patients with MS have mild disability at diagnosis after accounting for confounders. As the effectiveness of therapies is influenced by disease duration, this has implications for comparison of treatment effects in modern clinical trials to earlier study results.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the October 11 issue to find the title link for this article.
The NARCOMS Registry receives support from the Consortium of Multiple Sclerosis Centers.
Disclosure: The authors report no conflicts of interest.
Received February 2, 2005. Accepted in final form June 15, 2005.
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