Reaching Expanded Disability Status Scale Research Articles

Will Rogers phenomenon in multiple sclerosis

Using different criteria for classifying patients into various stages of a disease can modify the stage-specific prognosis, even though the overall disease course remains unchanged. This is known as the "Will Rogers phenomenon," precluding the use of historical controls for treatment trials. We assessed whether the Will Rogers phenomenon may affect multiple sclerosis (MS) prognosis when applying different diagnostic criteria. Patients with a clinically isolated syndrome (CIS) suggestive of MS were studied. After 1 year, each patient was classified as CIS or evolved to MS according to two diagnostic criteria (Poser and McDonald). The outcome for prognosis was the time to reach an Expanded Disability Status Scale score > or = 3.0. 309 patients were studied for a median period of 84 months. After 1 year, 16% of patients had MS according to Poser and 44% according to McDonald criteria. The probability to reach Expanded Disability Status Scale score > or = 3.0 at median follow-up was 11% in CIS patients according to Poser and 7% according to McDonald criteria; it was 46% in MS patients according to Poser and 27% acccording to McDonald criteria. The group with a discordant diagnosis had a worse prognosis than that of CIS patients according to both criteria (p = 0.01), but better than that of MS patients according to both criteria (p = 0.01). The use of different diagnostic criteria may generate spurious improvements in the medium-term prognosis of MS. This calls for caution in using historical controls for MS trials.

Is late-onset multiple sclerosis associated with a worse outcome?

To describe the characteristics of late-onset multiple sclerosis (MS) (LOMS, 50+ years) vs adult-onset MS (AOMS, 16 to <50 years) and examine prognosis and associated risk factors. Patients with definite MS, onset prior to July 1988, registered with a BCMS clinic before July 1998, with at least one Expanded Disability Status Scale (EDSS) score, were selected from the longitudinal population-based British Columbian (BC) MS database. Clinical and demographic characteristics were compared between LO and AOMS. Progression was measured as time to reach sustained EDSS 6 and potential risk factors examined were sex, disease course (primary progressive [PP] vs relapsing [R]), and onset symptoms. Of those eligible (n = 2,837), LOMS comprised 132 (4.7%), with PPMS predominating (54.5% vs 10.6% in AOMS, p < 0.0005). Motor onset symptoms were more prevalent in LOMS and sensory and optic neuropathy more prevalent in AOMS (p < 0.0005). AOMS averaged 27.7 years (95% CI: 26.3 to 29.1) to EDSS 6 from onset vs 16.9 years (95% CI: 9.0 to 24.8) in LOMS, p < 0.0005. However, AOMS was associated with a younger age at EDSS 6 (58.4 years [95% CI: 57.1 to 59.6] vs 71.2 years [95% CI: 65.2 to 77.3] in LOMS, p < 0.0005). There were no differences in progression between AO or LO for those with PPMS (p = 0.373) or R-MS (p = 0.438), although considerable variation was observed. Late-onset multiple sclerosis (LOMS) is not necessarily associated with a worse outcome: first, progression in the primary progressive or relapsing patients differed little between late-onset vs adult-onset; secondly, those with LOMS were older when reaching Expanded Disability Status Scale 6. The disease course has a far greater implication for disease prognosis than the presence of LOMS.

Age-related disability in multiple sclerosis.

There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital-based cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person-years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan-Meier method with age as a categorical time-varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age-adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.