The Prognostic Value of Initial Relapses on the Evolution of Disability in Patients with Relapsing-Remitting Multiple Sclerosis

Abstract

The evolution of multiple sclerosis (MS) and the resulting disability are unpredictable. To identify clinical variables that could be potential prognostic factors, we followed a cohort of 288 patients diagnosed as having relapsing-remitting MS between 1990 and 2003. The end point was the first occurrence of a non-reversible EDMUS-GS score ≧3 (moderate disability). The impact of the number of MS attacks during the first 2 years of the disease as well as the first interattack interval were assessed in two Cox models, one using a fixed-in-time covariate, the other using a time-dependent covariate. Older age at onset and a higher number of MS attacks during the first 2 years of MS proved to be predictors of unfavourable prognosis. The first interattack interval had no influence on the evolution of the disability, conversely to the first relapse which had a short-term impact on the prognosis. We confirmed that the age at onset and the number of MS attacks during the first 2 years of MS are predictors of the evolution of the disability and demonstrated the importance of using time-dependent covariates.

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims

“…Measuring relapse incidence is also important in studies of disease progression and exacerbating factors. Such studies have shown that relapses may influence the progression of disability [11][12][13][14] and have explored factors, such as infection 15,16 and stress 17,18 , that place MS patients at risk for relapse 19 . Like research on precipitating factors, studies of relapse occurrence patterns and their relationships with baseline characteristics also rely on relapse identification 20 .…”

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis

“…15,16 Chronic demyelination, absence of remyelination, and progressive axonal loss are the pathologic hallmarks of progressive MS. 17,18 Onset of progressive disease course is agedependent rather than disease durationdependent and is the strongest determinant of poor long-term prognosis. 5,9,10,25,26 Incomplete recovery from individual relapses causes additional cumulative disability associated with poor long-term prognosis seemingly independent of progressive MS. [26][27][28] We hypothesize that complete to almostcomplete recovery from early relapses can potentially delay or prevent progressive MS onset. 5,9,10,25,26 Incomplete recovery from individual relapses causes additional cumulative disability associated with poor long-term prognosis seemingly independent of progressive MS. [26][27][28] We hypothesize that complete to almostcomplete recovery from early relapses can potentially delay or prevent progressive MS onset.…”

Prognostic Factors of Multiple Sclerosis in Lebanon

“…This might explain the lack of association between early disability onset and male gender or symptoms at onset, since the latter two variables tend to be associated with PPMS. Other studies with RRMS patients have similarly shown no such association (Binquet et al, 2006), while studies that grouped all MS cases together showed a significant predictive value for both variables (Confavreux, Vukusic, & Adeleine, 2003;Hammond et al, 2000). In a study grouping both populations, the significant association between symptoms at onset and time to disability, disappeared when controlling for initial course of the disease (Myhr et al, 2001).…”

“…This is the first study to identify such factors in the Arab population, using the Lebanese MS data base Project MS-Lebanon. Multiple studies, carried in western populations have consistently shown that the following factors were predictors of longer time to onset of disability: younger age at onset, female gender, complete recovery from the first relapse, onset with optic neuritis and no long tracts involvement, lower number of relapses during the first years of the disease, and longer period from disease onset to second relapse (Binquet et al, 2006;Hammond, McLeod, Macaskill, & English, 2000;Kantarci et al, 1998;Kurtzke et al, 1977;Mandrioli, Sola, Bedin, Gambini, & Merelli, 2008;Runmarker & Andersen, 1993;Weinshenker et al, 1991). Our results show that in Lebanese MS patients, the only two factors that significantly predict disability at 5 years are residual deficit after the initial attack and number of relapses during the first 5 years while gender, age at onset, type of symptoms at onset, and time to second relapse have no predictive value.…”