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Mortality studies for multiple sclerosis: still a useful tool to analyse long-term outcome
  1. Paolo Ragonese
  1. Correspondence to Dr Paolo Ragonese, Departments of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, via G. La Loggia, 1, Palermo 90129, Italy; paolo.ragonese{at}

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Mortality from multiple sclerosis: cautious optimism for the future or just the effects of a relationship between the changing of diagnostic criteria for multiple sclerosis and long-term outcome measures

Mortality studies represent a useful way to look at the prognosis of a chronic complex disease and to evaluate the impact of therapeutic and caring strategies on long-term outcomes. Results should be interpreted keeping always in mind the following important aspects: first, to what extent the disease affects patient’s life in terms of life expectancy. Second, what is at this moment the real impact that the strategies and measures we adopt to cure and to take care of patients really have on clear and strong endpoints like mortality? In their JNNP manuscript, Lunde et al.1 show a significant reduction in life expectancy in people affected by multiple sclerosis (MS) over a study period of about 60 years. The study, also showing an overall nearly threefold increased mortality risk compared with the general population, is consistent with previous reports.2 Looking at the results of the present study, what appears to be most interesting is the decline in the standardized mortality rate (SMR) throughout the considered study periods, that in the last period of time (1997–2012), showed mortality rates almost similar to that of the general population. It may appear strikingly encouraging at a first glance, but this aspect must be considered more carefully. In fact, as the authors clearly reported in the paper, the last cohort of patients represents a distinct subgroup for several reasons. The number of people dying from the disease declined as expected throughout the years. Hence, the observed rates are less accurate due to a smaller number of deaths. One may otherwise assume that treatment available since the early 90s would have an impact in reducing mortality, but to accept this assumption it should be necessary that treatment strategies should have been applied homogeneously. Finally and possibly most important, in past years, diagnostic criteria changed several times. At the same time as reported in many studies as well as in the present, a consistent decline occurred in time from onset of symptoms to diagnosis. Many studies have already indicated how an anticipation in time to diagnosis often correspond to the observation of an improved prognosis (Will Roger’s phenomenon). In the specific case of MS survival, it may depend on the inclusion of milder cases with a better prognosis. Alternatively, several studies indicated that shortening the time to initiate a therapy could have a positive effect in delaying the time to reach a higher disability and it has been accepted now as a standard approach. To support this view, a study suggests that this could also determine an overall reduced mortality risk.3 However, we ought to consider that most of the studies indicated that the majority of mortality burden is related to increasing age and disease duration. In this case, it may be argued that more attention to the accumulation of comorbid disorders and better supportive cures may exert the strongest impact in delaying mortality. The different SMR observed between women and men may be interpreted in this perspective. It may depend again on differences in comorbidities or life style factors as the authors report but at the same time, women with higher ages and higher disability may also be in the condition of a reduced opportunity to have access to cures. This may not be the case of Norway, of course, but it should be considered in studies from other countries. Reported causes of deaths in mortality studies give us information on the strength of the disease in the observed increased mortality risk. Anyway, the limit of these data depends on the fact that we usually do not have much information regarding the period preceding death, and death certificates are not accurate. Therefore, there is still a gap to bridge in our knowledge; this would allow us to increase the level of certainty about the effects of therapeutic intervention in delaying MS-related deaths. Finally, the paper reports a dramatic difference in life expectancy between patients with MS having a progressive disease course and patients with a relapsing remitting disease. The observed difference in life expectancy outline the needto enhance any effort in supporting research that could provide new strategies to cure primary progressive MS.


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  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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