Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process
Confavreux C,Vukusic S and Adeleine P;
Commented by , 30 Apr 2003
Background
Although clinical markers have been identified predicting the initial course of multiple sclerosis (MS), counseling with regard to long term prognosis is often difficult. For the individual MS patient, the concern is mostley focused on time to advanced stages of disability, e.g. need for gait aid or weelchair, but little is so far known about predictive factors of disability in this regard.
Aim
To determine if the predictive value of clinical variables still have an effect after the first stages of disability have been reached.
Methods
The authors collected their data from a unique database (EDMUS), where patients with a diagnosis of MS have been registered since 1957. By april 1997, a cohort of 2021 patients had been included. The authors used the Kurtzke Disability Status Scale as a reference for neurological disability. The score ranged from 0 – 10 (no neurologic disability – death).
A score of 4 corresponds to walking ability for more than 500 m without aid or rest; a score of 6 to walking ability for less than 100 m with unilateral support and no rest; and a score of 7 to walking ability for less than 10 m with support and no rest. Kaplan-Meier survival analysis was used for statistical evaluation, and end points were time to scores of 4, 6 and 7. Survival curves were compared using log-rank test.
Results
Clinical variables assessed early in the disease were strong predictors of time from onset to irreversible disability. The factors were:
- Gender.
- Age.
- Initial symptoms and course of the disease.
- Degree of recovery from the first relapse of the disease.
- Time from MS onset to the second neurologic episode.
- Number of relapses during the first five years of the disease.
- Time from MS onset to Kurtzke Disability Status Scale score 4.
Once this score had been reached, the variables were no longer predictive of subsequent disability progression. In a subgroup of patients with primary progressive disease, clinical variables were not predictive with regard to disability score of 4, 6 and 7.
Discussion
The study shows that clinical variables, assessed early in relapsing-remitting MS (RRMS), predict time to irreversible disability. This was not true for subsequent disability progression. The authors speculate if MS is a two-stage disease, with an initial phase of variable duration, and a final invariant common pathway, amnesic to the clinical history.
This hypothesis is supported by the observation, that the disease is characterized by a RR course untill score 4, while the following development of symptoms are progressive. The results therefore suggest that acute inflammation in RRMS may have a limited effect on the relentless neurodegeneration that characterizes the progressive course.
What the authors do not comment, is that the Kurtzke Disability scale is bimodal, where a score of 4 changes the evaluation from accumulation of neurologic symptoms to a primary focus on gait function. In this way it is possible that the authors to some extent have described the scale, instead of describing the disease.