[Influence of acute aggravations on the development of long-term handicap in relapsing remitting multiple sclerosis: a clinical study in 99 patients].
BACKGROUND
Rate of relapse occurring during the first 5 years of MS-RR is a prognosis factor of occurrence of disability or secondary progressive (SP) phase. Progressive phase, related to chronic axonal loss, is mainly considered as the principal factor of disability progression. Influence of acute relapses during the relapsing-remitting phase on disability development is not known as a prognosis factor.


OBJECTIVE
To determine the influence of the exacerbations among patients with RR-MS after the second clinical event on the disability occurrence.


METHODS
Diagnosis of multiple sclerosis was established according to Poser's classification. Disability measurement was made with the use of the Expanded Disability Status Scale (EDSS). The patients included in the study were classified as clinically definite RR-MS, with an EDSS score<or=3.5. The progressive phase was defined as the steady worsening of symptoms and signs for at least 6 months (Schumacher et al., 1965; Lublin and Reingold, 1996). The exacerbations were quoted and evaluated by a neurologist and the residual disability lasting at least 6 months after an acute event was measured with the EDSS. A score of 4.0 corresponds to limited walking ability, but without aid or rest for>500 m. The study began at the time of the second clinical event and ended when an EDSS score of 4.0 was reached or when a SP phase was beginning or at the last follow-up visit date if these two stages were not reached. The primary outcome measure was the comparison of the risk and the average time to reach an EDSS>or=4.0 or a SP form according to the annual exacerbation rate (AER) using Kaplan-Meier survival curve.


RESULTS
Among the 238 ms patients of the database, 136 patients were classified as having a definite RR-MS. Among these 136 patients, 99 patients could be included in the study according to the inclusion criteria. The median follow up of the patients since the first clinical event was 9.8 years (range 4 to 44). The average EDSS score was 0.7 at the beginning of the study and 2.3 at the end. 20.2p.cent of patients (n=20) reached an EDSS score of 4.0 or a SP-MS. The median AER was 0.4 and the average 0.62 (range 0 to 6.1). The time to reach the primary end point for 25p.cent of the population was 17.8 years in group with an AER<0.4 (group A) and 6.9 years in group with an AER>0.4 (group B) (logrank; p<0.0001). The relative risk for patients of the group B compared to group A to reach an EDSS of 4.0 or a SP form was 8.01 (IC-95p.cent: 2.74-23.46; p=0.0001).


CONCLUSIONS
In spite of a limited number of patients, this study gives evidence that a high rate of acute exacerbations in RR-MS patients after the second clinical event may be an independent predictive factor of long-term residual disability progression. High relapse rate leads to a more frequent and faster SP or EDSS>4.0 occurrence.
Gaillard
N
N
Service de Neurologie, CHU Carémeau, Nîmes.
Fabro-Perray
P
P
Faillie
J-L
JL
Le Bayon
A
A
Castelnovo
G
G
Dupeyron
A
A
Froger
J
J
Pelissier
J
J
Labauge
P
P
D000328:Adult; D006233:Persons with Disabilities; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications*; D013997:Time Factors