Disease progression and survival in ALS: first multi-state model approach.

Although several prognostic factors have been identified in ALS, there remains some discordance concerning the prognostic significance of the age and clinical form at onset. In order to clarify these findings, we have analysed already known prognostic factors using a multi-state model. Two hundred and twenty-two sporadic ALS patients were followed. A simple unidirectional three-states model was used to summarize clinical course of ALS. States 1 and 2 reflected the progression of neurological impairment and state 3 represented the end of follow-up (tracheotomy or death). Gender, diagnostic delay, body mass index (BMI) and slow vital capacity (SVC) were also recorded. A time-inhomogeneous Markov model with piecewise constant transition intensities was used to estimate the effect of the covariates in each transition. The bulbar form at onset was only correlated with a more rapid clinical progression between state 1 and state 2. In contrast, an advanced age at diagnosis affected only survival from state 2. This methodological approach suggests that these two factors have a different prognostic significance: age at onset is related to patient's survival and the clinical form at onset predicts the progression of motoneuronal impairment in different regions.