NATURAL-HISTORY OF AMYOTROPHIC-LATERAL-SCLEROSIS IN A DATABASE POPULATION - VALIDATION OF A SCORING SYSTEM AND A MODEL FOR SURVIVAL PREDICTION

Over 1200 patients with motor neuron disease have been carefully diagn osed, followed, and included in a detailed database delineating charac teristics of the disease. Of these patients, 831 were identified as ex hibiting typical sporadic amyotrophic lateral sclerosis (ALS). The pro gression of the disease in these patients has been followed with our s coring system and the ALS score was verified as a significant covariat e of survival. Age at first symptom, delay from first symptom to enter ing ALS clinic, and rate of change of respiratory function were also i dentified as significant covariates of survival. These measures, appli ed to the Cox proportional hazards model, were used to develop a mathe matical model for prediction of survival time in ALS, which proved hig hly accurate for the 80% of patients at intermediate risk. For those p atients, a second model was developed which accurately predicts, after an initial period of observation, the time over which ALS patients wi ll decline a set number of points in total ALS score. Such validation permits initial trials for drug therapies in ALS by comparison of rela tively small groups of treated patients to this historical control gro up, based on the model of predicted time to a particular decrement in fetal ALS score.