THE NATURAL-HISTORY OF AMYOTROPHIC-LATERAL-SCLEROSIS AND THE USE OF NATURAL-HISTORY CONTROLS IN THERAPEUTIC TRIALS

We analyzed the natural history of amyotrophic lateral sclerosis in 27 7 patients. Our goal was to develop a better understanding of the clin ical disease and thus improve the design of therapeutic trials. The Tu fts Quantitative Neuromuscular Exam (TQNE) was used as the primary ass essment instrument. Our analysis suggested that although more observat ions are desirable, six monthly TQNEs were adequate to establish the r ate of disease progression. We observed a spectrum of deterioration ra tes without definable subgroups. The striking linearity of deteriorati on was confirmed. We found a high correlation between deterioration ra tes in arm and leg strength for individual patients, but a wide range between different patients. Sex and the age at clinical onset did not affect the deterioration rate. As compared with patients without a pos itive family history, those with other affected family members had a s lower loss in arm but not leg strength. We propose that natural histor y controls can be used effectively in the design of ALS therapeutic tr ials.