Three Year Natural History of Motor Impairment in Myotonic Dystrophy Type 1 (DM1) (P1.130)

Objective: Assess DM1 progression over 3 years using quantitative measures of motor function. Background: Few studies describe DM1 progression in large cohorts over long intervals. Methods: Single-center prospective study of ambulatory adult patients having non-congenital DM1 and greater than 100 CTG repeats. Evaluations of strength and function occurred at baseline, 1 year, and 3 years. 3 year data are described here. Results: We serially evaluated 60 patients (mean age 47 years, range 18 to 69 years, 42 females, mean CTG size 526) over 3 years. Timed function tests (TFTs) showed loss of motor performance but the magnitude of reduction was small. For example, 6 minute walk test (6MWT) distance was 415 meters at entry and decreased by an individual average of 5[percnt] at year 3, p u003c 0.001). Among TFTs, the greatest percentagewise changes were noted for 30 Foot Go ( 22[percnt] slowing, p u003c 0.0001 ) and ascending 4 stairs ( 24[percnt] slowing, p u003c 0.0001 ). The overall combined manual muscle testing (MMT) score showed a trend for decrease ( p=0.076 ), with distal muscles demonstrating the most change. Quantitative muscle testing (QMT) showed significant decrease in the strength of distal muscles. The mean reductions of ankle dorsiflexion and hand grip were 8[percnt] ( p u003c 0.23 ) and 7[percnt] ( p u003c 0.005 ), respectively. Conclusions: On average, the progression of muscle weakness and motor impairment over 3 years was modest. However, the extent of progression was variable between subjects, ranging from 56 m gain to 236 m loss in the case of 6 MWT. Further studies are needed to identify genetic factors or baseline characteristics that predict future progression. Many of the quantitative measures showed good reliability from baseline to 1 year, and may prove to be sensitive for detecting improvement in response to therapy. Disclosure: Dr. Eichinger has nothing to disclose. Dr. Pandya has nothing to disclose. Dr. Dekdebrun has nothing to disclose. Dr. Luebbe has nothing to disclose. Dr. Dilek has nothing to disclose. Dr. Martens has nothing to disclose. Dr. Heatwole has nothing to disclose. Dr. Thorton has received personal compensation for activities with Isis Pharmaceuticals as a consultant. Dr. Thornton has received research support from Isis Pharmaceuticals and Biogen Idec. Dr. Moxley has nothing to disclose.