Skeletal muscle fiber function and rate of disease progression in amyotrophic lateral sclerosis.

The contractile properties of single muscle fibers reflect the functional status of muscle at the cellular level and have not been described in amyotrophic lateral sclerosis (ALS). Chemically skinned single muscle fibers (n = 173), obtained by needle biopsy from six men with ALS, were activated with Ca(2+), allowing maximal force measurements and specific force (SF) estimates. Maximum unloaded shortening velocity (V(o)) was determined using the slack test. The results were compared with muscle from healthy controls. Markers of disease progression included rate of change of ALS functional rating scale score, rate of change of forced vital capacity, and disease duration. Compared with controls, ALS patients had decreased whole muscle SF (measured by a combination of computerized tomography and isokinetic testing) but normal single fiber SF. The V(o) was greater for type I fibers in ALS. Patients with slower disease progression had increased single fiber size and a high percentage of hybrid fibers (expressing multiple myosin heavy chain isoforms). A needle biopsy obtained at the time of ALS diagnosis may assist with predicting rate of disease progression.