Longitudinal Progression of Edema and Fatty Replacement of Lower Extremity Muscles in FSHD

Update: Additional paper published 29-May-2013: Longitudinal Features of Stir Bright Signal in FSHD

Update: Additional review paper published 16-Dec-2011: Skeletal Muscle Edema in Muscular Dystrophy: Clinical and Diagnostic Implications

Seth Friedman, Ph.D.
Seth Friedman, Ph.D.

Grant distributed November 18, 2011.


Seth Friedman, Dennis Shaw, et. al.

Degeneration of muscles in FHSD is associated with fatty replacement on magnetic resonance imaging (e.g. Olsen 2006). Quantification of this fatty change has been posited as a potential biomarker of disease in anticipation of intervention trials (Kan 2009). Older pathologic literature and current work (Frisullo 2010) have shown evidence of inflammation pathologically, and elevated inflammatory markers in patients with muscles demonstrating edema on MRI. This work will build on our previous funded work describing the heterogeneity and distribution of edema and fat in calf within 15 FSHD patients (Muscle and Nerve article The MRI spectrum of Fascioscapulohumeral Muscular Dystrophy (FSHD)). This current proposal seeks to obtain longitudinal imaging data in calf and thigh, with the aim of determining the temporal pattern of edematous and fatty changes in the muscle observed in the earlier study. As we expect we will recruit an overlapping set of subjects from the original study, we will have longer-term data in the calf.

Dennis Shaw, M.D.
Dennis Shaw, M.D.

Imaging measures will be correlated to quality of life and functional indices. A third aim is proposed to look at peripheral blood inflammatory markers that have been reported in recent studies. Defining the muscle imaging patterns seen in FSHD will contribute to the understanding of the pathophysiology as to how the muscle is injured by the disease. This will then also be important in measuring the impact of interventions in future treatment trials.

— Dennis Shaw, Seth Friedman

Figure 1
Figure 1. Notable calf imaging features in patients with FSHD. Top row of each patient are T1-contrast images, bottom row are short tau-inversion recovery (T1) images. In the first pair of panels, T1/STIR images are shown at two positions in the lower leg of one patient (#9). Marked differences in the degree of fatty replacement and edematous signal are shown progressing distal to proximal. In the bottom left pair, Patient 10 demonstrates progressed fatty replacement in almost all muscles. Notably, spared bundles of muscle are observed even in highly affected muscles. In the bottom right pair, a patient (#15) with advanced age demonstrates an edema and fatty replacement in the tibialis posterior, a muscle not affected in earlier stages of the disease.

See Grant: Longitudinal Progression of Edema and Fatty Replacement of Lower Extremity Muscles in FSHD