Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system that affects up to 1 million people in the United States and more than 2.5 million people worldwide (Wallin et al., 2019; Walton et al., 2020). MS predominantly affects women and follows either a relapsing-remitting or progressive clinical course (Lublin et al., 2014; Wallin et al., 2019). Muscle weakness is one of the most common symptoms of MS, worsens as disability progresses, and is strongly associated with declining mobility (Hoang et al., 2014; Mañago et al., 2017; Ramari et al., 2020). Muscle weakness in people with MS (PwMS) is typically considered a primary impairment resulting from inflammatory demyelination and neurodegeneration in the cerebral cortex and/or spinal cord (Compston and Coles, 2008). However, as MS is commonly diagnosed in early to middle adulthood, there can be additional adverse effects on skeletal muscle tissue such as atrophy and fatty infiltration due to secondary weakness from years or even decades of decreased mobility and physical activity (Karpatkin and Cohen, 2019; Motl, 2010). These morphological changes in muscle size and quality may be similar to changes seen in sarcopenia (age-related muscle loss typically found in older adults) (Petermann-Rocha et al., 2022) and may occur simultaneously with primary weakness in MS. Sarcopenia and accompanying muscle morphological changes have been strongly linked with worse muscle performance, mobility, and overall health for older adults (Pahor et al., 2009; Petermann-Rocha et al., 2022; Santilli et al., 2014; Xu et al., 2022). This link between muscle morphology and health related outcomes for persons with sarcopenia makes it crucial to better understand morphological changes in PwMS and how they are related to health outcomes.

Prior studies have reported muscle morphology impairments in PwMS such as decreased muscle mass and cross-sectional area (CSA) (Garner and Widrick, 2003; Kent-Braun et al., 1997; Ng et al., 2004; Wens et al., 2014). Importantly, strong relationships have been found between vastus lateralis CSA and quadriceps muscle strength in PwMS (Wens et al., 2014), and improvements in muscle fiber size have been reported following progressive resistance training in PwMS (Dalgas et al., 2010). Although these studies have provided important insights into muscle morphology in PwMS, they have used invasive and/or expensive methods (e.g., biopsy, magnetic resonance imaging) that are not always clinically available (Dalgas et al., 2010; Garner and Widrick, 2003; Kent-Braun et al., 1997; Ng et al., 2004; Wens et al., 2014). The use of more clinically practical measurement approaches might help facilitate the translation of muscle morphology assessment into clinical practice, and provide an important diagnostic tool for clinicians in addition to muscle performance and mobility outcomes.

Quantitative diagnostic ultrasound (sonography) is a non-invasive, inexpensive method to assess muscle morphology that offers potential for rapid translation into rehabilitation clinics. Sonography can provide reliable and valid measures of 1) muscle thickness, which can be used to identify muscle atrophy and hypertrophy, and 2) tissue echogenicity measured via grayscale analysis, which can be used to identify alterations in muscle tissue composition such as fatty infiltration (Harris-Love et al., 2016; Trip et al., 2009). Sonography applications are increasingly used in clinical and research activities in patients with sarcopenia (Harris-Love et al., 2014). and the feasibility of sonography to identify muscle morphology impairments has been demonstrated in PwMS (Gao et al., 2019; Kirmaci et al., 2021). In addition, recent evidence supports a direct relationship between thigh muscle weakness and thickness measured by ultrasound in PwMS (Kirmaci et al., 2021). While these early data support the potential utility of quantitative diagnostic ultrasound in PwMS, more research is needed to determine the ability of ultrasound to identify muscle morphology impairments, and to quantify their associations with force production, patient characteristics, and functional mobility in this population. Such information is important for development of targeted therapeutic interventions to address adverse muscle morphology changes and mitigate the effect on disability in PwMS.

The objectives of this study were to determine whether there are asymmetries in sonographic muscle morphology measures of the rectus femoris between more and less-involved limbs in PwMS, and to quantify relationships of muscle morphology measures with individual patient characteristics, muscle performance, and functional mobility. We hypothesized that measures of muscle morphology would be adversely affected in the more versus less involved limb, and that there would be significant associations between muscle morphology, muscle performance, and functional mobility.