Neuromuscular Disorders: Clinical and Functional Measurements

Outcome measures are the cornerstone of advancing care and research in neuromuscular medicine, providing essential tools to evaluate disease progression, therapeutic efficacy, and clinical decision-making. Outcome measures ought to bridge the gap between the rigor of research and the reality of the clinic to ensure that what researchers measure truly matters to individuals being treated.  In a field marked by heterogeneous disorders such as amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG), and muscular dystrophies, standardized and sensitive metrics are critical to harmonizing clinical research and practice. As novel therapies evolve, collaborative efforts to refine patient-reported outcome measures (PROMs) and address unmet needs (eg, standardization, sensitivity to subtle changes, inclusivity for rare diseases) are pivotal in shaping patient-centered neuromuscular care. There is growing interest in developing more sensitive and responsive disease-specific outcome measures and biomarkers as most generic outcomes often fail to capture nuanced patient experiences and variability in endpoints across trials complicates data analysis. This issue of Practical Neurology highlights the current state of the art in such surrogate endpoints.

PROMs have emerged as important instruments to bridge the divide between clinical research and practice by prioritizing the patient’s voice in assessing symptoms, function, and quality of life. Drs. Kelly, Nawaz, and Gwathmey begin this issue with an overview of common PROMs in neuromuscular diseases. The authors highlight over 30 different PROMs that support investigations in ALS, peripheral neuropathy, MG, and myopathy. Although these patient-reported changes are important for assessing therapeutic benefit, it is not always clear how a change in a PROM scale correlates to clinical change. This article highlights the strengths and weaknesses of various PROMs.

Drs. Uysal and Sadjadi introduce the concept of minimal clinically important difference (MCID) as one of the methods of interpreting outcome measure changes. They provide an overview of both anchor- and distribution-based methodologies and discuss how to determine an MCID along with key limitations of these emerging measures.

After a discussion of outcome measures, the issue shifts toward objective measures of change through the lens of various standard and emerging biomarkers. Drs. Ziff and Morrow review the longitudinal changes in MRI of muscle and nerve in individuals with myopathy and neuropathy along with beautiful example images. 

Next, Drs. Geronimo and Johnson discuss the current state of the art of digital biomarkers for neuromuscular disorders. These biomarkers involve the collection of data through wearable devices and sensors. Their review includes an overview of digital biomarkers in ALS, muscular dystrophy, and MG, including their limitations and future directions. 

This issue concludes with an article by Drs. de Castro, Schneider, Zinman, and Abrahao which details the current and emerging cerebrospinal fluid and serum biomarkers in ALS. In addition to discussing the well-known use of neurofilament light chain, they highlight emerging biomarkers such as inflammation-associated markers and glial acid fibrillatory protein. Finally, in a preview of what may be used for other inherited neuromuscular disease, they discuss mutation-specific markers in familial ALS. 

We are exceedingly grateful to all the authors for their contributions to this issue. By highlighting the advances in PROMs and biomarkers, we hope to provide more tools for future clinical trials and surrogate outcomes. With such tools, therapies may be more successfully identified which help clinicians translate the growing knowledge of the pathophysiology of neuromuscular disease into treatment options.