The loss of ambulation is one of the key characteristics of Duchenne muscular dystrophy (DMD) and represents a major challenge for patients and caregivers alike. Studies have indicated that corticosteroid-naive patients begin using a wheelchair at a median age of 10 years. Patients on corticosteroid therapy usually experience a delay of a mere 2 to 4 years.
Most research on DMD seeks to trace the trajectory of motor and respiratory function outcomes. The reality is that there is high heterogeneity in the presentation of patients with DMD, and this makes the design of any clinical trial a challenge. There is also the question of whether a focus on ultimate outcomes (such as a loss of ambulation or respiratory ability) causes clinical researchers to miss out on other important disease milestones.
In Developmental Medicine & Child Neurology, Zambon and colleagues conducted a study to assess 2 motor parameters in patients with DMD: the North Star Ambulatory Assessment (NSAA) score and timed rise from floor. The NSAA is a 34-point functional scale for patients with DMD. In typically developing males, NSAA scores typically peak at 4 years of age; in patients with DMD, this is delayed by 2-3 years, after which the score plateaus and later declines.
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Two Key Parameters
The authors of this study retrospectively recruited patients through the DMD UK NorthStar Network, a nationwide network in the UK that consists of 23 neuromuscular centers. Patients who were exposed to drugs that could potentially affect ambulation and those with substantial learning difficulties were excluded from this study.
Read more about DMD etiology
In addition to assessing participants on these 2 parameters, the research team also reviewed individual longitudinal corticosteroid treatment. They classified the patients’ corticosteroid regime as either “predominantly daily” or “predominantly intermittent.” The benchmark was the recommended daily dose pro-kilo for prednisolone and deflazacort being 0.75 mg/kg and 0.9 mg/kg respectively.
The research team reviewed 293 patients from 13 different neuromuscular centers. A total of 160 patients lost ambulation, with 22 experiencing a long bone fracture within 6 months before loss of ambulation. Patients who were on corticosteroids “predominantly daily” had a 41% reduction in the risk of losing ambulation than those who were on corticosteroids in a “predominantly intermittent” manner.
Zambon and colleagues also reported that patients with DMD achieved their highest NSAA score at a mean age of 6 years and 10 months. Patients with a NSAA score between 22 and 25 points had a 26% increased risk of losing ambulation.
In terms of timed rise from floor, the research team reported that a faster time at baseline was significantly associated with an older age at which loss of ambulation occurs. Patients who were able to rise from the floor in less than 3.5 seconds lost their ability to ambulate around the median age of 14. The slower the timed rise from floor, the sooner patients lose their ability to ambulate.
“In conclusion, both NSAA and [timed rise from floor] recorded at the age of expected peak are significant determinants of age at [loss of ambulation] in male children with DMD, the latter being more important even when recorded early in the disease course,” the authors of the study concluded.
The Caregiver Burden
The study above indicates that various parameters exist in predicting the age at which an individual with DMD loses their ability to ambulate. These objective measures can help clinicians plan for eventual disability and offer appropriate support.
Another means by which physicians can gauge disease impact is using patient-reported outcomes. This differs from the rigid structure of yes/no questionnaires and scores in that they depend on the subjective experiences of patients in reporting how disease progression affects their lives.
“The introduction of person-reported outcomes (PROs) over the past few decades has facilitated clinical research in many ways,” Schwartz and colleagues wrote in the Orphanet Journal of Rare Diseases. “PROs make it increasingly feasible for the patient’s voice to be heard in important studies of great relevance to them.”
Schwartz and colleagues set out to understand the DMD patient experience by inviting participants to offer their views on DMD care (n=521). Participants were caregivers to a family member with DMD of at least 2 years of age, usually their son. Participants were recruited via Rare Patient Voice, a patient advocacy group, as well as by word of mouth.
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The research team interviewed participants to understand relevant aspects of DMD care. To holistically assess the disability experiences of patients with DMD, the research team sought to cover multiple angles, including sleep disturbances and peer-to-peer relationships.
The results of the study demonstrated concerns by caregivers across a variety of domains, including fatigue impact, strength impact, depressive symptoms, and psychological stress. Because the study is focused entirely on caregivers and not patients directly, it highlights the great number of challenges that caregivers face in their daily lives, something that can be easily overlooked in a clinical setting.
In conclusion, both objective and subjective measures of DMD disability are important in helping clinicians devise a holistic care package that meets the needs of both patients and their caregivers. The question is, in the midst of the hustle and bustle of medical life, are we as physicians willing to slow down to ask relevant questions in order to understand where the real needs lie?
References
Zambon AA, Ayyar Gupta V, Ridout D, et al. Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy. Dev Med Child Neurol. 2022;64(8):979-988. doi:10.1111/dmcn.15176
Schwartz CE, Stark RB, Cella D, Borowiec K, Gooch KL, Audhya IF. Measuring Duchenne muscular dystrophy impact: development of a proxy-reported measure derived from PROMIS item banks. Orphanet J Rare Dis. 2021;16(1):487. doi:10.1186/s13023-021-02114-7
