Assessing Dysferlinopathy Patients Over Three Years With a New Motor Scale

Abstract

Objective Dysferlinopathy is a muscular dystrophy with a highly variable clinical presentation and currently unpredictable progression. This variability and unpredictability presents difficulties for prognostication and clinical trial design. The Jain Clinical Outcomes Study of Dysferlinopathy aims to establish the validity of the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scale and identify factors that influence the rate of disease progression using NSAD. Methods We collected a longitudinal series of functional assessments from 187 patients with dysferlinopathy over 3 years. Rasch analysis was used to develop the NSAD, a motor performance scale suitable for ambulant and nonambulant patients. Generalized estimating equations were used to evaluate the impact of patient factors on outcome trajectories. Results The NSAD detected significant change in clinical progression over 1 year. The steepest functional decline occurred during the first 10 years after symptom onset, with more rapid decline noted in patients who developed symptoms at a younger age (p = 0.04). The most rapidly deteriorating group over the study was patients 3 to 8 years post symptom onset at baseline. Interpretation The NSAD is the first validated limb girdle specific scale of motor performance, suitable for use in clinical practice and clinical trials. Longitudinal analysis showed it may be possible to identify patient factors associated with greater functional decline both across the disease course and in the short‐term for clinical trial preparation. Through further work and validation in this cohort, we anticipate that a disease model incorporating functional performance will allow for more accurate prognosis for patients with dysferlinopathy. ANN NEUROL 2021;89:967–978

Three‐year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy

“…Clinical symptoms usually start between late teenage years and 30 years and are associated with elevated serum creatine kinase (CK) levels 1,3 . The rate of disease progression is variable and is generally faster when the disease begins during early teenage years 4 . Whereas skeletal muscle is highly affected, impacting daily life activity, involvement of cardiac muscle is uncommon in dysferlinopathy 4 …”

Cardiac and pulmonary findings in dysferlinopathy: A 3‐year, longitudinal study

“…To correlate heart and respiratory measures with skeletal muscle function, we used the North Star Ambulatory Assessment for limb girdle type muscular dystrophy (NSAD score) 16 . This scale was adapted from the a‐NSAA for use in ambulant and non‐ambulant patients with dysferlinopathy.…”

“…15 To correlate heart and respiratory measures with skeletal muscle function, we used the North Star Ambulatory Assessment for limb girdle type muscular dystrophy (NSAD score). 16 This scale was adapted from the a-NSAA for use in ambulant and non-ambulant patients with dysferlinopathy. The NSAD scale was validated using the baseline visits in the Jain COS study and was then used to provide direct motor assessment scores by experienced physiotherapists for subsequent assessments.…”

Assessing the Relationship of Patient Reported Outcome Measures With Functional Status in Dysferlinopathy: A Rasch Analysis Approach

“…The NSAD is a Rasch-developed clinician reported outcome (ClinRO) of motor performance suitable for ambulant and nonambulant adults and children, validated in this dysferlinopathy (LGMDR2) cohort, and has been shown to be very sensitive to change over 1 year ( 15 ).…”

“…The Jain Clinical Outcomes Study (COS) for dysferlinopathy was established to address the lack of comprehensive natural history data for dysferlinopathy, particularly around PROMs, and to identify if these were associated with functional changes related to disease progression. The aim of the present paper is to evaluate the suitability and change of selected PROMs from baseline up to a maximum of 4 years and to examine the association between these measures and the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) ( 15 ) and the Performance of Upper Limb (PUL) ( 16 ), both as measures of motor performance.…”