Clinical Outcome study for Dysferlinopathy: Characterisation of the onset and progression of hand muscle weakness in LGMDR2

Topic:

Clinical Trials

Poster Number: 328 T

Author(s):

Meredith James, PT PhD, JWMDRC, The Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Heather Hilsden, BA, JWMDRC, The Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, Heather Gordish-Dressman, PhD, Children's National Health System, John Day, MD, PhD, Stanford, Volker Straub, MD PhD, The Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, COS Consortium, COS Consortium, Laura Rufibach, PhD, Jain Foundation

Whilst limb-girdle muscular dystrophy R2- dysferlinopathy (LGMDR2) primarily affects muscles of the shoulder and pelvic girdle, impact on the muscles of the hands is under-recognised. Whilst previous studies have reported muscles of the hand are spared in LGMDR2, the lived experience of individuals with LGMDR2 indicated some individuals experienced significant functional impairment of their hands. COS2, an international two-year natural history study of 203 patients with LGMDR2/2B aimed to characterise disease progression and determine most appropriate clinical outcome assessments for clinical care and in clinical trials. At each study visit, upper limb assessments completed included the Performance of upper limb 2.0 (PUL), manual muscle testing (MMT) of the finger flexors, thenar eminence and the interrosei. Pinch and grip strength were measured using a CITEC hand-held dynamometer (HHD).

At all visits, in the nearly 66% of the cohort with finger flexor weakness, flexor digitorum profundus muscle (FDP) group was more affected than the flexor digitorum superficialis muscle with a median MMT of 4/5 vs 4+/5. The index finger FDP was most severely affected compared to the middle, ring and little finger FDP strength. Weakness was observed in palmar and dorsal interrosei and in some thenar muscles, particularly flexor pollicus longus (median MMT 4/5). We observed statistically significant reductions in pinch (Z=-4.153, p<.001) and grip strength (Z=-3.382, p<.001) over two years. Weakness of the hand was noted in some individuals with excellent shoulder function. At baseline visit, Spearman’s rank-order correlation showed a moderate association between PUL entry score and FDP median MMT score of the left and right hands, rₛ(199) = .56, p < .001. suggesting the upper limb may not follow a proximal to distal progression of muscle weakness in LGMDR2. Further longitudinal analysis will be completed. This is the first study to characterise the function of the hand in LGMDR2 and indicates assessment of the hands should be included as part of the standard clinical review of patients with LGMDR2, particularly the FDP muscles to ensure timely and appropriate management of hand function. This work was funded by the Jain Foundation