Nusinersin Does Not Mitigate Hip and Spine Pathoanatomy in Spinal Muscular Atrophy Patients

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Medicine and Health Sciences


Spinal muscular atrophy (SMA) consists of a group of neuromuscular disorders characterized by degeneration of alpha motor neurons, leading to a lower motor neuron-type syndrome. Children afflicted with SMA 1 and 2 are prone to abnormal musculoskeletal growth and deformities affecting axial/appendicular skeleton. Nusinersin is an antisense oligonucleotide therapy administered intrathecally for the duration of the patient’s life with proven benefits of partially maintained muscle strength and respiratory function. The effect of Nusinersin to mitigate developing skeletal deformities, namely the occurrence and progression of scoliosis and hip instability (coxa valgus, acetabular dysplasia) has not been evaluated. We hypothesize SMA patients receiving Nusinersin treatment will have lower incidence/progression of scoliosis and hip instability, less need for surgical correction in proportion to age/motor growth remaining at the time therapy was initiated, compared to similar cohort not treated w/ Nusinersin. 44 subjects with SMA2 were analyzed with a median age at baseline of 4.2 years (range, 1.3-23.9 yrs) and were followed for a median of 7.0 yrs (range, 1.2-14.5 yrs) to a median age of 11.7 yrs (range, 4.1-36.3 yrs). 22 subjects (43%) were treated with Nusinersin for a minimum of 1 year (median 2.2 yrs; range, 1-6.6 yrs). Consecutive radiographs were measured to document the presence/progression of scoliosis and hip instability using Cobb and Migration Index respectively. Established pathoanatomic thresholds for recommending surgical intervention of spine/hip were used to assess failure of Nusinersin. Subjects in Nusinersen group were younger (median, 2.5 vs 6.8 yrs; p=0.001) and had smaller curves at baseline (median, 11° vs 20°; p=0.02). 13/23 subjects untreated with Nusinersen without respiratory assist at baseline, required respiratory assistance at end of follow-up (p<0.001). 9/17 Nusinersen subjects without respiratory assist at baseline, required it at the end of follow-up (p=0.008). No difference in scoliosis progression between pre- vs post-Nusinersen treatment in absolute change (p=0.54) or annual change in Cobb angle (p=0.57). No difference in scoliosis progression between treated vs. untreated SMA patients at any point during follow-up with respect to absolute change (p=0.15) or annual change in Cobb angle (p=0.23). Of 19 patients treated w/ Nusinersen, 15 had serial hip radiographs and of 25 untreated subjects, 11 had serial hip radiographs. All SMA patients had significant hip instability regardless of treatment. Patients with SMA benefit from improved muscle strength in proportion to the neuromotor growth remaining at the time treatment is instituted, treatment with Nusinersin did not ameliorate the skeletal manifestations: scoliosis, parasol rib deformity, hip instability progressed independent of the age that treatment was instituted.


Copyright 2019 all authors


Michael J. Troy 1, 2, Patricia E. Miller,1, Basil Darras1, Brian Snyder1

1* Boston Children's Hospital, Boston, MA; 2* Marian University College of Osteopathic Medicine, Indianapolis, IN

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