Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen

Alessandra Govoni MD, Giulia Ricci MD, PhD, Silvia Bonanno MD, PhD, Luca Bello MD, PhD, Francesca Magri MD, Megi Meneri MD, Francesca Torri MD, Claudia Caponnetto MD, Luigia Passamano MD, Marina Grandis MD, Francesca Trojsi MD, Federica Cerri MD, Giulio Gadaleta MD, Giuliana Capece MD, Luca Caumo MD, Raffaella Tanel MD, Elena Saccani MD, Veria Vacchiano MD, Gianni Sorarù MD, PhD, Eustachio D'Errico MD, PhD, Irene Tramacere MD, PhD, Sara Bortolani MD, Enrica Rolle MD, Cinzia Gellera, Riccardo Zanin, Mauro Silvestrini MD, Luisa Politano, Angelo Schenone MD, Stefano Carlo Previtali MD, PhD, Angela Berardinelli MD, Mara Turri MD, Lorenzo Verriello MD, Michela Coccia MD, Renato Mantegazza MD, Rocco Liguori MD, Massimiliano Filosto MD, PhD, Maria Antonietta Maioli MD, Isabella Laura Simone MD, Tiziana Mongini MD, Stefania Corti MD, PhD, Maria Laura Manca PhD, Elena Pegoraro MD, PhD, Gabriele Siciliano MD, PhD, Giacomo Pietro Comi MD, Lorenzo Maggi MD

Introduction/Aims Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3.

Methods We conducted a multicenter retrospective cohort study, including adult ambulant patients with SMA3, data available on 6-minute walk test (6MWT) and Hammersmith Functional Motor Scale—Expanded (HFMSE) at baseline and at least at 6months of treatment with nusinersen. We investigated fatigability, estimated as 10% or higher decrease in walked distance between the first and sixth minute of the 6MWT, at baseline and over the 14-month follow-up.

Results Forty-eight patients (56% females) were included. The 6MWT improved after 6, 10, and 14months of treatment (p<0.05). Of the 27 patients who completed the entire follow-up, 37% improved (6MWT distance increase =/+30m), 48.2% remained stable, and 14.8% worsened (6MWT distance decline =/+30?m). Fatigability was found at baseline in 26/38 (68%) patients and confirmed at subsequent time points (p<0.05) without any significant change over the treatment period. There was no correlation between fatigability and SMN2 copy number, sex, age at disease onset, age at baseline, nor with 6MWT total distance and baseline HFMSE score.

Discussion Fatigability was detected at baseline in approximately 2/3 of SMA3 walker patients, without any correlation with clinical features, included motor performance. No effect on fatigability was observed during the 14-month treatment period with nusinersen.

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