Clinical and Electrophysiological Changes in Pediatric Spinal Muscular Atrophy after 2 Years of Nusinersen Treatment

Abstract

In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p < 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p < 0.0001) and correlated with treatment yield. A strong negative correlation (r = −0.633) was observed for SMA type 1 and a very strong negative correlation (r = −0.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome.