The objective of this study was the longitudinal and multimodal description of a cohort of SMA type III and IV patients for the identification of possible biomarkers of disease progression.

Spinal muscular atrophy (SMA) is an autosomal recessive lower motor neuron disease. SMA type III and IV are adult slowly progressing forms.

15 type III and IV adult SMA patients were enrolled in the study. They underwent quantitative muscle force testing, functional evaluation through the SMAFRS and the MFM scales and MUNIX evaluation in 5 (APB, ADM, deltoid, tibialis anterior and trapezius). A composite MUNIX index was calculated by adding the individual values of the 5 muscle.

Participating subjects also underwent spinal cord (SC) MRI. Structural measures of grey (GM) and white matter (WM) involvement and diffusion parameters of WM integrity were evaluated.

The same evaluation protocol was performed at baseline and after 24-months observation time.

Neuromuscular evaluation: Significant modifications over time were observed for the SMAFRS (p = 0.011) and for the MFM3 subscale (p = 0.04). No significant modifications were observed in muscle force.

Neuroimaging: No significant difference was observed in GM and WM cross-sectional area nor in DTI parameters between the baseline and the follow-up evaluation.

Neurophysiology: A significant reduction between the two time-points was observed in the MUNIX for the ADM (p = 0.0005, -23,9%), the trapezius (p = 0.034, -17,43%) and the TA muscle (p = 0.028, -13,9%) as well as in the MUNIX total score (p = 0.0005, -13,32%).

Functional outcomes and MUNIX evaluation can detect disease progression in slow progressive type III and IV adult SMA patients, with MUNIX seeming to be the most sensitive biomarker. The constitution of a composite multimodal score could further increase the ability to predict modification over time.