Glymphatic Dysfunction in Children With Type 2 and 3 Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) not only causes lower motor neuron degeneration but also affects brain development. Given the role of the glymphatic system in maintaining brain homeostasis during development, this study explores glymphatic changes in children with type 2 and 3 SMA.

Forty-eight children with SMA and 53 age- and sex-matched typically developing (TD) controls were prospectively recruited. A subgroup of 22 patients received nusinersen for one year. Glymphatic function was measured using diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, frequency of enlarged perivascular space (ePVS), and the coupling strength of global blood-oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) dynamics. Based on the data distribution, these parameters were compared using a two-sample t-test or Mann-Whitney U test, followed by False Discovery Rate (FDR) correction. Partial correlation analysis examined the associations between these parameters and clinical severity.

Compared to TD children, SMA children exhibited increased CSF volume, higher ePVS frequency, and a lower ALPS index. CSF volume was negatively correlated with SMA severity. Post-treatment SMA patients showed increased CSF and a lower ALPS index.

This study revealed glymphatic dysfunction in SMA and its correlation with clinical severity, highlighting a previously unrecognized feature of the disease.