Brain Morphological Alterations in Adults with Spinal Muscular Atrophy Types 2 and 3: A CAT12-Derived Region-Based and Surface-Based Morphometry Study.

Background/

Objectives

Spinal muscular atrophy (SMA) types 2 and 3 are increasingly recognised as potentially multisystem disorders that may involve the central nervous system. However, the extent and pattern of brain structural alterations in adults remain insufficiently characterised. This study aimed to assess brain morphology in adult patients with SMA using Computational Anatomy Toolbox 12 (CAT12)-derived region-based morphometry and surface-based morphometry.

Methods

The study included 27 right-handed adult patients with SMA types 2 and 3 and 27 age- and sex-matched healthy controls. MRI examinations were performed before initiation of disease-modifying therapy or during the early loading phase of intrathecal nusinersen treatment, with a maximum exposure of two months and no more than three doses before MRI. The groups did not differ significantly in age, sex distribution, or total intracranial volume. Regional volumetric measures and cortical surface-based parameters were extracted from predefined atlas-based regions of interest. Between-group differences and associations with selected clinical and genetic variables were analysed. p-values were corrected for multiple comparisons using the Benjamini-Hochberg false discovery rate procedure.

Results

CAT12-derived region-based morphometry showed a significant reduction in grey matter volume in the left thalamus in patients with SMA compared with healthy controls. Surface-based morphometry revealed increased sulcal depth in the left orbital sulcus as the only cortical finding that remained significant after correction for multiple comparisons. Additional differences in cortical thickness and sulcal depth were observed only at nominal or exploratory thresholds and did not survive correction for multiple comparisons.

Conclusions

Adults with SMA types 2 and 3 showed selected brain structural alterations, particularly reduced grey matter volume in the left thalamus and increased sulcal depth in the left orbital sulcus. These findings are consistent with the concept that SMA may extend beyond lower motor neuron degeneration. Larger longitudinal multimodal studies are warranted to validate these observations and clarify their clinical significance.