The spinal and cerebral profile of adult spinal-muscular atrophy: A multimodal imaging study

Abstract

Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging.

Methods: Twenty-five type III and IV adult SMA patients and 25 age-matched healthy controls were enrolled in a spinal cord and brain imaging study. Structural measures of grey and white matter involvement and diffusion parameters of white matter integrity were evaluated at each cervical spinal level. Whole-brain and region-of-interest analyses were also conducted in the brain to explore cortical thickness, grey matter density and tract-based white matter alterations.

Results: In the spinal cord, considerable grey matter atrophy was detected between C2-C6 vertebral levels. In the brain, increased grey matter density was detected in motor and extra-motor regions of SMA patients. No white matter pathology was identified neither at brain and spinal level.

Conclusions: Adult forms of SMA are associated with selective grey matter degeneration in the spinal cord with preserved white matter integrity. The observed increased grey matter density in the motor cortex may represent adaptive reorganisation.

Keywords: Grey matter and white matter degeneration; Multimodal MRI; SMA; Spinal cord MRI; Spinal muscular atrophy.

Fig. 1

Segmentation and vertebral labelling of cervical spinal cord MRI images. Automated spinal cord segmentation and vertebral labelling on sagittal (a) and axial (b) T2-weighted images resulting in cross-sectional area estimations (mm²). c: sample T2*-weighted images with high GM/WM contrast enabling grey-white matter segmentation and cross-sectional area calculation (mm²).

Fig. 2

The spinal cord atrophy profile of SMA patients. a: Total cross-sectional area values for each vertebral level presented as mean, standard deviation and comparative p-values between SMA patients and healthy controls. b: Grey matter cross-sectional area for each vertebral level presented as mean, standard deviation and comparative p-value between SMA patients and healthy controls c: Visual representation of grey matter atrophy profile of SMA patients expressed as mean CSA and relative standard deviation. CSA = cross-sectional area (mm2) Green colour indicates healthy controls and blue colour indicates the grey matter profile of SMA patients. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Graphical representation of total CSA, GM and WM-CSA for each vertebral level. CSA is measured in mm². Significant differences are indicated by asterisks. Green colour indicates healthy controls, red colour depicts the spinal cord profile of patients with SMA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Increased grey matter density in SMA patients described by voxel-based-morphometry. (A) Increased grey matter density in SMA patients compared to healthy controls at p < .05 FWE (TFCE, age and gender corrections) identified by VBM. MNI coordinates are provided for the relevant axial, sagittal and coronal views. (B) Region of interest (ROI) morphometry in the motor cortex (yellow) highlights a focus of increased grey matter density in SMA patients compared to controls at p < .05 FWE TFCE. MNI coordinates of the focus (red) are indicated on the right bottom corner of the figure. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Comparison of ROI-defined grey and white matter metrics between SMA patients and healthy controls. Boxplots represent raw data in controls (green) and SMA patients (orange). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)