Table 2.
Summary of the quantitative neuroimaging findings in Wolfram syndrome patients
| Reference | Neuroimaging findings | Analysis type |
|---|---|---|
| Brain volumes | ||
| Hershey et al. 2012 a | - ↓ Intracranial and whole brain volume | |
| - ↓ brainstem (midbrain, pons, and medulla) volumes; most striking in pons | ROI | |
| - ↓ GM volume in the cerebellum. | VBM | |
| - ↓ WM volume in the cerebellum, brain stem, and subcortex | VBM | |
| Lugar et al. 2016 a | - ↓ total cortical WM and total subcortical GM volumes | |
| - ↓ volume in ventral and dorsal pons, midbrain, medulla, cerebellar WM and GM, thalamus and pallidum | ROI | |
| - ↑ amygdala volume | ROI | |
| Lugar et al. 2019 a | - WM volumes were stable (OR) or decreasing (brainstem and ventral pons) | ROI, VBM |
| - GM volumes were decreasing in thalamus and cerebellar cortex | ROI, VBM | |
| Cortical thickness/cortical volumes | ||
| Hershey et al. 2012 | - ↓ cortical thickness in pre-central region, lingual region, and two rostral middle frontal region | |
| Lugar et al. 2016 | - ↓ cortical thickness and cortical volume in primary and secondary visual cortex; higher cortical volume and surface area in the primary and secondary auditory cortex | ROI |
| - ↓ peri-calcarine region surface area, thickness, and volume; ↓ volume in parahippocampal region; ↑ temporal lobe regions surface area and volume; ↑ rostral middle frontal volume and thickness | QDEC vertex-wise cortical metrics | |
| Diffusion MRI and white matter integrity | ||
| Hershey et al. 2012 | - ↓ FA in the cerebellum and OR + ↓ MD in the cerebellum | ROI |
| - Widespread ↓ FA and AD, mostly in the brainstem, cerebellum and OR | TBSS | |
| Lugar et al. 2016 | - ↓ FA and ↑ RD in OR, MCP, IFOF, and AR; and ↑ AD in OR | Tractography |
| - ↓ FA (CST, IFOF, OR, CC); ↑ RD (MCP, CST, ILF, OR, SLF); ↑ AD (MCP, IFOF, ILF, ALIC) | TBSS | |
a Participants enrolled in these three studies overlap (Hershey et al. 2012: 11 Wolfram patient/ 54 type 1 diabetes and healthy controls; Lugar et al. 2016: 21 Wolfram patients/ 50 type 1 diabetes and healthy controls; Lugar et al. 2019: 29 Wolfram patients/ 52 type 1 diabetes and healthy controls)
GM gray matter, WM white matter, ROI region-of-interest, VBM voxel-based morphometry, QDEC Query, Design, Estimate, Contrast, FA Fractional anisotropy, OR optic radiation, MD mean diffusivity, AD axial diffusivity, RD radial diffusivity, TBSS tract-based spatial statistics, MCP middle cerebellar peduncle, IFOF inferior fronto-occipital fasciculus, AR acoustic radiation, CC corpus callosum, CST corticospinal tract, ILF inferior longitudinal fasciculus, SLF superior longitudinal fasciculus, ALIC anterior limb of internal capsule