TY  - JOUR
AU  - Lindig, Tobias
AU  - Bender, Benjamin
AU  - Hauser, Till-Karsten
AU  - Mang, Sarah
AU  - Schweikardt, Daniel
AU  - Klose, Uwe
AU  - Karle, Kathrin N
AU  - Schüle, Rebecca
AU  - Schöls, Ludger
AU  - Rattay, Tim W
TI  - Gray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations.
JO  - Journal of neurology
VL  - 262
IS  - 8
SN  - 0340-5354
CY  - Berlin
PB  - Springer73057
M1  - DZNE-2020-04387
SP  - 1961-1971
PY  - 2015
AB  - Hereditary spastic paraplegias (HSP) are a group of clinically and genetically heterogeneous disorders with the hallmark of progressive spastic gait disturbance. We used advanced neuroimaging to identify brain regions involved in SPG4, the most common HSP genotype. Additionally, we analyzed correlations between imaging and clinical findings. We performed 3T MRI scans including isotropic high-resolution 3D T1, T2-FLAIR, and DTI sequences in 15 adult patients with genetically confirmed SPG4 and 15 age- and sex-matched healthy controls. Brain volume loss of gray and white matter was evaluated through voxel-based morphometry (VBM) for supra- and infratentorial regions separately. DTI maps of axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), and measured anisotropy (MA1) were analyzed through tract-based special statistics (TBSS). VBM and TBSS revealed a widespread affection of gray and white matter in SPG4 including the corpus callosum, medio-dorsal thalamus, parieto-occipital regions, upper brainstem, cerebellum, and corticospinal tract. Significant correlations with correlation coefficients r > 0.6 between clinical data and DTI findings could be demonstrated for disease duration and disease severity as assessed by the spastic paraplegia rating scale for the pontine crossing tract (AD) and the corpus callosum (RD and FA). Imaging also provided evidence that SPG4 underlies a primarily axonal rather than demyelinating damage in accordance with post-mortem data. DTI is an attractive tool to assess subclinical affection in SPG4. The correlation of imaging findings with disease duration and severity suggests AD, RD, and FA as potential progression markers in interventional studies.
KW  - Adult
KW  - Diffusion Tensor Imaging: methods
KW  - Female
KW  - Gray Matter: pathology
KW  - Gray Matter: physiopathology
KW  - Humans
KW  - Magnetic Resonance Imaging: methods
KW  - Male
KW  - Middle Aged
KW  - Severity of Illness Index
KW  - Spastic Paraplegia, Hereditary: pathology
KW  - White Matter: pathology
KW  - White Matter: physiopathology
LB  - PUB:(DE-HGF)16
C6  - pmid:26050637
DO  - DOI:10.1007/s00415-015-7791-7
UR  - https://pub.dzne.de/record/138065
ER  -