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@ARTICLE{Lindig:138065,
      author       = {Lindig, Tobias and Bender, Benjamin and Hauser,
                      Till-Karsten and Mang, Sarah and Schweikardt, Daniel and
                      Klose, Uwe and Karle, Kathrin N and Schüle, Rebecca and
                      Schöls, Ludger and Rattay, Tim W},
      title        = {{G}ray and white matter alterations in hereditary spastic
                      paraplegia type {SPG}4 and clinical correlations.},
      journal      = {Journal of neurology},
      volume       = {262},
      number       = {8},
      issn         = {0340-5354},
      address      = {Berlin},
      publisher    = {Springer73057},
      reportid     = {DZNE-2020-04387},
      pages        = {1961-1971},
      year         = {2015},
      abstract     = {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.},
      keywords     = {Adult / Diffusion Tensor Imaging: methods / Female / Gray
                      Matter: pathology / Gray Matter: physiopathology / Humans /
                      Magnetic Resonance Imaging: methods / Male / Middle Aged /
                      Severity of Illness Index / Spastic Paraplegia, Hereditary:
                      pathology / White Matter: pathology / White Matter:
                      physiopathology},
      cin          = {Ext HIH / AG Maetzler / AG Schöls / AG Gasser},
      ddc          = {610},
      cid          = {I:(DE-2719)5000057 / I:(DE-2719)5000024 /
                      I:(DE-2719)5000005 / I:(DE-2719)1210000},
      pnm          = {344 - Clinical and Health Care Research (POF3-344) / 345 -
                      Population Studies and Genetics (POF3-345)},
      pid          = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-345},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:26050637},
      doi          = {10.1007/s00415-015-7791-7},
      url          = {https://pub.dzne.de/record/138065},
}