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000138065 1001_ $$0P:(DE-HGF)0$$aLindig, Tobias$$b0
000138065 245__ $$aGray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations.
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000138065 520__ $$aHereditary spastic paraplegias (HSP) are a group of clinically and genetically heterogeneous disorders with the hallmark of progressive spastic gait disturbance. We used advanced neuroimaging to identify brain regions involved in SPG4, the most common HSP genotype. Additionally, we analyzed correlations between imaging and clinical findings. We performed 3T MRI scans including isotropic high-resolution 3D T1, T2-FLAIR, and DTI sequences in 15 adult patients with genetically confirmed SPG4 and 15 age- and sex-matched healthy controls. Brain volume loss of gray and white matter was evaluated through voxel-based morphometry (VBM) for supra- and infratentorial regions separately. DTI maps of axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), and measured anisotropy (MA1) were analyzed through tract-based special statistics (TBSS). VBM and TBSS revealed a widespread affection of gray and white matter in SPG4 including the corpus callosum, medio-dorsal thalamus, parieto-occipital regions, upper brainstem, cerebellum, and corticospinal tract. Significant correlations with correlation coefficients r > 0.6 between clinical data and DTI findings could be demonstrated for disease duration and disease severity as assessed by the spastic paraplegia rating scale for the pontine crossing tract (AD) and the corpus callosum (RD and FA). Imaging also provided evidence that SPG4 underlies a primarily axonal rather than demyelinating damage in accordance with post-mortem data. DTI is an attractive tool to assess subclinical affection in SPG4. The correlation of imaging findings with disease duration and severity suggests AD, RD, and FA as potential progression markers in interventional studies.
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000138065 650_2 $$2MeSH$$aAdult
000138065 650_2 $$2MeSH$$aDiffusion Tensor Imaging: methods
000138065 650_2 $$2MeSH$$aFemale
000138065 650_2 $$2MeSH$$aGray Matter: pathology
000138065 650_2 $$2MeSH$$aGray Matter: physiopathology
000138065 650_2 $$2MeSH$$aHumans
000138065 650_2 $$2MeSH$$aMagnetic Resonance Imaging: methods
000138065 650_2 $$2MeSH$$aMale
000138065 650_2 $$2MeSH$$aMiddle Aged
000138065 650_2 $$2MeSH$$aSeverity of Illness Index
000138065 650_2 $$2MeSH$$aSpastic Paraplegia, Hereditary: pathology
000138065 650_2 $$2MeSH$$aWhite Matter: pathology
000138065 650_2 $$2MeSH$$aWhite Matter: physiopathology
000138065 7001_ $$0P:(DE-HGF)0$$aBender, Benjamin$$b1
000138065 7001_ $$0P:(DE-HGF)0$$aHauser, Till-Karsten$$b2
000138065 7001_ $$0P:(DE-HGF)0$$aMang, Sarah$$b3
000138065 7001_ $$0P:(DE-HGF)0$$aSchweikardt, Daniel$$b4
000138065 7001_ $$0P:(DE-HGF)0$$aKlose, Uwe$$b5
000138065 7001_ $$0P:(DE-2719)9000150$$aKarle, Kathrin N$$b6$$udzne
000138065 7001_ $$0P:(DE-2719)2812018$$aSchüle, Rebecca$$b7$$udzne
000138065 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b8$$eCorresponding author$$udzne
000138065 7001_ $$0P:(DE-2719)2811827$$aRattay, Tim W$$b9$$eLast author$$udzne
000138065 77318 $$2Crossref$$3journal-article$$a10.1007/s00415-015-7791-7$$bSpringer Science and Business Media LLC$$d2015-06-09$$n8$$p1961-1971$$tJournal of Neurology$$v262$$x0340-5354$$y2015
000138065 773__ $$0PERI:(DE-600)1421299-7$$a10.1007/s00415-015-7791-7$$gVol. 262, no. 8, p. 1961 - 1971$$n8$$p1961-1971$$q262:8<1961 - 1971$$tJournal of neurology$$v262$$x0340-5354$$y2015
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