Journal Article

DZNE-2020-04387

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Gray and white matter alterations in hereditary spastic paraplegia type SPG4 and clinical correlations.

Lindig, T. ; Bender, B. ; Hauser, T.-K. ; Mang, S. ; Schweikardt, D. ; Klose, U. ; Karle, K. N.DZNE* ; Schüle, R.DZNE* ; Schöls, L. (Corresponding author)DZNE* ; Rattay, T. W. (Last author)DZNE*

2015
Springer73057 Berlin

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Please use a persistent id in citations: doi:10.1007/s00415-015-7791-7

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.

Keyword(s): Adult (MeSH) ; Diffusion Tensor Imaging: methods (MeSH) ; Female (MeSH) ; Gray Matter: pathology (MeSH) ; Gray Matter: physiopathology (MeSH) ; Humans (MeSH) ; Magnetic Resonance Imaging: methods (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Severity of Illness Index (MeSH) ; Spastic Paraplegia, Hereditary: pathology (MeSH) ; White Matter: pathology (MeSH) ; White Matter: physiopathology (MeSH)

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Contributing Institute(s):

1. Ext Hertie-Institut für klinische Hirnforschung (Ext HIH)
2. Functional Neurogeriatrics (AG Maetzler)
3. Clinical Neurogenetics (AG Schöls)
4. Parkinson Genetics (AG Gasser)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2015

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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